bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics
Authors: Lönn Peter , Kacsinta Apollo D. , Cui Xian-Shu , Hamil Alexander S. , Kaulich Manuel , Gogoi Khirud , Dowdy Steven F. 
Published: September 2016

AbstractBioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.
Violet LED light enhances the recruitment of a thrip predator in open fields
Authors: Ogino Takumi , Uehara Takuya , Muraji Masahiko , Yamaguchi Terumi , Ichihashi Takahisa , Suzuki Takahiro , Kainoh Yooichi , Shimoda Masami 
Published: September 2016

AbstractThe predatory bug Orius sauteri is an indigenous natural enemy of thrips and whiteflies in Asian countries. To put these bugs to practical use in pest management, methods to attract and retain the bugs in agricultural fields are needed. We previously showed that violet light (405 nm) attracts O. sauteri selectively. Many thrips and whiteflies are attracted to UV or green light. In this study, we examined the effect of violet-LED illumination on O. sauteri in pesticide-free eggplant (Solanum melongena L.) cultivation. In three cultivation trials, the density of O. sauteri on eggplant leaves was consistently higher in the illuminated plots; at least twice that of the non-illuminated plots. Simultaneously, the density of thrips declined markedly to less than half that of the non-illuminated plots. We identified three positive effects of violet light including an “immediate-effect” on predator attraction, a “persistent-effect” on predator reproduction, and a “secondary-effect” on the food web structure. Our results showed that illumination with violet light provides a powerful tool for integrated pest management. This is the first report on the use of illumination to manipulate the behavior of natural enemies.
Allergens stimulate store-operated calcium entry and cytokine production in airway epithelial cells
Authors: Jairaman Amit , Maguire Chelsea H. , Schleimer Robert P. , Prakriya Murali 
Published: September 2016

AbstractAberrant immune responses to environmental allergens including insect allergens from house dust mites and cockroaches contribute to allergic inflammatory diseases such as asthma in susceptible individuals. Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca2+is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca2+elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca2+elevations in AECs through the activation of Ca2+release-activated Ca2+(CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca2+entry then activates NFAT/calcineurin signaling to induce transcriptional production of the proinflammatory cytokines IL-6 and IL-8. These findings highlight a key role for CRAC channels as regulators of allergen induced inflammatory responses in the airway.
Symmetry Breaking by Surface Blocking: Synthesis of Bimorphic Silver Nanoparticles, Nanoscale Fishes and Apples
Authors: Cathcart Nicole , Kitaev Vladimir 
Published: September 2016

AbstractA powerful approach to augment the diversity of well-defined metal nanoparticle (MNP) morphologies, essential for MNP advanced applications, is symmetry breaking combined with seeded growth. Utilizing this approach enabled the formation of bimorphic silver nanoparticles (bi-AgNPs) consisting of two shapes linked by one regrowth point. Bi-AgNPs were formed by using an adsorbing polymer, poly(acrylic acid), PAA, to block the surface of a decahedral AgNP seed and restricting growth of new silver to a single nucleation point. First, we have realized 2-D growth of platelets attached to decahedra producing nanoscale shapes reminiscent of apples, fishes, mushrooms and kites. 1-D bimorphic growth of rods (with chloride) and 3-D bimorphic growth of cubes and bipyramids (with bromide) were achieved by using halides to induce preferential (100) stabilization over (111) of platelets. Furthermore, the universality of the formation of bimorphic nanoparticles was demonstrated by using different seeds. Bi-AgNPs exhibit strong SERS enhancement due to regular cavities at the necks. Overall, the reported approach to symmetry breaking and bimorphic nanoparticle growth offers a powerful methodology for nanoscale shape design.
Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma
Authors: Satoh Shunpei , Takatori Atsushi , Ogura Atsushi , Kohashi Kenichi , Souzaki Ryota , Kinoshita Yoshiaki , Taguchi Tomoaki , Hossain Md. Shamim , Ohira Miki , Nakamura Yohko , Nakagawara Akira 
Published: September 2016

