bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass-spectrometry analysis of modifications at DNA termini induced by DNA polymerases
Authors: Smirnov Igor P. , Kolganova Natalia A. , Vasiliskov Vadim A. , Chudinov Alexander V. , Timofeev Edward N.
Published: July 2017

Non-natural nucleotide substrates are widely used in the enzymatic synthesis of modified DNA. The terminal activity of polymerases in the presence of modified nucleotides is an important, but poorly characterized, aspect of enzymatic DNA synthesis. Here, we studied different types of polymerase activity at sequence ends using extendable and non-extendable synthetic models in the presence of the Cy5-dUTP analog Y. In primer extension reactions with selected exonuclease-deficient polymerases, nucleotide Y appeared to be a preferential substrate for non-templated 3′-tailing, as determined by MALDI mass-spectrometry and gel-electrophoresis. This result was further confirmed by the 3′-tailing of a non-extendable hairpin oligonucleotide model. Additionally, DNA polymerases induce an exchange of the 3′ terminal thymidine for a non-natural nucleotide via pyrophosphorolysis in the presence of inorganic pyrophosphate. In primer extension reactions, the proofreading polymerases Vent, Pfu, and Phusion did not support the synthesis of Y-modified primer strand. Nevertheless, Pfu and Phusion polymerases were shown to initiate terminal nucleotide exchange at the template. Unlike non-proofreading polymerases, these two enzymes recruit 3′–5′ exonuclease functions to cleave the 3′ terminal thymidine in the absence of pyrophosphate.
Static Magnetic Field Stimulation Enhances Oligodendrocyte Differentiation and Secretion of Neurotrophic Factors
Authors: Prasad Ankshita , Teh Daniel B. Loong , Blasiak Agata , Chai Chou , Wu Yang , Gharibani Payam M. , Yang In Hong , Phan Thang T. , Lim Kah Leong , Yang Hyunsoo , Liu Xiaogang , All Angelo H.
Published: July 2017

The cellular-level effects of low/high frequency oscillating magnetic field on excitable cells such as neurons are well established. In contrast, the effects of a homogeneous, static magnetic field (SMF) on Central Nervous System (CNS) glial cells are less investigated. Here, we have developed an in vitro SMF stimulation set-up to investigate the genomic effects of SMF exposure on oligodendrocyte differentiation and neurotrophic factors secretion. Human oligodendrocytes precursor cells (OPCs) were stimulated with moderate intensity SMF (0.3 T) for a period of two weeks (two hours/day). The differential gene expression of cell activity marker (c-fos), early OPC (Olig1, Olig2. Sox10), and mature oligodendrocyte markers (CNP, MBP) were quantified. The enhanced myelination capacity of the SMF stimulated oligodendrocytes was validated in a dorsal root ganglion microfluidics chamber platform. Additionally, the effects of SMF on the gene expression and secretion of neurotrophic factors- BDNF and NT3 was quantified. We also report that SMF stimulation increases the intracellular calcium influx in OPCs as well as the gene expression of L-type channel subunits-CaV1.2 and CaV1.3. Our findings emphasize the ability of glial cells such as OPCs to positively respond to moderate intensity SMF stimulation by exhibiting enhanced differentiation, functionality as well as neurotrophic factor release.
From powders to bulk metallic glass composites
Authors: Krämer Lisa , Champion Yannick , Pippan Reinhard
Published: July 2017

One way to adjust the properties of materials is by changing its microstructure. This concept is not easily applicable on bulk metallic glasses (BMGs), because they do not consist of grains or different phases and so their microstructure is very homogeneous. One obvious way to integrate inhomogeneities is to produce bulk metallic glass composites (BMGCs). Here we show how to generate BMGCs via high-pressure torsion (HPT) starting from powders (amorphous Zr-MG and crystalline Cu). Using this approach, the composition can be varied and by changing the applied shear strains, the refinement of the microstructure is adjustable. This process permits to produce amorphous/crystalline composites where the scale of the phases can be varied from the micro- to the nanometer regime. Even mixing of the two phases and the generation of new metallic glasses can be achieved. The refinement of microstructure increases the hardness and a hardness higher than the initial BMG can be obtained.
Signatures of a magnetic field-induced unconventional nematic liquid in the frustrated and anisotropic spin-chain cuprate LiCuSbO4
Authors: Grafe H.-J. , Nishimoto S. , Iakovleva M. , Vavilova E. , Spillecke L. , Alfonsov A. , Sturza M.-I. , Wurmehl S. , Nojiri H. , Rosner H. , Richter J. , Rößler U. K. , Drechsler S.-L. , Kataev V. , Büchner B.
Published: July 2017

Modern theories of quantum magnetism predict exotic multipolar states in weakly interacting strongly frustrated spin-1/2 Heisenberg chains with ferromagnetic nearest neighbor (NN) inchain exchange in high magnetic fields. Experimentally these states remained elusive so far. Here we report strong indications of a magnetic field-induced nematic liquid arising above a field of ~13 T in the edge-sharing chain cuprate LiSbCuO4 ≡ LiCuSbO4. This interpretation is based on the observation of a field induced spin-gap in the measurements of the 7Li NMR spin relaxation rate T1−1 as well as a contrasting field-dependent power-law behavior of T1−1 vs. T and is further supported by static magnetization and ESR data. An underlying theoretical microscopic approach favoring a nematic scenario is based essentially on the NN XYZ exchange anisotropy within a model for frustrated spin-1/2 chains and is investigated by the DMRG technique. The employed exchange parameters are justified qualitatively by electronic structure calculations for LiCuSbO4.
Ultrafast intersystem crossings in Fe-Co Prussian blue analogues
Authors: van Veenendaal Michel
Published: July 2017

