bluuebunny/crossref_metadata_2025 huggingface dataset:
Current-induced viscoelastic topological unwinding of metastable skyrmion strings
Authors: Kagawa Fumitaka , Oike Hiroshi , Koshibae Wataru , Kikkawa Akiko , Okamura Yoshihiro , Taguchi Yasujiro , Nagaosa Naoto , Tokura Yoshinori
Published: October 2017

In the MnSi bulk chiral magnet, magnetic skyrmion strings of 17 nm in diameter appear in the form of a lattice, penetrating the sample thickness, 10–1000 μm. Although such a bundle of skyrmion strings may exhibit complex soft-matter-like dynamics when starting to move under the influence of a random pinning potential, the details remain highly elusive. Here, we show that a metastable skyrmion-string lattice is subject to topological unwinding under the application of pulsed currents of 3–5 × 106 A m–2 rather than being transported, as evidenced by measurements of the topological Hall effect. The critical current density above which the topological unwinding occurs is larger for a shorter pulse width, reminiscent of the viscoelastic characteristics accompanying the pinning-creep transition observed in domain-wall motion. Numerical simulations reveal that current-induced depinning of already segmented skyrmion strings initiates the topological unwinding. Thus, the skyrmion-string length is an element to consider when studying current-induced motion.
Fault-tolerant interface between quantum memories and quantum processors
Authors: Poulsen Nautrup Hendrik , Friis Nicolai , Briegel Hans J.
Published: October 2017

Topological error correction codes are promising candidates to protect quantum computations from the deteriorating effects of noise. While some codes provide high noise thresholds suitable for robust quantum memories, others allow straightforward gate implementation needed for data processing. To exploit the particular advantages of different topological codes for fault-tolerant quantum computation, it is necessary to be able to switch between them. Here we propose a practical solution, subsystem lattice surgery, which requires only two-body nearest-neighbor interactions in a fixed layout in addition to the indispensable error correction. This method can be used for the fault-tolerant transfer of quantum information between arbitrary topological subsystem codes in two dimensions and beyond. In particular, it can be employed to create a simple interface, a quantum bus, between noise resilient surface code memories and flexible color code processors.
Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche
Authors: Plebanek Michael P. , Angeloni Nicholas L. , Vinokour Elena , Li Jia , Henkin Anna , Martinez-Marin Dalia , Filleur Stephanie , Bhowmick Reshma , Henkin Jack , Miller Stephen D. , Ifergan Igal , Lee Yesung , Osman Iman , Thaxton C. Shad , Volpert Olga V.
Published: October 2017

Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These “non-metastatic” exosomes stimulate an innate immune response through the expansion of Ly6Clow patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages. These events require the induction of the Nr4a1 transcription factor and are dependent on pigment epithelium-derived factor (PEDF) on the outer surface of exosomes. Importantly, exosomes isolated from patients with non-metastatic primary melanomas have a similar ability to suppress lung metastasis. This study thus demonstrates that pre-metastatic tumors produce exosomes, which elicit a broad range of PMo-reliant innate immune responses via trigger(s) of immune surveillance, causing cancer cell clearance at the pre-metastatic niche.
Marine oxygen production and open water supported an active nitrogen cycle during the Marinoan Snowball Earth
Authors: Johnson Benjamin W. , Poulton Simon W. , Goldblatt Colin
Published: October 2017

The Neoproterozoic Earth was punctuated by two low-latitude Snowball Earth glaciations. Models permit oceans with either total ice cover or substantial areas of open water. Total ice cover would make an anoxic ocean likely, and would be a formidable barrier to biologic survival. However, there are no direct data constraining either the redox state of the ocean or marine biological productivity during the glacials. Here we present iron-speciation, redox-sensitive trace element, and nitrogen isotope data from a Neoproterozoic (Marinoan) glacial episode. Iron-speciation indicates deeper waters were anoxic and Fe-rich, while trace element concentrations indicate surface waters were in contact with an oxygenated atmosphere. Furthermore, synglacial sedimentary nitrogen is isotopically heavier than the modern atmosphere, requiring a biologic cycle with nitrogen fixation, nitrification and denitrification. Our results indicate significant regions of open marine water and active biologic productivity throughout one of the harshest glaciations in Earth history.
Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice
Authors: Ishida Naoyuki , Ishihara Yuichi , Ishida Kazuto , Tada Hiroyuki , Funaki-Kato Yoshiko , Hagiwara Makoto , Ferdous Taslima , Abdullah Mohammad , Mitani Akio , Michikawa Makoto , Matsushita Kenji
Published: October 2017

Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer’s disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis-inoculated mice. P. gingivalis LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P. gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.
Towards efficient data exchange and sharing for big-data driven materials science: metadata and data formats
Authors: Ghiringhelli Luca M. , Carbogno Christian , Levchenko Sergey , Mohamed Fawzi , Huhs Georg , Lüders Martin , Oliveira Micael , Scheffler Matthias
Published: October 2017