AbstractIn neuroblastoma (NB), one of the most common paediatric solid tumours, activation of anaplastic lymphoma kinase (ALK) is often associated with poor outcomes. Although genetic studies have identified copy number alteration and nonsynonymous mutations of ALK, the regulatory mechanism of ALK signalling at protein levels is largely elusive. Neuronal leucine-rich repeat 1 (NLRR1) is a type 1 transmembrane protein that is highly expressed in unfavourable NB and potentially influences receptor tyrosine kinase signalling. Here, we showed that NLRR1 and ALK exhibited a mutually exclusive expression pattern in primary NB tissues by immunohistochemistry. Moreover, dorsal root ganglia of Nlrr1+/+ and Nlrr1−/− mice displayed the opposite expression patterns of Nlrr1 and Alk. Of interest, NLRR1 physically interacted with ALK in vitro through its extracellular region. Notably, the NLRR1 ectodomain impaired ALK phosphorylation and proliferation of ALK-mutated NB cells. A newly identified cleavage of the NLRR1 ectodomain also supported NLRR1-mediated ALK signal regulation in trans. Thus, we conclude that NLRR1 appears to be an extracellular negative regulator of ALK signalling in NB and neuronal development. Our findings may be beneficial to comprehend NB heterogeneity and to develop a novel therapy against unfavourable NB.
Oscillatory brain activity during multisensory attention reflects activation, disinhibition, and cognitive control
Authors: Friese Uwe , Daume Jonathan , Göschl Florian , König Peter , Wang Peng , Engel Andreas K. 
Published: September 2016

AbstractIn this study, we used a novel multisensory attention paradigm to investigate attention-modulated cortical oscillations over a wide range of frequencies using magnetencephalography in healthy human participants. By employing a task that required the evaluation of the congruence of audio-visual stimuli, we promoted the formation of widespread cortical networks including early sensory cortices as well as regions associated with cognitive control. We found that attention led to increased high-frequency gamma-band activity and decreased lower frequency theta-, alpha-, and beta-band activity in early sensory cortex areas. Moreover, alpha-band coherence decreased in visual cortex. Frontal cortex was found to exert attentional control through increased low-frequency phase synchronisation. Crossmodal congruence modulated beta-band coherence in mid-cingulate and superior temporal cortex. Together, these results offer an integrative view on the concurrence of oscillations at different frequencies during multisensory attention.
Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain
Authors: Labuz Dominika , Celik Melih Ö. , Zimmer Andreas , Machelska Halina 
Published: September 2016

AbstractNeuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.
A Closed Loop Brain-machine Interface for Epilepsy Control Using Dorsal Column Electrical Stimulation
Authors: Pais-Vieira Miguel , Yadav Amol P. , Moreira Derek , Guggenmos David , Santos Amílcar , Lebedev Mikhail , Nicolelis Miguel A. L. 
Published: September 2016

AbstractAlthough electrical neurostimulation has been proposed as an alternative treatment for drug-resistant cases of epilepsy, current procedures such as deep brain stimulation, vagus, and trigeminal nerve stimulation are effective only in a fraction of the patients. Here we demonstrate a closed loop brain-machine interface that delivers electrical stimulation to the dorsal column (DCS) of the spinal cord to suppress epileptic seizures. Rats were implanted with cortical recording microelectrodes and spinal cord stimulating electrodes, and then injected with pentylenetetrazole to induce seizures. Seizures were detected in real time from cortical local field potentials, after which DCS was applied. This method decreased seizure episode frequency by 44% and seizure duration by 38%. We argue that the therapeutic effect of DCS is related to modulation of cortical theta waves, and propose that this closed-loop interface has the potential to become an effective and semi-invasive treatment for refractory epilepsy and other neurological disorders.
Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis
Authors: Peng Qing-Lin , Zhang Ya-Mei , Yang Han-Bo , Shu Xiao-Ming , Lu Xin , Wang Guo-Chun 
Published: September 2016

AbstractLong non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.
Magnetic Yoking and Tunable Interactions in FePt-Based Hard/Soft Bilayers
Authors: Gilbert Dustin A. , Liao Jung-Wei , Kirby Brian J. , Winklhofer Michael , Lai Chih-Huang , Liu Kai 
Published: September 2016

