bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults
Authors: Laws Simon M. , Gaskin Scott , Woodfield Amy , Srikanth Velandai , Bruce David , Fraser Paul E. , Porter Tenielle , Newsholme Philip , Wijesekara Nadeeja , Burnham Samantha , Doré Vincent , Li Qiao-Xin , Maruff Paul , Masters Colin L. , Rainey-Smith Stephanie , Rowe Christopher C. , Salvado Olivier , Villemagne Victor L. , Martins Ralph N. , Verdile Giuseppe
Published: August 2017

Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer’s disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippocampal volume and neocortical Aβ-amyloid burden). We reveal that HOMA-IR (p < 0.001) incrementally increases across diagnostic groups, becoming significantly elevated in the AD group compared with cognitively normal (CN) adults. In CN adults, higher HOMA-IR was associated with poorer performance on measures of verbal episodic memory (p = 0.010), executive function (p = 0.046) and global cognition (p = 0.007), as well as with higher CSF T-tau (p = 0.008) and P-tau (p = 0.014) levels. No association was observed with CSF Aβ or imaging modalities. Together our data suggest that IR may contribute to reduced cognitive performance and the accumulation of CSF tau biomarkers in cognitively normal adults.
A time series transcriptome analysis of cassava (Manihot esculenta Crantz) varieties challenged with Ugandan cassava brown streak virus
Authors: Amuge T. , Berger D. K. , Katari M. S. , Myburg A. A. , Goldman S. L. , Ferguson M. E.
Published: August 2017

A time-course transcriptome analysis of two cassava varieties that are either resistant or susceptible to cassava brown streak disease (CBSD) was conducted using RNASeq, after graft inoculation with Ugandan cassava brown streak virus (UCBSV). From approximately 1.92 billion short reads, the largest number of differentially expressed genes (DEGs) was obtained in the resistant (Namikonga) variety at 2 days after grafting (dag) (3887 DEGs) and 5 dag (4911 DEGs). At the same time points, several defense response genes (encoding LRR-containing, NBARC-containing, pathogenesis-related, late embryogenesis abundant, selected transcription factors, chaperones, and heat shock proteins) were highly expressed in Namikonga. Also, defense-related GO terms of ‘translational elongation’, ‘translation factor activity’, ‘ribosomal subunit’ and ‘phosphorelay signal transduction’, were overrepresented in Namikonga at these time points. More reads corresponding to UCBSV sequences were recovered from the susceptible variety (Albert) (733 and 1660 read counts per million (cpm)) at 45 dag and 54 dag compared to Namikonga (10 and 117 cpm respectively). These findings suggest that Namikonga’s resistance involves restriction of multiplication of UCBSV within the host. These findings can be used with other sources of evidence to identify candidate genes and biomarkers that would contribute substantially to knowledge-based resistance breeding.
Characterization of a metabolomic profile associated with responsiveness to therapy in the acute phase of septic shock
Authors: Cambiaghi Alice , Pinto Bernardo Bollen , Brunelli Laura , Falcetta Francesca , Aletti Federico , Bendjelid Karim , Pastorelli Roberta , Ferrario Manuela
Published: August 2017

The early metabolic signatures associated with the progression of septic shock and with responsiveness to therapy can be useful for developing target therapy. The Sequential Organ Failure Assessment (SOFA) score is used for stratifying risk and predicting mortality. This study aimed to verify whether different responses to therapy, assessed as changes in SOFA score at admission (T1, acute phase) and 48 h later (T2, post-resuscitation), are associated with different metabolite patterns. We examined the plasma metabolome of 21 septic shock patients (pts) enrolled in the Shockomics clinical trial (NCT02141607). Patients for which SOFAT2 was >8 and Δ = SOFAT1 − SOFAT2 < 5, were classified as not responsive to therapy (NR, 7 pts), the remaining 14 as responsive (R). We combined untargeted and targeted mass spectrometry-based metabolomics strategies to cover the plasma metabolites repertoire as far as possible. Metabolite concentration changes from T1 to T2 (Δ = T2 − T1) were used to build classification models. Our results support the emerging evidence that lipidome alterations play an important role in individual patients’ responses to infection. Furthermore, alanine indicates a possible alteration in the glucose-alanine cycle in the liver, providing a different picture of liver functionality from bilirubin. Understanding these metabolic disturbances is important for developing any effective tailored therapy for these patients.
AhR-deficiency as a cause of demyelinating disease and inflammation
Authors: Juricek Ludmila , Carcaud Julie , Pelhaitre Alice , Riday Thorfinn T. , Chevallier Aline , Lanzini Justine , Auzeil Nicolas , Laprévote Olivier , Dumont Florent , Jacques Sebastien , Letourneur Frank , Massaad Charbel , Agulhon Cendra , Barouki Robert , Beraneck Mathieu , Coumoul Xavier
Published: August 2017