With big-data driven materials research, the new paradigm of materials science, sharing and wide accessibility of data are becoming crucial aspects. Obviously, a prerequisite for data exchange and big-data analytics is standardization, which means using consistent and unique conventions for, e.g., units, zero base lines, and file formats. There are two main strategies to achieve this goal. One accepts the heterogeneous nature of the community, which comprises scientists from physics, chemistry, bio-physics, and materials science, by complying with the diverse ecosystem of computer codes and thus develops “converters” for the input and output files of all important codes. These converters then translate the data of each code into a standardized, code-independent format. The other strategy is to provide standardized open libraries that code developers can adopt for shaping their inputs, outputs, and restart files, directly into the same code-independent format. In this perspective paper, we present both strategies and argue that they can and should be regarded as complementary, if not even synergetic. The represented appropriate format and conventions were agreed upon by two teams, the Electronic Structure Library (ESL) of the European Center for Atomic and Molecular Computations (CECAM) and the NOvel MAterials Discovery (NOMAD) Laboratory, a European Centre of Excellence (CoE). A key element of this work is the definition of hierarchical metadata describing state-of-the-art electronic-structure calculations.
Large positive correlation between the effective electron mass and the multipolar fluctuation in the heavy-fermion metal Ce1
−

x
La
x
B6
Authors: Jang Dongjin , Portnichenko Pavlo Y. , Cameron Alistair S. , Friemel Gerd , Dukhnenko Anatoliy V. , Shitsevalova Natalya Y. , Filipov Volodymyr B. , Schneidewind Astrid , Ivanov Alexandre , Inosov Dmytro S. , Brando Manuel
Published: October 2017

For the last few decades, researchers have been intrigued by multipolar ordering phenomena and related quantum phase transitions in heavy-fermion Kondo systems. However, a criticality induced by substitution level (x), temperature (T), or magnetic field (B) is poorly understood even in the prototypical material, Ce1−x
La
x
B6, despite a large collection of experimental results is available. In this work, we present T–B, x–T, and x–B phase diagrams of Ce1−x
La
x
B6 (B || [110]). These are completed by investigating heat capacity, magnetocaloric effect (MCE), and elastic neutron scattering. A drastic increase of the Sommerfeld coefficient γ0, which is estimated from the heat capacity down to 0.05 K, is observed with increasing x. The precise T–B phase diagram including a high-entropy region is derived from the MCE analysis in which a knowledge beyond the equilibrium thermodynamics is involved. Finally, the x–B phase diagram at T = 0, which supports the existence of a quantum critical point at x > 0.75, is obtained by the same analysis. A detailed interpretation of phase diagrams strongly indicates positive correlation between the fluctuating multipoles and the effective electron mass.
Silica nanoparticle aggregation in calcite replacement reactions
Authors: Liesegang Moritz , Milke Ralf , Kranz Christine , Neusser Gregor
Published: October 2017

Natural nanoparticles are fundamental building blocks of Earth’s bio- and geosphere. Amorphous silica nanoparticles are ubiquitous in nature, but fundamental knowledge of their interaction mechanisms and role in mineral replacement reactions is limited. Here we show how silica nanoparticles replace Cretaceous calcite bivalve shells in a volume- and texture-preserving process. Electron tomography reveals that mineral replacement transfers calcite crystallographic orientations to twinned photonic crystals composed of face-centered cubic silica sphere stacks. During the face-specific replacement process, silica nanoparticles continuously nucleate, aggregate, and form a lattice of uniform spheres parallel to calcite low-energy facets. We explain the replacement process with a new model that unifies recently proposed, probably universal mechanisms of interface-coupled dissolution-precipitation and aggregation-based crystallization; both key mechanisms in geological processes and nanomaterials design and synthesis.
Violet Light Transmission is Related to Myopia Progression in Adult High Myopia
Authors: Torii Hidemasa , Ohnuma Kazuhiko , Kurihara Toshihide , Tsubota Kazuo , Negishi Kazuno
Published: October 2017

Myopia is increasing worldwide. Although the exact etiology of myopia is unknown, outdoor activity is one of the most important environmental factors for myopia control. We previously reported that violet light (VL, 360–400 nm wavelength), which is abundant in the outdoor environment, suppressed myopia progression for individuals under 20 years of age. However, whether VL is also effective for adult high myopia, which can be sight-threatening, has remained unknown. To investigate the influence of VL for adult myopia, we retrospectively compared the myopic progression and the axial length elongation over five years in adult high myopic patients over 25 years of age after two types (non-VL transmitting and VL transmitting) of phakic intraocular lens (pIOL) implantation. We found that high myopic patients with the non-VL transmitting pIOLs implanted are almost two times more myopic in the change of refraction and four times longer in the change of axial length, compared to those implanted with the VL transmitting pIOLs. This result indicated that the VL transmitting pIOL suppressed myopia progression and axial length elongation compared with the non-VL transmitting one. In conclusion, our study showed the VL possibly has an anti-myopia effect for human adults with high myopia.
A perfusion incubator liver chip for 3D cell culture with application on chronic hepatotoxicity testing
Authors: Yu Fang , Deng Rensheng , Hao Tong Wen , Huan Li , Chan Way Ng , IslamBadhan Anik , Iliescu Ciprian , Yu Hanry
Published: October 2017