AbstractMagnetic interactions in magnetic nanostructures are critical to nanomagnetic and spintronic explorations. Here we demonstrate an extremely sensitive magnetic yoking effect and tunable interactions in FePt based hard/soft bilayers mediated by the soft layer. Below the exchange length, a thin soft layer strongly exchange couples to the perpendicular moments of the hard layer; above the exchange length, just a few nanometers thicker, the soft layer moments turn in-plane and act to yoke the dipolar fields from the adjacent hard layer perpendicular domains. The evolution from exchange to dipolar-dominated interactions is experimentally captured by first-order reversal curves, the ΔM method, and polarized neutron reflectometry, and confirmed by micromagnetic simulations. These findings demonstrate an effective yoking approach to design and control magnetic interactions in wide varieties of magnetic nanostructures and devices.
Discovery of Fe7O9: a new iron oxide with a complex monoclinic structure
Authors: Sinmyo Ryosuke , Bykova Elena , Ovsyannikov Sergey V. , McCammon Catherine , Kupenko Ilya , Ismailova Leyla , Dubrovinsky Leonid 
Published: September 2016

AbstractIron oxides are fundamentally important compounds for basic and applied sciences as well as in numerous industrial applications. In this work we report the synthesis and investigation of a new binary iron oxide with the hitherto unknown stoichiometry of Fe7O9. This new oxide was synthesized at high-pressure high-temperature (HP-HT) conditions, and its black single crystals were successfully recovered at ambient conditions. By means of single crystal X-ray diffraction we determined that Fe7O9 adopts a monoclinic C2/m lattice with the most distorted crystal structure among the binary iron oxides known to date. The synthesis of Fe7O9 opens a new portal to exotic iron-rich (M,Fe)7O9 oxides with unusual stoichiometry and distorted crystal structures. Moreover, the crystal structure and phase relations of such new iron oxide groups may provide new insight into the cycling of volatiles in the Earth’s interior.
A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever
Authors: Park Ki Soo , Chung Hyun Jung , Khanam Farhana , Lee Hakho , Rashu Rasheduzzaman , Bhuiyan Md. Taufiqur , Berger Amanda , Harris Jason B. , Calderwood Stephen B. , Ryan Edward T. , Qadri Firdausi , Weissleder Ralph , Charles Richelle C. 
Published: September 2016

AbstractThere is currently no widely available optimal assay for diagnosing patients with enteric fever. Here we present a novel assay designed to detect amplified Salmonella nucleic acid (mRNA) using magneto-DNA probes and a miniaturized nuclear magnetic resonance device. We designed primers for genes specific to S. Typhi, S. Paratyphi A, and genes conserved among Salmonella enterica spp. and utilized strongly magnetized nanoparticles to enhance the detection signal. Blood samples spiked with in vitro grown S. Typhi, S. Paratyphi A, S. Typhimurium, and E. coli were used to confirm the specificity of each probe-set, and serial 10-fold dilutions were used to determine the limit of the detection of the assay, 0.01–1.0 CFU/ml. For proof of principle, we applied our assay to 0.5 mL blood samples from 5 patients with culture-confirmed enteric fever from Bangladesh in comparison to 3 healthy controls. We were able to detect amplified target cDNA in all 5 cases of enteric fever; no detectable signal was seen in the healthy controls. Our results suggest that a magneto-DNA nanoparticle system, with an assay time from blood collection of 3.5 hours, may be a promising platform for the rapid and culture-free diagnosis of enteric fever and non-typhoidal Salmonella bacteremia.
Restriction of Aerobic Metabolism by Acquired or Innate Arylsulfatase B Deficiency: A New Approach to the Warburg Effect
Authors: Bhattacharyya Sumit , Feferman Leo , Tobacman Joanne K. 
Published: September 2016