The Aryl hydrocarbon Receptor(AhR) is among the most important receptors which bind pollutants; however it also regulates signaling pathways independently of such exposure. We previously demonstrated that AhR is expressed during development of the central nervous system(CNS) and that its deletion leads to the occurrence of a congenital nystagmus. Objectives of the present study are to decipher the origin of these deficits, and to identify the role of the AhR in the development of the CNS. We show that the AhR-knockout phenotype develops during early infancy together with deficits in visual-information-processing which are associated with an altered optic nerve myelin sheath, which exhibits modifications in its lipid composition and in the expression of myelin-associated-glycoprotein(MAG), a cell adhesion molecule involved in myelin-maintenance and glia-axon interaction. In addition, we show that the expression of pro-inflammatory cytokines is increased in the impaired optic nerve and confirm that inflammation is causally related with an AhR-dependent decreased expression of MAG. Overall, our findings demonstrate the role of the AhR as a physiological regulator of myelination and inflammatory processes in the developing CNS. It identifies a mechanism by which environmental pollutants might influence CNS myelination and suggest AhR as a relevant drug target for demyelinating diseases.
Enhanced Fluorine-19 MRI Sensitivity using a Cryogenic Radiofrequency Probe: Technical Developments and Ex Vivo Demonstration in a Mouse Model of Neuroinflammation
Authors: Waiczies Sonia , Millward Jason M. , Starke Ludger , Delgado Paula Ramos , Huelnhagen Till , Prinz Christian , Marek Daniel , Wecker Didier , Wissmann Ralph , Koch Stefan P. , Boehm-Sturm Philipp , Waiczies Helmar , Niendorf Thoralf , Pohlmann Andreas
Published: August 2017

Neuroinflammation can be monitored using fluorine-19 (19F)-containing nanoparticles and 19F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) 19F radiofrequency (RF) coils and low spatial resolution 19F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions. Here we used a new 19F transceive cryogenic quadrature RF probe (
19
F-CRP) that provides the SNR necessary to acquire superior spatially-resolved 19F MRI. First we characterized the signal-transmission profile of the
19
F-CRP. The
19
F-CRP was then benchmarked against a RT 19F/1H RF coil. For SNR comparison we used reference compounds including 19F-nanoparticles and ex vivo brains from EAE mice administered with 19F-nanoparticles. The transmit/receive profile of the
19
F-CRP diminished with increasing distance from the surface. This was counterbalanced by a substantial SNR gain compared to the RT coil. Intraparenchymal inflammation in the ex vivo EAE brains was more sharply defined when using 150 μm isotropic resolution with the
19
F-CRP, and reflected the known distribution of EAE histopathology. At this spatial resolution, most 19F signals were undetectable using the RT coil. The
19
F-CRP is a valuable tool that will allow us to study neuroinflammation with greater detail in future in vivo studies.
Biomechanical properties of predator-induced body armour in the freshwater crustacean Daphnia
Authors: Kruppert Sebastian , Horstmann Martin , Weiss Linda C. , Witzel Ulrich , Schaber Clemens F. , Gorb Stanislav N. , Tollrian Ralph
Published: August 2017

The freshwater crustacean Daphnia is known for its ability to develop inducible morphological defences that thwart predators. These defences are developed only in the presence of predators and are realized as morphological shape alterations e.g. ‘neckteeth’ in D. pulex and ‘crests’ in D. longicephala. Both are discussed to hamper capture, handling or consumption by interfering with the predator’s prey capture devices. Additionally, D. pulex and some other daphniids were found to armour-up and develop structural alterations resulting in increased carapace stiffness. We used scanning transmission electron microscopy (STEM) and confocal laser scanning microscopy (CLSM) to identify predator-induced structural and shape alterations. We found species specific structural changes accompanying the known shape alterations. The cuticle becomes highly laminated (i.e. an increased number of layers) in both species during predator exposure. Using nano- and micro-indentation as well as finite element analysis (FEA) we determined both: the structure’s and shape’s contribution to the carapace’s mechanical resistance. From our results we conclude that only structural alterations are responsible for increased carapace stiffness, whereas shape alterations appear to pose handling difficulties during prey capture. Therefore, these defences act independently at different stages during predation.
A Combination of Species Identification and STR Profiling Identifies Cross-contaminated Cells from 482 Human Tumor Cell Lines
Authors: Bian Xiaocui , Yang Zhenli , Feng Hailiang , Sun Hao , Liu Yuqin
Published: August 2017