Ultrafast spincrossover is studied in Fe-Co Prussian blue analogues using a dissipative quantum-mechanical model of a cobalt ion coupled to a breathing mode. All electronic interactions are treated on an equal footing. It is theoretically demonstrated that the divalent cobalt ion reaches 90% of the $$S{\boldsymbol{=}}\frac{{\bf{3}}}{{\bf{2}}}$$
S
=

3
2

value within 20 fs after photoexciting a low-spin Co3+ ion by an iron-to-cobalt charge transfer. The doublet-to-quartet spin crossover is significantly faster than the oscillation period of the breathing mode. The system relaxes to the lowest manifold of divalent cobalt (4T1) in 150–200 fs. Strong oscillations in spin-orbit coupling and the involvement of higher-lying quartets are found.
Comparison of micro-CT imaging and histology for approximal caries detection
Authors: Boca C. , Truyen B. , Henin L. , Schulte A. G. , Stachniss V. , De Clerck N. , Cornelis J. , Bottenberg P.
Published: July 2017

Histological sectioning is a generally accepted in vitro validation method for caries detection techniques. However, it requires cumbersome sample preparation and induces irreversible sample destruction. Micro-Computer Tomography (micro-CT) allows non-destructive imaging of tooth structure. The aim of this study was to compare the performance of histological sectioning and micro-CT imaging in detecting approximal carious lesions. Unlike previous studies, evaluation is objectified by comparing visual appearance of exactly corresponding anatomical regions. Sixty extracted human teeth were scanned with a desktop micro CT system. Axial histological slices were prepared and photographed. Sample preparation, combined with dedicated image processing, ensured selection of identical anatomical regions on radiographic and histological images. Evaluation of the presence and extent of carious lesions was performed by four dentists using custom-designed software. Each section was scored independently (histo or micro CT). Scores of approximal surfaces were retained for further analysis. Spearman’s correlation coefficients (0.738 to 0.829, p < 0.0001) showed a good agreement between signs of carious lesions in the identical region obtained with both methods. Bland-Altman plots showed that 90.76% of the data points were within the limits of agreement. Micro-CT imaging was shown to provide an interesting alternative to histological sectioning as detection method for carious lesions.
Microsatellite markers for multiple Pocillopora genetic lineages offer new insights about coral populations
Authors: Nakajima Yuichi , Wepfer Patricia H. , Suzuki Shohei , Zayasu Yuna , Shinzato Chuya , Satoh Noriyuki , Mitarai Satoshi
Published: July 2017

Population genetics of the coral genus Pocillopora have been more intensively studied than those of any other reef-building taxon. However, recent investigations have revealed that the current morphological classification is inadequate to represent genetic lineages. In this study, we isolated and characterized novel microsatellite loci from morphological Pocillopora meandrina (Type 1) and Pocillopora acuta (Type 5). Furthermore, we characterized previously reported microsatellite loci. A total of 27 loci (13 novel loci) proved useful for population genetic analyses at two sites in the Ryukyu Archipelago, in the northwestern Pacific. Clonal diversity differed in each genetic lineage. Genetic structure suggested by microsatellites corresponded to clusters in a phylogenetic tree constructed from a mitochondrial open reading frame (mtORF). In addition, we found an unknown mitochondrial haplotype of this mtORF. These microsatellite loci will be useful for studies of connectivity and genetic diversity of Pocillopora populations, and will also support coral reef conservation.
Natural variations in the biofilm-associated protein BslA from the genus Bacillus
Authors: Morris Ryan J. , Schor Marieke , Gillespie Rachel M. C. , Ferreira Ana Sofia , Baldauf Lucia , Earl Chris , Ostrowski Adam , Hobley Laura , Bromley Keith M. , Sukhodub Tetyana , Arnaouteli Sofia , Stanley-Wall Nicola R. , MacPhee Cait E.
Published: July 2017

BslA is a protein secreted by Bacillus subtilis which forms a hydrophobic film that coats the biofilm surface and renders it water-repellent. We have characterised three orthologues of BslA from Bacillus amyloliquefaciens, Bacillus licheniformis and Bacillus pumilus as well as a paralogue from B. subtilis called YweA. We find that the three orthologous proteins can substitute for BslA in B. subtilis and confer a degree of protection, whereas YweA cannot. The degree to which the proteins functionally substitute for native BslA correlates with their in vitro biophysical properties. Our results demonstrate the use of naturally-evolved variants to provide a framework for teasing out the molecular basis of interfacial self-assembly.
Reconstruction of local frequencies for recovering the unwrapped phase in optical interferometry
Authors: Estrada Julio C. , Marroquin Jose L. , Medina Orlando M.
Published: July 2017

In optics, when interferograms or digital holograms are recorded and their phase is recovered, it is common to obtain a wrapped phase with some errors, noise and artifacts such as singularities due to the non linearities of the demodulation process. This paper shows how to reconstruct the frequency field of the wrapped phase by using adaptive Gabor filters. Gabor filters are Gaussian quadrature filters tuned in at a certain frequency. We adapt these Gabor filters by tuning them locally and estimating the frequency using wrapped finite differences of the estimated phase. Doing this process iteratively, the frequency estimation is refined and smoothed. The unwrapped phase is easily recovered by integrating the recovered frequency field using, for example, a simple line raster integration. We don’t have problems with phase inconsistencies or residues while integrating the phase, because these are removed. The obtained unwrapped phase is clean, consistent and practically error-free. We show estimation errors with simulated data and the performance of the proposed method using real-world recorded wavefronts.
Glucocorticoid therapy regulates podocyte motility by inhibition of Rac1
Authors: McCaffrey James C. , Webb Nicholas J. , Poolman Toryn M. , Fresquet Maryline , Moxey Cressida , Zeef Leo A. H. , Donaldson Ian J. , Ray David W. , Lennon Rachel
Published: July 2017

Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes excessively permeable leading to massive proteinuria. In childhood NS, immune system dysregulation has been implicated and increasing evidence points to the central role of podocytes in the pathogenesis. Children with NS are typically treated with an empiric course of glucocorticoid (Gc) therapy; a class of steroids that are activating ligands for the glucocorticoid receptor (GR) transcription factor. Although Gc-therapy has been the cornerstone of NS management for decades, the mechanism of action, and target cell, remain poorly understood. We tested the hypothesis that Gc acts directly on the podocyte to produce clinically useful effects without involvement of the immune system. In human podocytes, we demonstrated that the basic GR-signalling mechanism is intact and that Gc induced an increase in podocyte barrier function. Defining the GR-cistrome identified Gc regulation of motility genes. These findings were functionally validated with live-cell imaging. We demonstrated that treatment with Gc reduced the activity of the pro-migratory small GTPase regulator Rac1. Furthermore, Rac1 inhibition had a direct, protective effect on podocyte barrier function. Our studies reveal a new mechanism for Gc action directly on the podocyte, with translational relevance to designing new selective synthetic Gc molecules.
Limits of Risk Predictability in a Cascading Alternating Renewal Process Model
Authors: Lin Xin , Moussawi Alaa , Korniss Gyorgy , Bakdash Jonathan Z. , Szymanski Boleslaw K.
Published: July 2017

Most risk analysis models systematically underestimate the probability and impact of catastrophic events (e.g., economic crises, natural disasters, and terrorism) by not taking into account interconnectivity and interdependence of risks. To address this weakness, we propose the Cascading Alternating Renewal Process (CARP) to forecast interconnected global risks. However, assessments of the model’s prediction precision are limited by lack of sufficient ground truth data. Here, we establish prediction precision as a function of input data size by using alternative long ground truth data generated by simulations of the CARP model with known parameters. We illustrate the approach on a model of fires in artificial cities assembled from basic city blocks with diverse housing. The results confirm that parameter recovery variance exhibits power law decay as a function of the length of available ground truth data. Using CARP, we also demonstrate estimation using a disparate dataset that also has dependencies: real-world prediction precision for the global risk model based on the World Economic Forum Global Risk Report. We conclude that the CARP model is an efficient method for predicting catastrophic cascading events with potential applications to emerging local and global interconnected risks.
Hydrogen sulphide donors selectively potentiate a green tea polyphenol EGCG-induced apoptosis of multiple myeloma cells
Authors: Bae Jaehoon , Kumazoe Motofumi , Yamashita Shuya , Tachibana Hirofumi
Published: July 2017

Hydrogen sulphide (H2S) is a colourless gas with the odour of rotten eggs and has recently been recognized as a signal mediator in physiological activities related with the regulation of homeostasis, the vascular system and the inflammatory system. Here we show that H2S donors, including sodium hydrogen sulphide (NaHS), GYY 4137 and diallyltrisulfide (DATS), synergistically enhanced the anti-cancer effect of a green tea polyphenol (−)-epigallocatechin-3-O-gallate (EGCG) against multiple myeloma cells without affecting normal cells. NaHS significantly potentiated the anti-cancer effect of EGCG and prolonged survival in a mouse xenograft model. In this mechanism, H2S enhanced apoptotic cell death through cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase pathway induced by EGCG. Moreover, NaHS reduced the enzyme activity of cyclic nucleotide phosphodiesterase that is known as cGMP negative regulator. In conclusion, we identified H2S as a gasotransmitter that potentiates EGCG-induced cancer cell death.
CT-perfusion stroke imaging: a threshold free probabilistic approach to predict infarct volume compared to traditional ischemic thresholds
Authors: Flottmann Fabian , Broocks Gabriel , Faizy Tobias Djamsched , Ernst Marielle , Forkert Nils Daniel , Grosser Malte , Thomalla Götz , Siemonsen Susanne , Fiehler Jens , Kemmling André
Published: July 2017

The aim was to evaluate a novel method of threshold-free prediction of brain infarct from computed tomography perfusion (CTP) imaging in comparison to conventional ischemic thresholds. In a multicenter cohort of 161 patients with acute large vessel occlusion who received endovascular therapy, brain infarction was predicted by CTP using (1) optimized parameter cut-off values determined by ROC curve analysis and (2) probabilistic logistic regression threshold-free analysis. Predicted infarct volumes and prediction errors based on four perfusion parameter maps were compared against observed infarcts. In 93 patients with successful recanalization, the mean observed infarct volume was 35.7 ± 61.9 ml (the reference for core infarct not savable by reperfusion). Optimal parameter thresholds predicted mean infarct volumes between 53.2 ± 44.4 and 125.0 ± 95.4 ml whereas threshold-free analysis predicted mean volumes between 35.9 ± 28.5 and 36.1 ± 29.0 ml. In 68 patients with persistent occlusion, the mean observed infarct volume was 113.4 ± 138.3 ml (the reference to define penumbral infarct savable by reperfusion). Predicted mean infarct volumes by parameter thresholds ranged from 91.4 ± 81.5 to 163.8 ± 135.7 ml, by threshold-free analysis from 113.2 ± 89.9 to 113.5 ± 89.0 ml. Threshold-free prediction of infarct volumes had a higher precision and lower patient-specific prediction error than conventional thresholding. Penumbra to core lesion mismatch estimate may therefore benefit from threshold-free CTP analysis.
In vitro significance of SOCS-3 and SOCS-4 and potential mechanistic links to wound healing
Authors: Feng Yi , Sanders Andrew J. , Morgan Liam D. , Owen Sioned , Ruge Fiona , Harding Keith G. , Jiang Wen G.
Published: July 2017