AbstractAerobic respiration is required for optimal efficiency of metabolism in mammalian cells. Under circumstances when oxygen utilization is impaired, cells survive by anerobic metabolism. The malignant cell has cultivated the use of anerobic metabolism in an aerobic environment, the Warburg effect, but the explanation for this preference is not clear. This paper presents evidence that deficiency of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase), either innate or acquired, helps to explain the Warburg phenomenon. ARSB is the enzyme that removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate and dermatan sulfate. Previous reports indicated reduced ARSB activity in malignancy and replication of the effects of hypoxia by decline in ARSB. Hypoxia reduced ARSB activity, since molecular oxygen is needed for post-translational modification of ARSB. In this report, studies were performed in human HepG2 cells and in hepatocytes from ARSB-deficient and normal C57BL/6J control mice. Decline of ARSB, in the presence of oxygen, profoundly reduced the oxygen consumption rate and increased the extracellular acidification rate, indicating preference for aerobic glycolysis. Specific study findings indicate that decline in ARSB activity enhanced aerobic glycolysis and impaired normal redox processes, consistent with a critical role of ARSB and sulfate reduction in mammalian metabolism.
Fast set-based association analysis using summary data from GWAS identifies novel gene loci for human complex traits
Authors: Bakshi Andrew , Zhu Zhihong , Vinkhuyzen Anna A. E. , Hill W. David , McRae Allan F. , Visscher Peter M. , Yang Jian 
Published: September 2016

AbstractWe propose a method (fastBAT) that performs a fast set-based association analysis for human complex traits using summary-level data from genome-wide association studies (GWAS) and linkage disequilibrium (LD) data from a reference sample with individual-level genotypes. We demonstrate using simulations and analyses of real datasets that fastBAT is more accurate and orders of magnitude faster than the prevailing methods. Using fastBAT, we analyze summary data from the latest meta-analyses of GWAS on 150,064–339,224 individuals for height, body mass index (BMI), and schizophrenia. We identify 6 novel gene loci for height, 2 for BMI, and 3 for schizophrenia at PfastBAT < 5 × 10−8. The gain of power is due to multiple small independent association signals at these loci (e.g. the THRB and FOXP1 loci for schizophrenia). The method is general and can be applied to GWAS data for all complex traits and diseases in humans and to such data in other species.
Role of coherence and delocalization in photo-induced electron transfer at organic interfaces
Authors: Abramavicius V. , Pranculis V. , Melianas A. , Inganäs O. , Gulbinas V. , Abramavicius D. 
Published: September 2016

AbstractPhoto-induced charge transfer at molecular heterojunctions has gained particular interest due to the development of organic solar cells (OSC) based on blends of electron donating and accepting materials. While charge transfer between donor and acceptor molecules can be described by Marcus theory, additional carrier delocalization and coherent propagation might play the dominant role. Here, we describe ultrafast charge separation at the interface of a conjugated polymer and an aggregate of the fullerene derivative PCBM using the stochastic Schrödinger equation (SSE) and reveal the complex time evolution of electron transfer, mediated by electronic coherence and delocalization. By fitting the model to ultrafast charge separation experiments, we estimate the extent of electron delocalization and establish the transition from coherent electron propagation to incoherent hopping. Our results indicate that even a relatively weak coupling between PCBM molecules is sufficient to facilitate electron delocalization and efficient charge separation at organic interfaces.
Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis
Authors: Chen Wen-Jen , Kuo Tzu-Yen , Hsieh Feng-Chia , Chen Pi-Yu , Wang Chang-Sheng , Shih Yu-Ling , Lai Ying-Mi , Liu Je-Ruei , Yang Yu-Liang , Shih Ming-Che 
Published: September 2016

AbstractRice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive rice diseases worldwide. Therefore, in addition to breeding disease-resistant rice cultivars, it is desirable to develop effective biocontrol agents against Xoo. Here, we report that a soil bacterium Pseudomonas taiwanensis displayed strong antagonistic activity against Xoo. Using matrix-assisted laser desorption/ionization imaging mass spectrometry, we identified an iron chelator, pyoverdine, secreted by P. taiwanensis that could inhibit the growth of Xoo. Through Tn5 mutagenesis of P. taiwanensis, we showed that mutations in genes that encode components of the type VI secretion system (T6SS) as well as biosynthesis and maturation of pyoverdine resulted in reduced toxicity against Xoo. Our results indicated that T6SS is involved in the secretion of endogenous pyoverdine. Mutations in T6SS component genes affected the secretion of mature pyoverdine from the periplasmic space into the extracellular medium after pyoverdine precursor is transferred to the periplasm by the inner membrane transporter PvdE. In addition, we also showed that other export systems, i.e., the PvdRT-OpmQ and MexAB-OprM efflux systems (for which there have been previous suggestions of involvement) and the type II secretion system (T2SS), are not involved in pyoverdine secretion.