Human tumor cell lines are extremely important tools for cancer research, but a significant percentage is cross-contaminated with other cells. Short tandem repeat (STR) profiling is the prevailing standard for authenticating cell lines that originate from human tissues. Based on the analysis of 482 different human tumor cell lines used in China by STR, up to 96 cell lines were misidentified. More importantly, the study has found that STR profiling alone is insufficient to exclude inter-species cross-contamination of human cell lines. Among the 386 cell lines which had a correct STR profile, 3 of them were inter-species cross-contaminated. Careful microscopic examination may be helpful in some cases to detect changes in morphology but additional testing is needed. Additionally, species verification by PCR could easily identify the contaminants, even with a low percentage of contaminating cells. Combining STR profiling with species identification by PCR, more than 20.5% (99/482) of tumor cell lines were revealed as having been incorrectly identified, including intra-species (14.5%), inter-species (4.4%) cross-contamination and contaminating cell lines (1.7%). Therefore, quality control of cell lines is a systemic issue. Each cell line should undergo a full QA (Quality Assurance) assessment before it is used for research.
Bacteria as Bio-Template for 3D Carbon Nanotube Architectures
Authors: Ozden Sehmus , Macwan Isaac G. , Owuor Peter S. , Kosolwattana Suppanat , Autreto Pedro A. S. , Silwal Sushila , Vajtai Robert , Tiwary Chandra S. , Mohite Aditya D. , Patra Prabir K. , Ajayan Pulickel M.
Published: August 2017

It is one of the most important needs to develop renewable, scalable and multifunctional methods for the fabrication of 3D carbon architectures. Even though a lot of methods have been developed to create porous and mechanically stable 3D scaffolds, the fabrication and control over the synthesis of such architectures still remain a challenge. Here, we used Magnetospirillum magneticum (AMB-1) bacteria as a bio-template to fabricate light-weight 3D solid structure of carbon nanotubes (CNTs) with interconnected porosity. The resulting porous scaffold showed good mechanical stability and large surface area because of the excellent pore interconnection and high porosity. Steered molecular dynamics simulations were used to quantify the interactions between nanotubes and AMB-1 via the cell surface protein MSP-1 and flagellin. The 3D CNTs-AMB1 nanocomposite scaffold is further demonstrated as a potential substrate for electrodes in supercapacitor applications.
Tripolar mitosis and partitioning of the genome arrests human preimplantation development in vitro
Authors: Ottolini Christian S. , Kitchen John , Xanthopoulou Leoni , Gordon Tony , Summers Michael C. , Handyside Alan H.
Published: August 2017

Following in vitro fertilisation (IVF), only about half of normally fertilised human embryos develop beyond cleavage and morula stages to form a blastocyst in vitro. Although many human embryos are aneuploid and genomically imbalanced, often as a result of meiotic errors inherited in the oocyte, these aneuploidies persist at the blastocyst stage and the reasons for the high incidence of developmental arrest remain unknown. Here we use genome-wide SNP genotyping and meiomapping of both polar bodies to identify maternal meiotic errors and karyomapping to fingerprint the parental chromosomes in single cells from disaggregated arrested embryos and excluded cells from blastocysts. Combined with time lapse imaging of development in culture, we demonstrate that tripolar mitoses in early cleavage cause chromosome dispersal to clones of cells with identical or closely related sub-diploid chromosome profiles resulting in intercellular partitioning of the genome. We hypothesise that following zygotic genome activation (ZGA), the combination of genomic imbalance and partial genome loss disrupts the normal pattern of embryonic gene expression blocking development at the morula-blastocyst transition. Failure to coordinate the cell cycle in early cleavage and regulate centrosome duplication is therefore a major cause of human preimplantation developmental arrest in vitro.
Nano-topography Enhances Communication in Neural Cells Networks
Authors: Onesto V. , Cancedda L. , Coluccio M. L. , Nanni M. , Pesce M. , Malara N. , Cesarelli M. , Di Fabrizio E. , Amato F. , Gentile F.
Published: August 2017

Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can direct nerve cells assembly into computational efficient networks may provide new tools and criteria for tissue engineering and regenerative medicine. In this work, we used information theory approaches and functional multi calcium imaging (fMCI) techniques to examine how information flows in neural networks cultured on surfaces with controlled topography. We found that substrate roughness S
a
affects networks topology. In the low nano-meter range, S
a
 = 0–30 nm, information increases with S
a
. Moreover, we found that energy density of a network of cells correlates to the topology of that network. This reinforces the view that information, energy and surface nano-topography are tightly inter-connected and should not be neglected when studying cell-cell interaction in neural tissue repair and regeneration.
Topographical interrogation of the living cell surface reveals its role in rapid cell shape changes during phagocytosis and spreading
Authors: Jumaa Maha A. Al , Dewitt Sharon , Hallett Maurice B.
Published: August 2017

Dramatic and rapid changes in cell shape are perhaps best exemplified by phagocytes, such as neutrophils. These cells complete the processes of spreading onto surfaces, and phagocytosis within 100 s of stimulation. Although these cell shape changes are accompanied by an apparent large increase in cell surface area, the nature of the membrane “reservoir” for the additional area is unclear. One proposal is that the wrinkled cell surface topography (which forms micro-ridges on the neutrophil surface) provides the resource for neutrophils to expand their available surface area. However, it has been problematic to test this proposal in living cells because these surface structures are sub-light microscopic. In this paper, we report the development of a novel approach, a variant of FRAP (fluorescent recovery after photo-bleaching) modified to interrogate the diffusion path-lengths of membrane associated molecules. This approach provides clear evidence that the cell surface topography changes dramatically during neutrophil shape change (both locally and globally) and can be triggered by elevating cytosolic Ca2+.
Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase
Authors: Freeman Samuel L. , Martel Anne , Raven Emma L. , Roberts Gordon C. K.
Published: August 2017