Wound healing and the management of chronic wounds represent a significant burden on the NHS. Members of the suppressor of cytokine signalling (SOCS) family have been implicated in the regulation of a range of cellular processes. The current study aims to explore the importance of SOCS-3 and SOCS-4 in regulating cellular traits associated with wound healing. SOCS-3 over-expression and SOCS-4 knockdown mutant lines were generated and verified using q-PCR and western blotting in human keratinocytes (HaCaT) and endothelial cells (HECV). Over-expression of SOCS-3 resulted in a significantly reduced proliferative rate in HaCaT keratinocytes and also enhanced the tubule formation capacity of HECV cells. SOCS-4 knockdown significantly reduced HaCaT migration and HECV cell tubule formation. Suppression of SOCS-4 influenced the responsiveness of HaCaT and HECV cells to EGF and TGFβ and resulted in a dysregulation of phospho-protein expression in HaCaT cells. SOCS-3 and SOCS-4 appear to play regulatory roles in a number of keratinocyte and endothelial cellular traits associated with the wound healing process and may also be able to regulate the responsiveness of these cells to EGF and TGFβ. This implies a potential regulatory role in the wound healing process and, thus highlights their potential as novel therapies.
III-Nitride Digital Alloy: Electronics and Optoelectronics Properties of the InN/GaN Ultra-Short Period Superlattice Nanostructures
Authors: Sun Wei , Tan Chee-Keong , Tansu Nelson
Published: July 2017

The III-Nitride digital alloy (DA) is comprehensively studied as a short-period superlattice nanostructure consisting of ultra-thin III-Nitride epitaxial layers. By stacking the ultra-thin III-Nitride epitaxial layers periodically, these nanostructures are expected to have comparable optoelectronic properties as the conventional III-Nitride alloys. Here we carried out numerical studies on the InGaN DA showing the tunable optoelectronic properties of the III-Nitride DA. Our study shows that the energy gap of the InGaN DA can be tuned from ~0.63 eV up to ~2.4 eV, where the thicknesses and the thickness ratio of each GaN and InN ultra-thin binary layers within the DA structure are the key factors for tuning bandgap. Correspondingly, the absorption spectra of the InGaN DA yield broad wavelength tunability which is comparable to that of bulk InGaN ternary alloy. In addition, our investigation also reveals that the electron-hole wavefunction overlaps are remarkably large in the InGaN DA structure despite the existence of strain effect and build-in polarization field. Our findings point out the potential of III-Nitride DA as an artificially engineered nanostructure for optoelectronic device applications.
The LncRNA Connectivity Map: Using LncRNA Signatures to Connect Small Molecules, LncRNAs, and Diseases
Authors: Yang Haixiu , Shang Desi , Xu Yanjun , Zhang Chunlong , Feng Li , Sun Zeguo , Shi Xinrui , Zhang Yunpeng , Han Junwei , Su Fei , Li Chunquan , Li Xia
Published: July 2017

Well characterized the connections among diseases, long non-coding RNAs (lncRNAs) and drugs are important for elucidating the key roles of lncRNAs in biological mechanisms in various biological states. In this study, we constructed a database called LNCmap (LncRNA Connectivity Map), available at http://www.bio-bigdata.com/LNCmap/, to establish the correlations among diseases, physiological processes, and the action of small molecule therapeutics by attempting to describe all biological states in terms of lncRNA signatures. By reannotating the microarray data from the Connectivity Map database, the LNCmap obtained 237 lncRNA signatures of 5916 instances corresponding to 1262 small molecular drugs. We provided a user-friendly interface for the convenient browsing, retrieval and download of the database, including detailed information and the associations of drugs and corresponding affected lncRNAs. Additionally, we developed two enrichment analysis methods for users to identify candidate drugs for a particular disease by inputting the corresponding lncRNA expression profiles or an associated lncRNA list and then comparing them to the lncRNA signatures in our database. Overall, LNCmap could significantly improve our understanding of the biological roles of lncRNAs and provide a unique resource to reveal the connections among drugs, lncRNAs and diseases.
Inclusion of Population-specific Reference Panel from India to the 1000 Genomes Phase 3 Panel Improves Imputation Accuracy
Authors: Ahmad Meraj , Sinha Anubhav , Ghosh Sreya , Kumar Vikrant , Davila Sonia , Yajnik Chittaranjan S. , Chandak Giriraj R.
Published: July 2017