Liver chips have been developed to recapitulate in vivo physiological conditions to enhance hepatocyte functions for assessing acute responses to drugs. To develop liver chips that can assess repeated dosing chronic hepatotoxicity, we need to ensure that hepatocyte functions be maintained at constant values over two weeks in stable culture conditions of sterility, temperature, pH, fluidic-flow of culture media and drugs. We have designed a perfusion-incubator-liver-chip (PIC) for 3D cell culture, that assures a tangential flow of the media over the spheroids culture. Rat hepatocyte spheroids constrained between a cover glass and a porous-ultrathin Parylene C membrane experienced optimal mass transfer and limited shear stress from the flowing culture media; maintained cell viability over 24 days. Hepatocyte functions were significantly improved and maintained at constant values (urea, albumin synthesis, and CYP450 enzyme activities) for 14 days. The chip act as an incubator, having 5% CO2 pressure-driven culture-media flow, on-chip heater and active debubbler. It operates in a biosafety cabinet, thus minimizing risk of contamination. The chronic drug response to repeated dosing of Diclofenac and Acetaminophen evaluated in PIC were more sensitive than the static culture control.
Machine learning model for sequence-driven DNA G-quadruplex formation
Authors: Sahakyan Aleksandr B. , Chambers Vicki S. , Marsico Giovanni , Santner Tobias , Di Antonio Marco , Balasubramanian Shankar
Published: October 2017

We describe a sequence-based computational model to predict DNA G-quadruplex (G4) formation. The model was developed using large-scale machine learning from an extensive experimental G4-formation dataset, recently obtained for the human genome via G4-seq methodology. Our model differentiates many widely accepted putative quadruplex sequences that do not actually form stable genomic G4 structures, correctly assessing the G4 folding potential of over 700,000 such sequences in the human genome. Moreover, our approach reveals the relative importance of sequence-based features coming from both within the G4 motifs and their flanking regions. The developed model can be applied to any DNA sequence or genome to characterise sequence-driven intramolecular G4 formation propensities.
Predictors of Liver Fat and Stiffness in Non-Alcoholic Fatty Liver Disease (NAFLD) – an 11-Year Prospective Study
Authors: Lallukka Susanna , Sädevirta Sanja , Kallio Markus T. , Luukkonen Panu K. , Zhou You , Hakkarainen Antti , Lundbom Nina , Orho-Melander Marju , Yki-Järvinen Hannele
Published: October 2017

Liver fat can be non-invasively measured by proton magnetic resonance spectroscopy (1H-MRS) and fibrosis estimated as stiffness using transient elastography (FibroScan). There are no longitudinal data on changes in liver fat in Europids or on predictors of liver stiffness using these methods. We determined liver fat (1H-MRS) and clinical characteristics including features of insulin resistance at baseline and after a median follow-up period of 11.3 (range 7.3–13.4) years in 97 Finnish subjects. Liver stiffness was measured at 11.3 years. Liver fat content decreased by 5% (p < 0.05) over time. Values at baseline and 11.3 years were closely interrelated (r = 0.81, p < 0.001). Baseline liver fat (OR 1.32; 95%CI: 1.15–1.50) and change in BMI (OR 1.67; 95%CI: 1.24–2.25) were independent predictors of liver fat at 11.3 years (AUROC 0.90; 95%CI: 0.83–0.96). Baseline liver fat (AUROC 0.84; 95%CI: 0.76–0.92) predicted liver fat at 11.3 years more accurately than routinely available parameters (AUROC 0.76; 95%CI: 0.65–0.86, p = 0.02). At 11.3 years, 29% of the subjects had increased liver stiffness. Baseline liver fat (OR 2.17; 95%CI: 1.05–4.46) was an independent predictor of increased liver stiffness. These data show that liver fat is more important than the associated metabolic abnormalities as the predictor of future liver fat and fibrosis.
Candidate proteins from predegenerated nerve exert time-specific protection of retinal ganglion cells in glaucoma
Authors: Pietrucha-Dutczak Marita , Smedowski Adrian , Liu Xiaonan , Matuszek Iwona , Varjosalo Markku , Lewin-Kowalik Joanna
Published: October 2017

Glaucoma is thought to be the main cause of severe visual impairment or permanent loss of vision. Current therapeutic strategies are not sufficient to protect against glaucoma. Thus, new therapies and potential novel therapeutic targets must be developed to achieve progress in the treatment of this insidious disease. This study was undertaken to verify whether the time of administration of an extract from predegenerated rat sciatic nerves as well as exposure time of this extract onto retinal ganglion cells (RGCs) influences the survival of RGCs in a rat glaucoma model. We have demonstrated that extract obtained from the predegenerated sciatic nerves protects RGCs in a rat glaucoma model. The neuroprotective effect depends mostly on the time of administration of the extract and less clearly on the time of exposure to the extract and is associated with stimulation of endogenous BDNF expression both in RGCs and glial cells. The 14th day following glaucoma induction represents a therapeutic window for effective treatment in a glaucoma model. Mass Spectrometry analysis demonstrated that metallothionein 2 (MT2) may be a key molecule responsible for neuroprotective effects on RGC survival.
Numerical Investigation of Tunable Plasmonic Tweezers based on Graphene Stripes
Authors: Samadi Mohsen , Darbari Sara , Moravvej-Farshi Mohammad Kazem
Published: October 2017