NADPH-cytochrome P450 reductase is a multi-domain redox enzyme which is a key component of the P450 mono-oxygenase drug-metabolizing system. We report studies of the conformational equilibrium of this enzyme using small-angle neutron scattering, under conditions where we are able to control the redox state of the enzyme precisely. Different redox states have a profound effect on domain orientation in the enzyme and we analyse the data in terms of a two-state equilibrium between compact and extended conformations. The effects of ionic strength show that the presence of a greater proportion of the extended form leads to an enhanced ability to transfer electrons to cytochrome c. Domain motion is intrinsically linked to the functionality of the enzyme, and we can define the position of the conformational equilibrium for individual steps in the catalytic cycle.
Solar Open Flux Migration from Pole to Pole: Magnetic Field Reversal
Authors: Huang G.-H. , Lin C.-H. , Lee L. C.
Published: August 2017

Coronal holes are solar regions with low soft X-ray or low extreme ultraviolet intensities. The magnetic fields from coronal holes extend far away from the Sun, and thus they are identified as regions with open magnetic field lines. Coronal holes are concentrated in the polar regions during the sunspot minimum phase, and spread to lower latitude during the rising phase of solar activity. In this work, we identify coronal holes with outward and inward open magnetic fluxes being in the opposite poles during solar quiet period. We find that during the sunspot rising phase, the outward and inward open fluxes perform pole-to-pole trans-equatorial migrations in opposite directions. The migration of the open fluxes consists of three parts: open flux areas migrating across the equator, new open flux areas generated in the low latitude and migrating poleward, and new open flux areas locally generated in the polar region. All three components contribute to the reversal of magnetic polarity. The percentage of contribution from each component is different for different solar cycle. Our results also show that the sunspot number is positively correlated with the lower-latitude open magnetic flux area, but negatively correlated with the total open flux area.
Reference-based RADseq resolves robust relationships among closely related species of lichen-forming fungi using metagenomic DNA
Authors: Grewe Felix , Huang Jen-Pen , Leavitt Steven D. , Lumbsch H. Thorsten
Published: August 2017

Despite increasing availability of phylogenomic datasets, strategies to generate genome-scale data from organisms involved in symbiotic relationships remains challenging. Restriction site-associated DNA sequencing (RADseq) can effectively generated reduced representation genomic loci. However, when using metagenomic DNA from inseparable symbiotic organisms, RADseq loci may belong to any number of the organisms involved in these intimate associations. In this study, we explored the potential for a reference-based RADseq approach to generate data for lichen-forming fungi from metagenomic DNA extracted from intact lichens. We simulated RAD data from draft genomes of closely related lichenized fungi to test if RADseq can reconstruct robust evolutionary relationships. Subsequently, we generated empirical RADseq data from metagenomic lichen DNA, with RADseq loci mapped back to a reference genome to exclude loci from other lichen symbionts that are represented in metagenomic libraries. In all cases, phylogenetic reconstructions using RADseq loci recovered diversification histories consistent with a previous study based on more comprehensive genome sampling. Furthermore, RADseq loci were found to resolve relationships among closely related species, which were otherwise indistinguishable using a phylogenetic species recognition criterion. Our studies revealed that a modified, reference-based RADseq approach can successfully be implemented to generate symbiont-specific phylogenomic data from metagenomic reads.
Mapping White Matter Microstructure in the One Month Human Brain
Authors: Dean D. C. , Planalp E. M. , Wooten W. , Adluru N. , Kecskemeti S. R. , Frye C. , Schmidt C. K. , Schmidt N. L. , Styner M. A. , Goldsmith H. H. , Davidson R. J. , Alexander A. L.
Published: August 2017

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.
Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4
Authors: Verma Nisha , Pink Mario , Boland Stefan , Rettenmeier Albert W. , Schmitz-Spanke Simone
Published: August 2017

Benzo[a]pyrene (B[a]P), a well-known polyaromatic hydrocarbon, is known for its lung carcinogenicity, however, its role in bladder cancer development is still discussed. Comparative two-dimensional blue native SDS-PAGE analysis of protein complexes isolated from subcellular fractions of 0.5 µM B[a]P-exposed cells indicated a differential regulation of proteins involved in carbohydrate, fatty acid, and nucleotide metabolism, suggesting a possible metabolic flux redistribution. It appeared that B[a]P exposure led to a repression of enzymes (fructose-bisphosphate aldolase A, glucose-6-phosphate isomerase, lactate dehydrogenase) involved in glycolysis, and an up-regulation of proteins (glucose-6-phosphate 1-dehydrogenase, 6-phosphogluconolactonase) catalyzing the pentose phosphate pathway and one carbon metabolism (10-formyltetrahydrofolate dehydrogenase, bifunctional purine biosynthesis protein). Untargeted metabolomics further supported the proteomic data, ﻿a lower concentration of glycolytic metabolite was observed as compared to glutamine, xylulose and fatty acids. The analysis of the glutathione and NADPH/NADP+ content of the cells revealed a significant increase of these cofactors. Concomitantly, we did not observe any detectable increase in the production of ROS. With the present work, we shed light on an early phase of the metabolic stress response in which the urothelial cells are capable of counteracting oxidative stress by redirecting the metabolic flux from glycolysis to pentose phosphate pathway.
Light-sound interconversion in optomechanical Dirac materials
Authors: Wurl Christian , Fehske Holger
Published: August 2017