Imputation is a computational method based on the principle of haplotype sharing allowing enrichment of genome-wide association study datasets. It depends on the haplotype structure of the population and density of the genotype data. The 1000 Genomes Project led to the generation of imputation reference panels which have been used globally. However, recent studies have shown that population-specific panels provide better enrichment of genome-wide variants. We compared the imputation accuracy using 1000 Genomes phase 3 reference panel and a panel generated from genome-wide data on 407 individuals from Western India (WIP). The concordance of imputed variants was cross-checked with next-generation re-sequencing data on a subset of genomic regions. Further, using the genome-wide data from 1880 individuals, we demonstrate that WIP works better than the 1000 Genomes phase 3 panel and when merged with it, significantly improves the imputation accuracy throughout the minor allele frequency range. We also show that imputation using only South Asian component of the 1000 Genomes phase 3 panel works as good as the merged panel, making it computationally less intensive job. Thus, our study stresses that imputation accuracy using 1000 Genomes phase 3 panel can be further improved by including population-specific reference panels from South Asia.
Graphene transistors for interfacing with cells: towards a deeper understanding of liquid gating and sensitivity
Authors: Kireev Dmitry , Brambach Max , Seyock Silke , Maybeck Vanessa , Fu Wangyang , Wolfrum Bernhard , Offenhäusser Andreas
Published: July 2017

This work is focused on the fabrication and analysis of graphene-based, solution-gated field effect transistor arrays (GFETs) on a large scale for bioelectronic measurements. The GFETs fabricated on different substrates, with a variety of gate geometries (width/length) of the graphene channel, reveal a linear relation between the transconductance and the width/length ratio. The area normalised electrolyte-gated transconductance is in the range of 1–2 mS·V−1·□ and does not strongly depend on the substrate. Influence of the ionic strength on the transistor performance is also investigated. Double contacts are found to decrease the effective resistance and the transfer length, but do not improve the transconductance. An electrochemical annealing/cleaning effect is investigated and proposed to originate from the out-of-plane gate leakage current. The devices are used as a proof-of-concept for bioelectronic sensors, recording external potentials from both: ex vivo heart tissue and in vitro cardiomyocyte-like HL-1 cells. The recordings show distinguishable action potentials with a signal to noise ratio over 14 from ex vivo tissue and over 6 from the cardiac-like cell line in vitro. Furthermore, in vitro neuronal signals are recorded by the graphene transistors with distinguishable bursting for the first time.
ApoE Influences the Blood-Brain Barrier Through the NF-κB/MMP-9 Pathway After Traumatic Brain Injury
Authors: Teng Zhipeng , Guo Zongduo , Zhong Jianjun , Cheng Chongjie , Huang Zhijian , Wu Yue , Tang Shuang , Luo Chao , Peng Xing , Wu Haitao , Sun Xiaochuan , Jiang Li
Published: July 2017

Apolipoprotein E (ApoE), encoded by the ApoE gene (APOE), influences the outcomes of traumatic brain injury (TBI), but the mechanism remains unclear. The present study aimed to investigate the effects of different ApoEs on the outcome of TBI and to explore the possible mechanisms. Controlled cortical impact (CCI) was performed on APOEε3 (E3) and APOEε4 (E4) transgenic mice, APOE-KO (KO) mice, and wild type (WT) mice to construct an in vivo TBI model. Neurological deficits, blood brain barrier (BBB) permeability and brain edema were detected at days 1, 3, and 7 after TBI. The results revealed no significant differences among the four groups at day 1 or day 3 after injury, but more severe deficits were found in E4 and KO mice than in E3 and WT mice. Furthermore, a significant loss of tight junction proteins was observed in E4 and KO mice compared with E3 and WT mice at day 7. Additionally, more expression and activation of NF-κB and MMP-9 were found in E4 mice compared with E3 mice. Different ApoEs had distinct effects on neuro-function and BBB integrity after TBI. ApoE3, but not E4, might inhibit the NF-κB/MMP-9 pathway to alleviate BBB disruption and improve TBI outcomes.
Translational roles of the C75 2′OH in an in vitro tRNA transcript at the ribosomal A, P and E sites
Authors: Wang Jinfan , Forster Anthony C.
Published: July 2017

Aminoacyl-tRNAs containing a deoxy substitution in the penultimate nucleotide (C75 2′OH → 2′H) have been widely used in translation for incorporation of unnatural amino acids (AAs). However, this supposedly innocuous modification surprisingly increased peptidyl-tRNAAlaugc drop off in biochemical assays of successive incorporations. Here we predict the function of this tRNA 2′OH in the ribosomal A, P and E sites using recent co-crystal structures of ribosomes and tRNA substrates and test these structure-function models by systematic kinetics analyses. Unexpectedly, the C75 2′H did not affect A- to P-site translocation nor peptidyl donor activity of tRNAAlaugc. Rather, the peptidyl acceptor activity of the A-site Ala-tRNAAlaugc and the translocation of the P-site deacylated tRNAAlaugc to the E site were impeded. Delivery by EF-Tu was not significantly affected. This broadens our view of the roles of 2′OH groups in tRNAs in translation.
Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
Authors: Tong Mancy , Cheng Shi-bin , Chen Qi , DeSousa Joana , Stone Peter R. , James Joanna L. , Chamley Lawrence W. , Sharma Surendra
Published: July 2017

In preeclampsia, the serum levels of transthyretin, a carrier protein for thyroxine, are elevated. Transthyretin isolated from preeclamptic serum is also aggregated and can induce preeclampsia-like symptoms in pregnant IL10−/− mice. Using western blotting, immunofluorescence, ELISA and qRT-PCR, we investigated the production of transthyretin by preeclamptic placentae and whether transthyretin is carried into the maternal circulation via placental extracellular vesicles. Both total and aggregated transthyretin were present in higher levels in preeclamptic placentae compared to normotensive placentae (p < 0.05, n = 7), however the levels of transythretin mRNA were not significantly different (n = 8). Preeclamptic placentae secreted similar levels of total transthyretin compared to normotensive placentae (2352 ± 2949 ng/mL vs. 3250 ± 1864 ng/mL, mean ± SD, p > 0.05, n = 8), however in preeclampsia, a significant proportion is vesicle-associated (~48% vs 0%). Increased levels of aggregated transthyretin were specifically associated to preeclamptic nano-vesicles (p < 0.02, n = 8). This study showed that the placenta actively produces transthyretin and in preeclampsia, a significant amount is extruded into the maternal circulation via placental exracellular vesicles. The increased aggregation of transthyretin in preeclampsia occurs at the post-transcriptional level and while preeclamptic nano-vesicles may be removing a toxic aggregated protein from the placenta, they may also be delivering aggregated transthyretin to specific maternal organs, contributing to the pathogenesis of preeclampsia.
Antiparallel RNA G-quadruplex Formed by Human Telomere RNA Containing 8-Bromoguanosine
Authors: Xiao Chao-Da , Ishizuka Takumi , Xu Yan
Published: July 2017