We are proposing tunable plasmonic tweezers, consisting two parallel graphene stripes, which can be utilized to effectively trap and sort nanoparticles. We show that by electrostatically tuning the chemical potential of a graphene stripe by about 100 meV (equivalent to ΔVG ≈ 4.4 V), the plasmonic force can be switched efficiently, without a need to switch the laser intensity. This enables high speed and low power switching with a large number of switching cycles. By applying two independent and appropriate gate bias voltages to the stripes, the direction of the plasmonic force can be reversed, which leads to separation of nanoparticles that satisfy the trapping conditions. Numerical simulations show that the potential depths obtained for polystyrene nanoparticles of refractive index n = 1.5717 and radii r ≥ 50 nm is deeper than −10 kBT , confirming the ability of the proposed system to effectively separate such nanoparticles. This capability holds for smaller nanoparticles with larger refractive indices. Finally, performing thermal simulations, we have demonstrated that the heat induced by the illumination increases the fluid temperature by at most 9 °C, having negligible effect on the trapping mechanism. The proposed system opens up new possibilities in developing tunable on-chip manipulation devices, suitable for biological applications.
Identification of unusual peptides with new Cys frameworks in the venom of the cold-water sea anemone Cnidopus japonicus
Authors: Babenko Vladislav V. , Mikov Alexander N. , Manuvera Valentin A. , Anikanov Nickolay A. , Kovalchuk Sergey I. , Andreev Yaroslav A. , Logashina Yulia A. , Kornilov Daniil A. , Manolov Alexander I. , Sanamyan Nadya P. , Sanamyan Karen E. , Kostryukova Elena S. , Kozlov Sergey A. , Grishin Eugene V. , Govorun Vadim M. , Lazarev Vassili N.
Published: October 2017

Sea anemones (Actiniaria) are intensely popular objects of study in venomics. Order Actiniaria includes more than 1,000 species, thus presenting almost unlimited opportunities for the discovery of novel biologically active molecules. The venoms of cold-water sea anemones are studied far less than the venoms of tropical sea anemones. In this work, we analysed the molecular venom composition of the cold-water sea anemone Cnidopus japonicus. Two sets of NGS data from two species revealed molecules belonging to a variety of structural classes, including neurotoxins, toxin-like molecules, linear polypeptides (Cys-free), enzymes, and cytolytics. High-throughput proteomic analyses identified 27 compounds that were present in the venoms. Some of the toxin-like polypeptides exhibited novel Cys frameworks. To characterise their function in the venom, we heterologously expressed 3 polypeptides with unusual Cys frameworks (designated CjTL7, CjTL8, and AnmTx Cj 1c-1) in E. coli. Toxicity tests revealed that the CjTL8 polypeptide displays strong crustacean-specific toxicity, while AnmTx Cj 1c-1 is toxic to both crustaceans and insects. Thus, an improved NGS data analysis algorithm assisted in the identification of toxins with unusual Cys frameworks showing no homology according to BLAST. Our study shows the advantage of combining omics analysis with functional tests for active polypeptide discovery.
Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis
Authors: Wang Neng , Zheng Yifeng , Gu Jiangyong , Cai Youli , Wang Shengqi , Zhang Fengxue , Chen Jianping , Situ Honglin , Lin Yi , Wang Zhiyu
Published: October 2017

Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer. In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model. The herb-ingredient-target network analysis further identified a total of 81 genes closely correlated with the breast cancer chemoprevention effects of XIAOPI. Cytokine array analysis further validated CXCL-1 as the key target of XIAOPI both in vitro and in vivo. Evaluation of the mechanism demonstrated that CXCL-1 administration significantly abrogated the metastatic inhibition effects of XIAOPI on breast cancer migration, invasion, stem cells subpopulations, epithelial-mesenchymal transition(EMT), or mammosphere formation abilities. Overall, our study provides experimental evidence and molecular mechanisms that may facilitate the safe and effective use of herbal medicine for the prevention of breast cancer growth or metastasis, and may lead to CXCL-1-based therapeutic strategies for mammary malignancies.
Penicillin induces alterations in glutamine metabolism in Streptococcus pneumoniae
Authors: El Khoury Jessica Y. , Boucher Nancy , Bergeron Michel G. , Leprohon Philippe , Ouellette Marc
Published: October 2017

Penicillin is a bactericidal antibiotic that inhibits the synthesis of the peptidoglycan by targeting penicillin-binding proteins. This study aimed to assess through transcriptional profiling the stress response of S. pneumoniae strains after exposure to lethal penicillin concentrations to understand further the mode of action of penicillin. Two experimental designs (time-course and dose-response) were used for monitoring the effect of penicillin on the transcriptional profile. The expression of some genes previously shown to be modulated by penicillin was altered, including ciaRH, pstS and clpL. Genes of the glnRA and glnPQ operons were among the most downregulated genes in the three strains. These genes are involved in glutamine synthesis and uptake and LC-MS work confirmed that penicillin treatment increases the intracellular glutamine concentrations. Glutamine conferred a protective role against penicillin when added to the culture medium. Glutamine synthetase encoded by glnA catalyses the transformation of glutamate and ammonium into glutamine and its chemical inhibition by the inhibitor L-methionine sulfoximine is shown to sensitize S. pneumoniae to penicillin, including penicillin-resistant clinical isolates. In summary, a combination of RNA-seq and metabolomics revealed that penicillin interferes with glutamine metabolism suggesting strategies that could eventually be exploited for combination therapy or for reversal of resistance.
The comprehensive expression analysis of circular RNAs in gastric cancer and its association with field cancerization
Authors: Vidal Amanda Ferreira , Ribeiro-dos-Santos André M. , Vinasco-Sandoval Tatiana , Magalhães Leandro , Pinto Pablo , Anaissi Ana K. M. , Demachki Samia , de Assumpção Paulo Pimentel , dos Santos Sidney Emanuel Batista , Ribeiro-dos-Santos Ândrea
Published: October 2017