Analyzing the scattering and conversion process between photons and phonons coupled via radiation pressure in a circular quantum dot on a honeycomb array of optomechanical cells, we demonstrate the emergence of optomechanical Dirac physics. Specifically we prove the formation of polaritonic quasi-bound states inside the dot, and angle-dependent Klein tunneling of light and emission of sound, depending on the energy of the incident photon, the photon-phonon interaction strength, and the radius of the dot. We furthermore demonstrate that forward scattering of light or sound can almost switched off by an optically tuned Fano resonance; thereby the system may act as an optomechanical translator in a future photon-phonon based circuitry.
Gapless edge states in (C,O,H)-built molecular system with p-stacking and hydrogen bonds
Authors: Wierzbowska Małgorzata
Published: August 2017

The gapless edge states have been found in a 2D molecular system built with light atoms: C,O,H. This prediction is done on the basis of combined density functional theory (DFT) and tight-binding calculations. The system does not exhibit any effect of the spin-orbit coupling (SOC), neither intrinsic nor Rashba type. The band structure and the edge states are tuned with a strength of the p-stacking and O...H interactions. The elementary cell of this noncovalent structure, does not have the 3D inversion or rotational symmetry. Instead, the system transforms via a superposition of two reflections: with respect to the xz and xy mirror planes, both containing the non-periodic direction. This superposition is equivalent to the inversion in the 2D subspace, in which the system is periodic. The energy gap obtained with the DFT method is 0.11 eV, and largely opens (above 1 eV) with the GW and hybrid-DFT approaches. The bands inversion is partial, i.e. the Bloch states are mixed, with the ”swapping” and ”non-swapping” atomic contributions.
Robust seismicity forecasting based on Bayesian parameter estimation for epidemiological spatio-temporal aftershock clustering models
Authors: Ebrahimian Hossein , Jalayer Fatemeh
Published: August 2017

In the immediate aftermath of a strong earthquake and in the presence of an ongoing aftershock sequence, scientific advisories in terms of seismicity forecasts play quite a crucial role in emergency decision-making and risk mitigation. Epidemic Type Aftershock Sequence (ETAS) models are frequently used for forecasting the spatio-temporal evolution of seismicity in the short-term. We propose robust forecasting of seismicity based on ETAS model, by exploiting the link between Bayesian inference and Markov Chain Monte Carlo Simulation. The methodology considers the uncertainty not only in the model parameters, conditioned on the available catalogue of events occurred before the forecasting interval, but also the uncertainty in the sequence of events that are going to happen during the forecasting interval. We demonstrate the methodology by retrospective early forecasting of seismicity associated with the 2016 Amatrice seismic sequence activities in central Italy. We provide robust spatio-temporal short-term seismicity forecasts with various time intervals in the first few days elapsed after each of the three main events within the sequence, which can predict the seismicity within plus/minus two standard deviations from the mean estimate within the few hours elapsed after the main event.
Pitfalls of using confocal-microscopy based automated quantification of synaptic complexes in honeybee mushroom bodies (response to Peng and Yang 2016)
Authors: Rössler Wolfgang , Spaethe Johannes , Groh Claudia
Published: August 2017

A recent study by Peng and Yang in Scientific Reports using confocal-microscopy based automated quantification of anti-synapsin labeled microglomeruli in the mushroom bodies of honeybee brains reports potentially incorrect numbers of microglomerular densities. Whereas several previous studies using visually supervised or automated counts from confocal images and analyses of serial 3D electron-microscopy data reported consistent numbers of synaptic complexes per volume, Peng and Yang revealed extremely low numbers differing by a factor of 18 or more from those obtained in visually supervised counts, and by a factor 22–180 from numbers in two other studies using automated counts. This extreme discrepancy is especially disturbing as close comparison of raw confocal images of anti-synapsin labeled whole-mount brain preparations are highly similar across these studies. We conclude that these discrepancies may reside in potential misapplication of confocal imaging followed by erroneous use of automated image analysis software. Consequently, the reported microglomerular densities during maturation and after manipulation by insecticides require validation by application of appropriate confocal imaging methods and analyses tools that rely on skilled observers. We suggest several improvements towards more reliable or standardized automated or semi-automated synapse counts in whole mount preparations of insect brains.
Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition
Authors: Lin Yu-Wei , Raj Emmanuel Naveen , Liao Wei-Siang , Lin Johnson , Liu Kuang-Kai , Chen Ting-Hua , Cheng Hsiao-Chun , Wang Chi-Ching , Li Lily Yi , Chen Chinpiao , Chao Jui-I
Published: August 2017