In this study, by combining nuclear magnetic resonance (NMR), circular dichroism (CD), liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and gel electrophoresis, we report an unusual topological structure of the RNA G-quadruplex motif formed by human telomere RNA r(UAGGGU) containing 8-bromoguanosine. Results showed that the RNA sequence formed an antiparallel tetramolecular G-quadruplex, in which each pair of diagonal strands run in opposite directions. Furthermore, guanosines were observed both in syn- and anti-conformations. In addition, two of these G-quadruplex subunits were found to be stacking on top of each other, forming a dimeric RNA G-quadruplex. Our findings provide a new insight into the behavior of RNA G-quadruplex structures.
RhoA phosphorylation mediated by Rho/RhoA-associated kinase pathway improves the anti-freezing potentiality of murine hatched and diapaused blastocysts
Authors: Gu Meichao , Ni Hemin , Sheng Xihui , Pauciullo Alfredo , Liu Yunhai , Guo Yong
Published: July 2017

Embryonic cryopreservation has a relatively low survival rate because of cytoskeletal damage. However, molecular anti-freezing mechanisms have been largely unexplored. This study investigated the significance of RhoA, involved in embryonic development, and the Rho/RhoA-associated kinase (ROCK) signalling pathway in cryopreservation. The anti-freezing mechanism in murine dormant embryos, compared with normal blastocysts, was assessed by combining molecular, physiological and pharmacological approaches. Real-time PCR and western blotting experiments showed high RhoA expression in cryo-dormant and dormant embryos. RhoA GTPases were overexpressed on the surface of trophectoderm cells in dormant embryos. Treatment with Y-27632, a ROCK antagonist, decreased survival of both normal and dormant blastocysts, while recombinant RhoA protein remarkably increased survival, after freeze–thawing, of normal hatched blastocysts. Our findings elucidated the molecular mechanism of anti-freezing, involving RhoA phosphorylation, meditated by the Rho/ROCK signalling pathway, in hatched and diapaused murine blastocysts. In addition, evidence for a potentially protective additive suggests a new method for improving the anti-freezing potential of mammalian embryos, without protecting the zona pellucida.
Temporal trend of hepatitis B surface mutations in the post-immunization period: 9 years of surveillance (2005–2013) in eastern China
Authors: Yan Bingyu , Lv Jingjing , Feng Yi , Liu Jiaye , Ji Feng , Xu Aiqiang , Zhang Li
Published: July 2017

Limited information is available about the temporal trend in the prevalence and evolution of hepatitis B virus (HBV) S-gene mutations in the post-immunization era in China. From 2005 to 2013, 1077 hepatitis B cases under 15 years of age reported through Chinese National Notifiable Disease Reporting System (NNDRS) were successfully sequenced of S-gene in Shandong province, China. A total of 97 (9.01%) cases had amino acid (aa) substitution in the “α” determinant of HBsAg. The yearly prevalence from 2005 to 2013 maintained at a relatively stable level, and showed no significant change (P > 0.05). Multivariate logistic regression analysis demonstrated that the prevalence of “α” mutations was independently associated with the maternal HBsAg status (P < 0.05), and not with surveillance year and hepatitis B vaccination (P > 0.05). The hottest mutation position was aa126 (I126S/N and T126A, 29.63%), and aa 145 (G145R/A, 25.93%). Mutated residue 126 tended to occur less frequent, while that of residue 145 was more frequent with increasing year. Our data showed that there was no increase in the frequency of HBV “α” mutations over time during the post-immunization period. However, long-term vaccination might enhance the change of HBV mutational pattern, and G145 mutation was becoming dominant.
Using persistent photoconductivity to write a low-resistance path in SrTiO3
Authors: Poole Violet M. , Jokela Slade J. , McCluskey Matthew D.
Published: July 2017

Materials with persistent photoconductivity (PPC) experience an increase in conductivity upon exposure to light that persists after the light is turned off. Although researchers have shown that this phenomenon could be exploited for novel memory storage devices, low temperatures (below 180 K) were required. In the present work, two-point resistance measurements were performed on annealed strontium titanate (SrTiO3, or STO) single crystals at room temperature. After illumination with sub-gap light, the resistance decreased by three orders of magnitude. This markedly enhanced conductivity persisted for several days in the dark. Results from IR spectroscopy, electrical measurements, and exposure to a 405 nm laser suggest that contact resistance plays an important role. The laser was then used as an “optical pen” to write a low-resistance path between two contacts, demonstrating the feasibility of optically defined, transparent electronics.
Conjugated Linoleic Acid Supplementation Improves Maternal High Fat Diet-Induced Programming of Metabolic Dysfunction in Adult Male Rat Offspring
Authors: Segovia Stephanie A. , Vickers Mark H. , Gray Clint , Zhang Xiaoyuan D. , Reynolds Clare M.
Published: July 2017