Circular RNAs comprise a new class of long noncoding RNAs characterized by their 5′ and 3′ ends covalently joined. Previous studies have demonstrated that some circular RNAs act as microRNA sponges, and are associated with cellular proliferation in cancer. We were the first to analyze the global expression of circular RNAs in samples of patients without gastric cancer, gastric cancer, and matched tumor-adjacent gastric tissue. Among the samples, we identified 736 previously annotated circular RNAs by RNA-Seq. The tumor-adjacent tissue presented the higher abundance of circular RNAs and could not be considered as a normal tissue, reinforcing the notion of field effect in gastric cancer. We identified five differentially expressed circular RNAs that may be potential biomarkers of this type of cancer. We also predicted candidate microRNAs targets of the highest expressed circular RNAs in gastric tissues and found five miRNAs. Overall, our results support the hypothesis of circular RNAs representing a novel factor in the dynamic epigenetic network of gene regulation, which involves the microRNAs, its mRNAs targets, and the circular RNAs-derived genes. Further studies are needed to elucidate the roles and the functional relevance of the circular RNAs in human diseases.
Centimeter-wide worm-like fossils from the lowest Cambrian of South China
Authors: Zhang Xingliang , Liu Wei , Isozaki Yukio , Sato Tomohiko
Published: October 2017

The trace fossil record implies that large worm-like animals were in place along with the skeletonizing organisms during the initial stage of the Cambrian explosion. Body fossils of large worms, however, have so far not been found. Here, we describe a large, soft-bodied, worm-like organism, Vittatusivermis annularius gen. et sp. nov. from the lowest Cambrian of South China, which is constrained to the Fortunian Age (541–529 Ma) of the Cambrian Period. The elongate body of Vittatusivermis was large enough to have supported organ systems and a fluid skeleton that facilitated peristaltic locomotion, thus allowing for more complex patterns of movement than those of flatworms. Its occurrence on the same bedding surface as trace fossils suggests that Vittatusivermis might have produced epichnial trails and shallow burrows on and within sediments. Therefore, Vittatusivermis is likely to have been one of the long expected producers of trace fossils in the earliest Cambrian.
Identification of claudin-4 binder that attenuates tight junction barrier function by TR-FRET-based screening assay
Authors: Watari Akihiro , Kodaka Miki , Matsuhisa Koji , Sakamoto Yuta , Hisaie Kota , Kawashita Norihito , Takagi Tatsuya , Yamagishi Yoshiaki , Suzuki Hidehiko , Tsujino Hirofumi , Yagi Kiyohito , Kondoh Masuo
Published: October 2017

Claudins are key functional and structural components of tight junctions (TJs) in epithelial cell sheets. The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) binds to claudin-4 and reversibly modulates intestinal TJ seals, thereby enhancing paracellular transport of solutes. However, the use of C-CPE as an absorption enhancer is limited by the molecule’s immunogenicity and manufacturing cost. Here, we developed a high-throughput screening system based on the Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) method to identify claudin-4 binders in a library collection of 32,560 compounds. Thiostrepton, identified from the screen, decreased transepithelial electrical resistance and increased flux of 4-kDa fluorescein isothiocyanate–labelled dextran (FD-4) in Caco-2 cell monolayers, a model of intestinal epithelium. Thiostrepton changed the expression, but not the localisation, of TJ components. Treatment of rat jejunum with thiostrepton increased the absorption of FD-4 without tissue toxicity, indicating that thiostrepton is a novel claudin-4 binder that enhances intestinal permeability. The screening system may therefore be a useful tool for identifying claudin-4 binders to enhance drug absorption in mucosa.
A role for small secreted proteins (SSPs) in a saprophytic fungal lifestyle: Ligninolytic enzyme regulation in Pleurotus ostreatus
Authors: Feldman Daria , Kowbel David J. , Glass N. Louise , Yarden Oded , Hadar Yitzhak
Published: October 2017