The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.
Bragg Coherent Diffractive Imaging of Zinc Oxide Acoustic Phonons at Picosecond Timescales
Authors: Ulvestad A. , Cherukara M. J. , Harder R. , Cha W. , Robinson I. K. , Soog S. , Nelson S. , Zhu D. , Stephenson G. B. , Heinonen O. , Jokisaari A.
Published: August 2017

Mesoscale thermal transport is of fundamental interest and practical importance in materials such as thermoelectrics. Coherent lattice vibrations (acoustic phonons) govern thermal transport in crystalline solids and are affected by the shape, size, and defect density in nanoscale materials. The advent of hard x-ray free electron lasers (XFELs) capable of producing ultrafast x-ray pulses has significantly impacted the understanding of acoustic phonons by enabling their direct study with x-rays. However, previous studies have reported ensemble-averaged results that cannot distinguish the impact of mesoscale heterogeneity on the phonon dynamics. Here we use Bragg coherent diffractive imaging (BCDI) to resolve the 4D evolution of the acoustic phonons in a single zinc oxide rod with a spatial resolution of 50 nm and a temporal resolution of 25 picoseconds. We observe homogeneous (lattice breathing/rotation) and inhomogeneous (shear) acoustic phonon modes, which are compared to finite element simulations. We investigate the possibility of changing phonon dynamics by altering the crystal through acid etching. We find that the acid heterogeneously dissolves the crystal volume, which will significantly impact the phonon dynamics. In general, our results represent the first step towards understanding the effect of structural properties at the individual crystal level on phonon dynamics.
Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson’s disease
Authors: Saenger Victor M. , Kahan Joshua , Foltynie Tom , Friston Karl , Aziz Tipu Z. , Green Alexander L. , van Hartevelt Tim J. , Cabral Joana , Stevner Angus B. A. , Fernandes Henrique M. , Mancini Laura , Thornton John , Yousry Tarek , Limousin Patricia , Zrinzo Ludvic , Hariz Marwan , Marques Paulo , Sousa Nuno , Kringelbach Morten L. , Deco Gustavo
Published: August 2017

Deep brain stimulation (DBS) for Parkinson’s disease is a highly effective treatment in controlling otherwise debilitating symptoms. Yet the underlying brain mechanisms are currently not well understood. Whole-brain computational modeling was used to disclose the effects of DBS during resting-state functional Magnetic Resonance Imaging in ten patients with Parkinson’s disease. Specifically, we explored the local and global impact that DBS has in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts global brain dynamics of patients towards a Healthy regime. This effect was more pronounced in very specific brain areas such as the thalamus, globus pallidus and orbitofrontal regions of the right hemisphere (with the left hemisphere not analyzed given artifacts arising from the electrode lead). Global aspects of integration and synchronization were also rebalanced. Empirically, we found higher communicability and coherence brain measures during DBS-ON compared to DBS-OFF. Finally, using our model as a framework, artificial in silico DBS was applied to find potential alternative target areas for stimulation and whole-brain rebalancing. These results offer important insights into the underlying large-scale effects of DBS as well as in finding novel stimulation targets, which may offer a route to more efficacious treatments.
A novel enzyme-assisted approach for efficient extraction of Z-ligustilide from Angelica sinensis plants
Authors: Zhang Xin-Guo , Lu Ying , Wang Wen-Na , Liu Zi-Yu , Liu Jin-Wen , Chen Xiao-Qian
Published: August 2017

Endophytes coexist with plants, in part, due to cellulase that allow saccharification of plant cell walls. The cellulase enzymes found in naturally occurring endophytes may exhibit stronger activity and more specificity than commercially available cellulase for enzyme-assisted extraction of compounds from medicinal plant materials. In order to identify endophytes with high cellulase activity, we screened endophytes taken from different parts of Angelica sinensis using the Congo red staining method. We identified three strains with higher cellulase activity. Of the 3 strains identified, No.Lut1201 increased the yield of extracted Z-ligustilide 2 fold compared to commercially available cellulase (Ningxia Sunson) using a cellulase-assisted extraction method and traditional extraction methods. Scanning electron microscopy clearly demonstrated that the cellulase extracted from endophytes enhance cell wall polysaccharide degradation as well as Z-ligustilide extraction from Radix Angelica sinensis (RAS). The current study provides a new method and ideas of using cellulase of endophytes for improving the extraction of compounds from medicinal plants.
Holding of bovine blastocysts at suprazero temperatures using small molecules
Authors: Kim Daehwan , Sul Hyeonseok , Jung Yeon-Gil , Roh Sangho
Published: August 2017