The developmental origins of health and disease hypothesis proposes that an adverse early life environment, including in utero exposure to a maternal obesogenic environment, can lead to an increased long-term risk of obesity and related metabolic complications in offspring. We assessed whether maternal supplementation with conjugated linoleic acid (CLA) could prevent some of these adverse effects in offspring exposed to a maternal high fat diet. Sprague-Dawley dams consumed either a: control (CD), control with CLA (CLA), high fat (HF) or high fat with CLA (HFCLA) diet 10 days prior to mating and throughout pregnancy/lactation. Male offspring were weaned onto a standard chow diet. Body composition was quantified by DXA and oral glucose tolerance tests conducted on adult offspring. Gene/protein expression and histological analysis were conducted in adipose tissue. Offspring from HF dams had increased body weight, body fat deposition, impaired insulin sensitivity and adipocyte hypertrophy; all of which were rescued in HFCLA offspring. Molecular and histological analyses of the adipose tissue suggest that disturbances in adipogenesis may mediate the metabolic dysfunction observed in HF offspring. Therefore, CLA supplementation to a maternal obesogenic diet may be a promising strategy to prevent adverse programming outcomes.
Honokiol suppresses formyl peptide-induced human neutrophil activation by blocking formyl peptide receptor 1
Authors: Liu Fu-Chao , Yu Huang-Ping , Syu Yu-Ting , Fang Jia-You , Lin Chwan-Fwu , Chang Shih-Hsin , Lee Yen-Tung , Hwang Tsong-Long
Published: July 2017

Formyl peptide receptor 1 (FPR1) mediates bacterial and mitochondrial N-formyl peptides-induced neutrophil activation. Therefore, FPR1 is an important therapeutic target for drugs to treat septic or sterile inflammatory diseases. Honokiol, a major bioactive compound of Magnoliaceae plants, possesses several anti-inflammatory activities. Here, we show that honokiol exhibits an inhibitory effect on FPR1 binding in human neutrophils. Honokiol inhibited superoxide anion generation, reactive oxygen species formation, and elastase release in bacterial or mitochondrial N-formyl peptides (FPR1 agonists)-activated human neutrophils. Adhesion of FPR1-induced human neutrophils to cerebral endothelial cells was also reduced by honokiol. The receptor-binding results revealed that honokiol repressed FPR1-specific ligand N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein binding to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells. However, honokiol did not inhibit FPR2-specific ligand binding to FPR2 in human neutrophils. Furthermore, honokiol inhibited FPR1 agonist-induced calcium mobilization as well as phosphorylation of p38 MAPK, ERK, and JNK in human neutrophils. In conclusion, our data demonstrate that honokiol may have therapeutic potential for treating FPR1-mediated inflammatory diseases.
A decreasing glacier mass balance gradient from the edge of the Upper Tarim Basin to the Karakoram during 2000–2014
Authors: Lin Hui , Li Gang , Cuo Lan , Hooper Andrew , Ye Qinghua
Published: July 2017

In contrast to the glacier mass losses observed at other locations around the world, some glaciers in the High Mountains of Asia appear to have gained mass in recent decades. However, changes in digital elevation models indicate that glaciers in Karakoram and Pamir have gained mass, while recent laser altimetry data indicate mass gain centred on West Kunlun. Here, we obtain results that are essentially consistent with those from altimetry, but with two-dimensional observations and higher resolution. We produced elevation models using radar interferometry applied to bistatic data gathered between 2011 and 2014 and compared them to a model produced from bistatic data collected in 2000. The glaciers in West Kunlun, Eastern Pamir and the northern part of Karakoram experienced a clear mass gain of 0.043 ± 0.078~0.363 ± 0.065 m w.e. yr−1. The Karakoram showed a near-stable mass balance in its western part (−0.020 ± 0.064 m w.e. yr−1), while the Eastern Karakoram showed mass loss (−0.101 ± 0.058 m w.e. yr−1). Significant positive glacier mass balances are noted along the edge of the Upper Tarim Basin and indicate a decreasing gradient from northeast to southwest.
Gastric and intestinal proteases resistance of chicken acidic chitinase nominates chitin-containing organisms for alternative whole edible diets for poultry
Authors: Tabata Eri , Kashimura Akinori , Wakita Satoshi , Ohno Misa , Sakaguchi Masayoshi , Sugahara Yasusato , Kino Yoshihiro , Matoska Vaclav , Bauer Peter O. , Oyama Fumitaka
Published: July 2017

Chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc), functions as a major structural component in crustaceans, insects and fungi and is the second most abundant polysaccharide in the nature. Although these chitin-containing organisms have been suggested as novel animal feed resources, chitin has long been considered as indigestible fibers in the animal body. Recently, we reported that acidic chitinase (Chia) is a protease-resistant major glycosidase in mouse gastrointestinal tract (GIT) and that it digests chitin in the mouse stomach. However, the physiological role of Chia in other animals including poultry remains unknown. Here, we report that Chia can function as a digestive enzyme that breaks down chitin-containing organisms in chicken GIT. Chia mRNA is predominantly expressed in the glandular stomach tissue in normal chicken. We also show that chicken Chia has a robust chitinolytic activity at pH 2.0 and is highly resistant to proteolysis by pepsin and trypsin/chymotrypsin under conditions mimicking GIT. Chia degraded shells of mealworm larvae in the presence of digestive proteases and produced (GlcNAc)2. Thus, functional similarity of chicken Chia with the mouse enzyme suggests that chitin-containing organisms can be used for alternative poultry diets not only as whole edible resources but also as enhancers of their nutritional value.
2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
Authors: Chen Chunxia , Nong Zhihuan , Xie Qiuqiao , He Junhui , Cai Wene , Tang Xiuneng , Chen Xiaoyu , Huang Renbin , Gao Ying
Published: July 2017