Small secreted proteins (SSPs), along with lignocellulose degrading enzymes, are integral components of the secretome ofPleurotus ostreatus, a white rot fungus. In this study, we identified 3 genes (ssp1,2and3) encoding proteins that are annotated as SSPs and that exhibited of ~4,500- fold expression, 24 hr following exposure to the toxic compound 5-hydroxymethylfurfural (HMF). Homologues to genes encoding these SSPs are present in the genomes of other basidiomycete fungi, however the role of SSPs is not yet understood. SSPs, aryl-alcohol oxidases (AAO) and the intracellular aryl-alcohol dehydrogenases (AAD) were also produced after exposure to other aryl-alcohols, known substrates and inducers of AAOs, and during idiophase (after the onset of secondary metabolism). A knockdown strain ofssp1exhibited reduced production of AAO-and AAD-encoding genes after HMF exposure. Conversely, a strain overexpressingssp1exhibited elevated expression of genes encoding AAOs and ADD, resulting in a 3-fold increase in enzymatic activity of AAOs, as well as increased expression and protein abundance of versatile peroxidase 1, which directly degrades lignin. We propose that in addition to symbionts and pathogens, SSPs also have roles in saprophytes and function inP. ostreatusas components of the ligninolytic system.
Discovering geothermal supercritical fluids: a new frontier for seismic exploration
Authors: Piana Agostinetti Nicola , Licciardi Andrea , Piccinini Davide , Mazzarini Francesco , Musumeci Giovanni , Saccorotti Gilberto , Chiarabba Claudio
Published: October 2017

Exploiting supercritical geothermal resources represents a frontier for the next generation of geothermal electrical power plant, as the heat capacity of supercritical fluids (SCF),which directly impacts on energy production, is much higher than that of fluids at subcritical conditions. Reconnaissance and location of intensively permeable and productive horizons at depth is the present limit for the development of SCF geothermal plants. We use, for the first time, teleseismic converted waves (i.e. receiver function) for discovering those horizons in the crust. Thanks to the capability of receiver function to map buried anisotropic materials, the SCF-bearing horizon is seen as the 4km-depth abrupt termination of a shallow, thick, ultra-high (>30%) anisotropic rock volume, in the center of the Larderello geothermal field. The SCF-bearing horizon develops within the granites of the geothermal field, bounding at depth the vapor-filled heavily-fractured rock matrix that hosts the shallow steam-dominated geothermal reservoirs. The sharp termination at depth of the anisotropic behavior of granites, coinciding with a 2 km-thick stripe of seismicity and diffuse fracturing, points out the sudden change in compressibility of the fluid filling the fractures and is a key-evidence of deep fluids that locally traversed the supercritical conditions. The presence of SCF and fracture permeability in nominally ductile granitic rocks open new scenarios for the understanding of magmatic systems and for geothermal exploitation.
Enhancing reading performance through action video games: the role of visual attention span
Authors: Antzaka A. , Lallier M. , Meyer S. , Diard J. , Carreiras M. , Valdois S.
Published: October 2017

Recent studies reported that Action Video Game-AVG training improves not only certain attentional components, but also reading fluency in children with dyslexia. We aimed to investigate the shared attentional components of AVG playing and reading, by studying whether the Visual Attention (VA) span, a component of visual attention that has previously been linked to both reading development and dyslexia, is improved in frequent players of AVGs. Thirty-six French fluent adult readers, matched on chronological age and text reading proficiency, composed two groups: frequent AVG players and non-players. Participants performed behavioural tasks measuring the VA span, and a challenging reading task (reading of briefly presented pseudo-words). AVG players performed better on both tasks and performance on these tasks was correlated. These results further support the transfer of the attentional benefits of playing AVGs to reading, and indicate that the VA span could be a core component mediating this transfer. The correlation between VA span and pseudo-word reading also supports the involvement of VA span even in adult reading. Future studies could combine VA span training with defining features of AVGs, in order to build a new generation of remediation software.
Highly Performance Core-Shell TiO2(B)/anatase Homojunction Nanobelts with Active Cobalt phosphide Cocatalyst for Hydrogen Production
Authors: Yang Guang , Ding Hao , Feng Jiejie , Hao Qiang , Sun Sijia , Ao Weihua , Chen Daimei
Published: October 2017

In this paper, a highly efficient core-shell structure of TiO2(B)/anatase photocatalyst with CoP cocatalyst has been synthesized via hydrothermal processes and a mechanical milling method. The designed core-shell TiO2(B)/anatase photocatalysts exhibit excellent performance by compared with pure TiO2(B) and anatase phase. With the participation of CoP particles, there is drastically enhanced  photocatalytic activity of TiO2(B)/anatase, and the H2-production rate can be up to 7400 μmol·g−1, which is about 3.2 times higher than TiO2(B)/anatase photocatalyst. The improved activity is attributed to the contribution of the well-matched core-shell structure and cooperative effect of CoP cocatalyst. The photogenerated holes of anatase can migrate more promptly to the adjacent TiO2(B) core than the photogenerated electrons, which result in an accumulation of electrons in the anatase, and CoP nanoparticles can contribute significantly to transferring electrons from the surface of TiO2(A). It was found that the efficient separation of electron-hole pairs greatly improved the photocatalytic hydrogen evolution in water under UV light irradiation.
8000-year monsoonal record from Himalaya revealing reinforcement of tropical and global climate systems since mid-Holocene
Authors: Srivastava Pradeep , Agnihotri Rajesh , Sharma Deepti , Meena Narendra , Sundriyal Y. P. , Saxena Anju , Bhushan Ravi , Sawlani R. , Banerji Upasana S. , Sharma C. , Bisht P. , Rana N. , Jayangondaperumal R.
Published: October 2017