Although assisted reproductive technology (ART) currently exists, the only embryo preservation technology that is available is cryopreservation. In the present study, small molecules were used to hold embryos at room temperature. The basic medium for embryo holding for a short period of time at 4 °C, 10 °C and 20 °C consisted of 1% BSA non-cryopreservation medium (BNC) instead of fetal bovine serum. To maintain survival and prevent damage during embryo incubation, three candidate small molecules were selected—CHIR99021, Y-27632 and Thiazovivin—and their concentrations were optimized. The viability and hatching rate of embryos incubated at 10 °C were greater for Y-27632-BNC and CHIR99021+Y-27632-BNC compared to BNC. However, the rate was lower for Thiazovivin-BNC compared to BNC. Although there were no surviving embryos after incubation at 20 °C, the viability and hatching rate of embryos significantly increased in Y-27632-BNC and CHIR99021+Y-27632-BNC compared to BNC. The pregnancy rate of embryos incubated at 20 °C was also greater in the CHIR99021+Y-27632-BNC group compared to that in the frozen group. The mechanism by which small molecules enhance survival of embryos during incubation was investigated, and expression of heat shock protein 70 was observed to increase. The findings of this work may be useful in improving ART in the agricultural field.
The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects
Authors: Bancone Germana , Kalnoky Michael , Chu Cindy S. , Chowwiwat Nongnud , Kahn Maria , Malleret Benoit , Wilaisrisak Pornpimon , Rénia Laurent , Domingo Gonzalo J. , Nosten Francois
Published: August 2017

Glucose-6-phosphate dehydrogenase (G6PD) activity is essential for redox equilibrium of red blood cells (RBCs) and, when compromised, the RBCs are more susceptible to haemolysis. 8-aminoquinolines (primaquine and tafenoquine) are used for the radical curative treatment of Plasmodium vivax malaria and can cause haemolysis in G6PD deficient subjects. Haemolytic risk is dependent on treatment dose and patient G6PD status but ultimately it correlates with the number of G6PD deficient RBCs. The G6PD spectrophotometric assay reliably identifies deficient subjects but is less reliable in heterozygous females, especially when other blood conditions are present. In this work we analysed samples with a range of G6PD phenotypes and haematologic conditions from 243 healthy volunteers of Asian or African-American heritage using both the spectrophotomeric assay and the G6PD flow-cytometric assay. Overall 18.5% of subjects (29.3% of Asian females) presented with anaemia, associated with decreased RBCs volume (MCV) and reticulocytosis; the flow-cytometric assay showed good correlation with the spectrophotometric assay (Pearson’s r 0.918–0.957) and was less influenced by haemoglobin concentration, number of RBCs and number of reticulocytes. This resulted in more precise quantification of the number of G6PD deficient RBCs and presumably higher predictive power of drug induced haemolytic risk.
High-altitude wind resources in the Middle East
Authors: Yip Chak Man Andrew , Gunturu Udaya Bhaskar , Stenchikov Georgiy L.
Published: August 2017

In the Middle East, near-surface wind resources are intermittent. However, high-altitude wind resources are abundant, persistent, and readily available and may provide alternative energy resources in this fossil-fuel-dependent region. Using wind field data from the Modern-Era Retrospective Analysis for Research and Applications Version 2 (MERRA-2), this study identifies areas favorable to the deployment of airborne wind energy (AWE) systems in the Middle East and computes the optimal heights at which such systems would best operate. AWE potential is estimated using realistic AWE system specifications and assumptions about deployment scenarios and is compared with the near-surface wind generation potential with respect to diurnal and seasonal variability. The results show the potential utility of AWE in areas in the Middle East where the energy demand is high. In particular, Oman and Saudi Arabia have a high level of the potential power generation with low annual variability.
Artificial gravity effect on spin-polarized exciton-polaritons
Authors: Sedov E. S. , Kavokin A. V.
Published: August 2017

The pseudospin dynamics of long-living exciton-polaritons in a wedged 2D cavity has been studied theoretically accounting for the external magnetic field effect. The cavity width variation plays the role of the artificial gravitational force acting on a massive particle: exciton-polariton. A semi-classical model of the spin-polarization dynamics of ballistically propagating exciton-polaritons has been developed. It has been shown that for the specific choice of the magnetic field magnitude and the initial polariton wave vector the polariton polarization vector tends to an attractor on the Poincaré sphere. Based on this effect, the switching of the polariton polarization in the ballistic regime has been demonstrated. The self-interference of the polariton field emitted by a point-like source has been shown to induce the formation of interference patterns.
Comprehensive transcriptome analyses reveal tomato plant responses to tobacco rattle virus-based gene silencing vectors
Authors: Zheng Yi , Ding Biao , Fei Zhangjun , Wang Ying
Published: August 2017