Metastasis causes approximately 90% of breast cancer-related deaths in women. Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4-dione (DMDD) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the toxicity and efficacy of DMDD to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary carcinoma. DMDD caused no observable toxicity and significantly extended the survival of 4T1 tumor-bearing mice. DMDD effectively inhibited the growth of 4T1 cells in vitro, and suppressed the growth and metastasis of mammary tumor in vivo. The levels of inflammatory cytokines in the serum (TNF-α, IL-6, IL-12, TGF-β, and VEGF) were down regulated by DMDD. Immunohistochemical analysis demonstrated that the inhibition of tumor growth and metastasis was associated with activation of Bax, cleaved caspases-3 and -9, and down-regulation of Bcl-2, MMP-2 and -9, NF-κB and IκBα. We speculate that DMDD inhibits cytokine production in the tumor cells in mice, which leads to deactivation of NF-κB pathway, and consequently inhibits the expression of many anti-apoptosis and metastasis-promoting genes, such as Bcl-2 and MMPs. Collectively, our results demonstrate the potential of DMDD as a safe and effective antitumor agent in the treatment of late-stage breast cancer.
N-glycan mediated adhesion strengthening during pathogen-receptor binding revealed by cell-cell force spectroscopy
Authors: te Riet Joost , Joosten Ben , Reinieren-Beeren Inge , Figdor Carl G. , Cambi Alessandra
Published: July 2017

Glycan-protein lateral interactions have gained increased attention as important modulators of receptor function, by regulating surface residence time and endocytosis of membrane glycoproteins. The pathogen-recognition receptor DC-SIGN is highly expressed at the membrane of antigen-presenting dendritic cells, where it is organized in nanoclusters and binds to different viruses, bacteria and fungi. We recently demonstrated that DC-SIGN N-glycans spatially restrict receptor diffusion within the plasma membrane, favoring its internalization through clathrin-coated pits. Here, we investigated the involvement of the N-glycans of DC-SIGN expressing cells on pathogen binding strengthening when interacting with Candida fungal cells by using atomic force microscope (AFM)-assisted single cell-pathogen adhesion measurements. The use of DC-SIGN mutants lacking the N-glycans as well as blocking glycan-mediated lateral interactions strongly impaired cell stiffening during pathogen binding. Our findings demonstrate for the first time the direct involvement of the cell membrane glycans in strengthening cell-pathogen interactions. This study, therefore, puts forward a possible role for the glycocalyx as extracellular cytoskeleton contributing, possibly in connection with the intracellular actin cytoskeleton, to optimize strengthening of cell-pathogen interactions in the presence of mechanical forces.
Moiré-related in-gap states in a twisted MoS2/graphite heterojunction
Authors: Lu Chun-I , Butler Christopher J. , Huang Jing-Kai , Chu Yu-Hsun , Yang Hung-Hsiang , Wei Ching-Ming , Li Lain-Jong , Lin Minn-Tsong
Published: July 2017

This report presents a series of low-temperature (4.5 K) scanning tunneling microscopy and spectroscopy experimental results on monolayer MoS2 deposited on highly oriented pyrolytic graphite using chemical vapor deposition. To reveal the detailed connection between atomic morphology and conductivity in twisted MoS2/graphite heterojunctions, we employ high-sensitivity tunneling spectroscopy measurements by choosing a reduced tip-sample distance. We discern previously unobserved conductance peaks within the band gap range of MoS2, and by comparing the tunneling spectra from MoS2 grains of varying rotation with respect to the substrate, show that these features have small but non-negligible dependence on the moiré superstructure. Furthermore, within a single moiré supercell, atomically resolved tunneling spectroscopy measurements show that the spectra between the moiré high and low areas are also distinct. These in-gap states are shown to have an energy shift attributed to their local lattice strain, matching corresponding behavior of the conduction band edge, and we therefore infer that these features are intrinsic to the density of states, rather than experimental artifacts, and attribute them to the twisted stacking and local strain energy of the MoS2/graphite heterointerface.
Mitochondrial Dysfunction in Parkinson’s Disease
Authors: Patel Manisha , McElroy Pallavi Bhuyan
Published: July 2017

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders where oxidative stress and mitochondrial dysfunction have been implicated as etiological factors. Mitochondria are the major producers of reactive oxygen species (ROS) that can have damaging effects to cellular macromolecules leading to neurodegeneration. The most compelling evidence for the role of mitochondria in the pathogenesis of PD has been derived from toxicant-induced models of parkinsonism. Over the years, epidemiological studies have suggested a link between exposure to environmental toxins such as pesticides and the risk of developing PD. Data from human and experimental studies involving the use of chemical agents like paraquat, diquat, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and maneb have provided valuable insight into the underlying mitochondrial mechanisms contributing to PD and associated neurodegeneration. In this review, we have discussed the role of mitochondrial ROS and dysfunction in the pathogenesis of PD with a special focus on environmental agent-induced parkinsonism. We have described the various mitochondrial mechanisms by which such chemicals exert neurotoxicity, highlighting some landmark epidemiological and experimental studies that support the role of mitochondrial ROS and oxidative stress in contributing to these effects. Finally, we have discussed the significance of these studies in understanding the mechanistic underpinnings of PD-related dopaminergic neurodegeneration.