We provide the first continuous Indian Summer Monsoon (ISM) climate record for the higher Himalayas (Kedarnath, India) by analyzing a 14C-dated peat sequence covering the last ~8000 years, with ~50 years temporal resolution. The ISM variability inferred using various proxies reveal striking similarity with the Greenland ice core (GISP2) temperature record and rapid denitrification changes recorded in the sediments off Peru. The Kedarnath record provides compelling evidence for a reorganization of the global climate system taking place at ~5.5 ka BP possibly after sea level stabilization and the advent of inter-annual climate variability governed by the modern ENSO phenomenon. The ISM record also captures warm-wet and cold-dry conditions during the Medieval Climate Anomaly and Little Ice Age, respectively.
Neuroprotective effect of Ruminococcus albus on oxidatively stressed SH-SY5Y cells and animals
Authors: Park Jieun , Lee Jiyun , Yeom Zia , Heo Donghyuk , Lim Young-Hee
Published: October 2017

Recent evidence shows that the gut microbiota has an important role in gut-brain crosstalk and is linked to neuronal disorders. The aim of this study was to investigate the effects of intestinal Ruminococcus albus with probiotic potential on neuroprotection in oxidatively stressed SH-SY5Y neuroblastoma cells and animals. To investigate these effects, conditioned medium was prepared using Caco-2 cells cultured with heat-killed R. albus (CRA-CM). Caco-2 cells cultured with heat-killed R. albus showed increased BDNF expression and BDNF protein levels increased in CRA-CM. CRA-CM up-regulated the protein expression levels of SRF, C-fos and CDK2. In addition, CRA-CM protected SH-SY5Y cells from H2O2-induced cell death. CRA-CM significantly decreased the Bax/Bcl-2 ratio in oxidatively stressed SH-SY5Y cells. Animal experiments showed that oral administration of heat-killed R. albus for 15 days attenuated the oxidative stress induced by sodium arsenate. Treatment with heat-killed R. albus reduced the level of ROS, and the levels of SOD and GSH increased in oxidatively stressed brains. In conclusion, the secretome prepared from Caco-2 cells cultured with heat-killed R. albus might promote neuronal proliferation through the activation of cell proliferation-related proteins, and heat-killed R. albus protects neurons from oxidative damage by reducing ROS levels and increasing SOD and GSH levels.
Knockdown of amyloid precursor protein increases calcium levels in the endoplasmic reticulum
Authors: Gazda Kinga , Kuznicki Jacek , Wegierski Tomasz
Published: October 2017

Familial Alzheimer’s disease (AD) is caused by mutations in the genes that encode amyloid precursor protein (APP) and presenilins. Disturbances in calcium homeostasis have been observed in various cellular and animal models of AD and are proposed to underlie the pathogenesis of the disease. Furthermore, wildtype presenilins were shown to regulate endoplasmic reticulum (ER) calcium homeostasis, although their precise mechanism of action remains controversial. To investigate whether APP also affects ER calcium levels, we used RNA interference to target the APP gene in cultured T84 cells in combination with two types of ER calcium sensors. Using a genetically encoded calcium indicator, GEM-CEPIA1er, we found that APP-deficient cells exhibited elevated resting calcium levels in the ER and prolonged emptying of ER calcium stores upon the cyclopiazonic acid-induced inhibition of sarco-endoplasmic reticulum calcium-ATPase. These effects could be ascribed to lower ER calcium leakage rates. Consistent with these results, translocation of the endogenous ER calcium sensor STIM1 to its target channel Orai1 was delayed following ER calcium store depletion. Our data suggest a physiological function of APP in the regulation of ER calcium levels.
A robust single-beam optical trap for a gram-scale mechanical oscillator
Authors: Altin P. A. , Nguyen T. T.-H. , Slagmolen B. J. J. , Ward R. L. , Shaddock D. A. , McClelland D. E.
Published: October 2017

Precise optical control of microscopic particles has been mastered over the past three decades, with atoms, molecules and nano-particles now routinely trapped and cooled with extraordinary precision, enabling rapid progress in the study of quantum phenomena. Achieving the same level of control over macroscopic objects is expected to bring further advances in precision measurement, quantum information processing and fundamental tests of quantum mechanics. However, cavity optomechanical systems dominated by radiation pressure – so-called ‘optical springs’ – are inherently unstable due to the delayed dynamical response of the cavity. Here we demonstrate a fully stable, single-beam optical trap for a gram-scale mechanical oscillator. The interaction of radiation pressure with thermo-optic feedback generates damping that exceeds the mechanical loss by four orders of magnitude. The stability of the resultant spring is robust to changes in laser power and detuning, and allows purely passive self-locking of the cavity. Our results open up a new way of trapping and cooling macroscopic objects for optomechanical experiments.
Prevalence and factors associated with chronic kidney disease and end-stage renal disease in HIV-1-infected Asian patients in Tokyo
Authors: Nishijima Takeshi , Kawasaki Yohei , Mutoh Yoshikazu , Tomonari Kiyomi , Tsukada Kunihisa , Kikuchi Yoshimi , Gatanaga Hiroyuki , Oka Shinichi
Published: October 2017