In plants, virus-induced gene silencing (VIGS) is a popular tool for functional genomic studies or rapidly assessing individual gene functions. However, molecular details regarding plant responses to viral vectors remain elusive, which may complicate experimental designs and data interpretation. To this end, we documented whole transcriptome changes of tomato elicited by the application of the most widely used tobacco rattle virus (TRV)-based vectors, using comprehensive genome-wide analyses. Our data illustrated multiple biological processes with functional implications, including (1) the enhanced activity of miR167 in guiding the cleavage of an auxin response factor; (2) reduced accumulation of phased secondary small interfering RNAs from two genomic loci; (3) altered expression of ~500 protein-coding transcripts; and (4) twenty long noncoding RNAs specifically responsive to TRV vectors. Importantly, we unraveled large-scale changes in mRNA alternative splicing patterns. These observations will facilitate future application of VIGS vectors for functional studies benefiting the plant research community and help deepen the understanding of plant-virus interactions.
Maximizing energy coupling to complex plasmonic devices by injecting light into eigenchannels
Authors: Jo Yonghyeon , Choi Wonjun , Seo Eunsung , Ahn Junmo , Park Q-Han , Jhon Young Min , Choi Wonshik
Published: August 2017

Surface plasmon polaritons have attracted broad attention in the optoelectronics field due to their ability to merge nanoscale electronics with high-speed optical communication. As the complexity of optoelectronic devices increases to meet various needs, this integration has been hampered by the low coupling efficiency of light to plasmonic modes. Here we present a method to maximize the coupling of far-field optical waves to plasmonic waves for arbitrarily complex devices. The method consists of experimentally identifying the eigenchannels of a given nanostructure and shaping the wavefront of incident light to a particular eigenchannel that maximizes the generation of plasmonic waves. Our proposed approach increases the coupling efficiency almost four-fold with respect to the uncontrolled input. Our study will help to facilitate the integration of electronics and photonics.
Nonsteroidal Anti-inflammatory Drug Interaction with Prostacyclin Synthase Protects from Miscarriage
Authors: Velez Edwards Digna R. , Edwards Todd L. , Bray Michael J. , Torstenson Eric , Jones Sarah , Shrubsole Martha J. , Muff Harvey J. , Hartmann Katherine E.
Published: August 2017

This study evaluates the relationship between single nucleotide polymorphisms (SNPs) in nonsteroidal anti-inflammatory drug (NSAID) metabolism and related pathways and spontaneous abortion (SAB, gestation < 20 weeks) risk. Women were enrolled in Right from the Start (2004–2010) prospective cohort. Periconceptional NSAIDs reported through the sixth week of pregnancy were obtained from study interviews. We evaluated 201 SNPs in 600 European American women. Interaction analyses between NSAID use and SNPs were conducted using logistic regression, adjusted for confounders. We also evaluated prostaglandin E2 urinary metabolite (PGE-M) in an independent population for association with SNPs using linear regression. NSAID use was reported by 63% of cases and 62% controls. The most significant interaction was at prostacyclin synthase (PGIS) rs5602 (OR = 0.34, 95% CI 0.19–0.60, p = 2.45 × 10−4) and was significant after a Bonferroni correction. NSAID users were protected from SAB (OR = 0.78, 95% CI 0.56–1.10), while non-NSAID users were at increased risk (OR = 2.11, 95% CI 1.35–3.29) in rs5602 stratified analyses. rs5602 also associated with increased PGE-M levels (Beta = 0.09, 95% CI −0.002–0.19, p = 0.033). We identified an association between a PGIS variant and SAB risk that is modified by NSAIDs use during pregnancy and directly associated with increased levels of PGE metabolites. This suggests the potential use of genetic information to guide pharmaceutical intervention to prevent adverse pregnancy outcomes.
Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage
Authors: Gai Zhibo , Chu Lei , Xu Zhenqiang , Song Xiaoming , Sun Dongfeng , Kullak-Ublick Gerd A.
Published: August 2017

Farnesoid X receptor (FXR) activation has been reported to reduce inflammation and oxidative stress. Because both inflammation and oxidative stress are critical for tissue destruction during kidney ischemia reperfusion (I/R) injury, we investigated the protective role of FXR against kidney damage induced by I/R in mice. Mice undergoing renal I/R developed the typical features of acute kidney injury (AKI): increased creatinine, albuminuria, tubular necrosis and apoptosis. Inflammatory cytokine production and oxidative stress were also markedly increased. In mice pretreated with 6-ethyl-chenodeoxycholic acid (6-ECDCA), a selective FXR agonist, I/R induced changes were prevented and renal function and structure were improved. Moreover, FXR activation also effectively prevented the subsequent progression of AKI to chronic kidney disease (CKD) by ameliorating glomerulosclerosis and interstitial fibrosis and by suppressing fibrogenic gene expression. FXR mRNA levels were inversely correlated with the progression to CKD in mice and with the degree of interstitial fibrosis in human biopsies. In further experiments administering 6-ECDCA to renal proximal tubular cells cultured under hypoxia, the renoprotective effects of FXR activation were associated with inhibition of oxidative and ER stress and with increased antioxidant activity. In conclusion, FXR agonists may have a therapeutic role in conditions associated with ischemic kidney damage.