This single-center cross-sectional study determined the prevalence and factors associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD) in HIV-1-infected Asian patients at the largest HIV clinic in Japan. HIV-1-infected patients who visited the clinic between September and December 2016 were analyzed. CKD was defined as estimated glomerular filtration rate of <60 ml/min/1.73 m2 or proteinuria ≥1+, observed at least over three months. A logistic regression model was used to estimate the effects of various variables on CKD. The study included 1,990 patients; with 97% Asians, 34% aged of ≥50 years, and 94% had HIV-1 load <50 copies/ml. The median time from HIV-1 diagnosis to study enrollment and duration of ART were 9.1 years (IQR4.8–14.2) and 7.35 years (IQR3.28–12), respectively. CKD and ESRD were diagnosed in 256 (13%) and 9 (0.5%) patients, respectively. The prevalence of CKD was 18.6% for age 50–59, 28.5% for 60–69, and 47% for over 70. Older age, heavier body weight, diabetes mellitus, hypertension, and longer duration of ART, but not duration of TDF exposure, were associated with CKD. The traditional risk factors, rather than HIV-1-related variables, were associated with CKD, suggesting the importance of management of such comorbidities in maintenance of renal function.
Selectivity of Cobalt Corrole for CO vs. O2 and N2 in Indoor Pollution
Authors: Sheng Xia , Zhao Hailiang , Du Lin
Published: October 2017

Coal combustion causes indoor pollution of CO. In this work, DFT calculations on cobalt corrole (Co(Cor)) with three most common indoor gas molecules (N2, O2 and CO) were performed. The Mulliken spin densities show that the ground states of Co(N2)(Cor), Co(CO)(Cor) and Co(OC)(Cor) have an anti-ferromagnetic coupling fashion of the electrons on the Co 3d
z
2 orbital and the π orbital of the corrole ring. However, Co(O2)(Cor) has a triplet ground state. With the spin contamination corrections, the Co(N2)(Cor) binding energy was obtained at −50.6 kcal mol−1 (B3LYP-D3). While CO can interact with Co(Cor) in two different ways, and their binding energies were −22.8 and −10.9 kcal mol−1 (B3LYP-D3) for Co(CO)(Cor) and Co(OC)(Cor), respectively. The natural bond orbital charges on the axial ligands (NO, CO, OC) are increased upon the chemical bond formation. These are the cause of the shorten metal-ligand bond and the increase of the wavenumber of the metal-ligand bond vibrational transitions. While the charges for O2 are decreased, leading to bond elongation as well as the decrease of the wavenumber upon complexation. Overall, O2 was found to be hardly coordinated with Co(Cor). This study provides a detailed molecular understanding of interactions between a gas sensor and gaseous indoor air-pollutants.
Chemical Similarity Enrichment Analysis (ChemRICH) as alternative to biochemical pathway mapping for metabolomic datasets
Authors: Barupal Dinesh Kumar , Fiehn Oliver
Published: October 2017

Metabolomics answers a fundamental question in biology: How does metabolism respond to genetic, environmental or phenotypic perturbations? Combining several metabolomics assays can yield datasets for more than 800 structurally identified metabolites. However, biological interpretations of metabolic regulation in these datasets are hindered by inherent limits of pathway enrichment statistics. We have developed ChemRICH, a statistical enrichment approach that is based on chemical similarity rather than sparse biochemical knowledge annotations. ChemRICH utilizes structure similarity and chemical ontologies to map all known metabolites and name metabolic modules. Unlike pathway mapping, this strategy yields study-specific, non-overlapping sets of all identified metabolites. Subsequent enrichment statistics is superior to pathway enrichments because ChemRICH sets have a self-contained size where p-values do not rely on the size of a background database. We demonstrate ChemRICH’s efficiency on a public metabolomics data set discerning the development of type 1 diabetes in a non-obese diabetic mouse model. ChemRICH is available at www.chemrich.fiehnlab.ucdavis.edu
Cytotoxicity of Aconitum alkaloid and its interaction with calf thymus DNA by multi-spectroscopic techniques
Authors: Liu Fei , Tan Xiaoxin , Han Xu , Li Xiang , Li Nan , Kang Weijun
Published: October 2017

The cytotoxicities of three aconitum alkaloids- aconitine, hypaconitine and mesaconitine, and their abilities to bind DNA have been explored. Rat myocardial cells H9c2 were treated with aconitum alkaloids and assessed the cytotoxicities by using MTT assay and flow cytometry. Apoptosis was evidenced by the results of the annexin V/propidium iodide (PI) assay. Aconitine was found to be the most toxic in rat myocardial cells H9c2 in three aconitum alkaloids. At the same time, DNA adducts were isolated and then analyzed by UV-Vis spectroscopy after exposure to alkaloids, which indicated that three alkaloids could bind to DNA in rat myocardial cells H9c2. Furthermore, their binding modes were investigated by UV-Visible, fluorescence, DNA melting studies and ionic strength effect. Results indicated that the interaction between three alkaloids and DNA were intercalation coupled with electrostatic effect. The estimated binding constants were between 4.83 × 105 M−1 to 9.85 × 105 M−1 for three alkaloids at 298 K.