bluuebunny/crossref_metadata_2025_split huggingface dataset:
Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
Authors: Pingel Jessica , Nielsen Mikkel Schou , Lauridsen Torsten , Rix Kristian , Bech Martin , Alkjaer Tine , Andersen Ida Torp , Nielsen Jens Bo , Feidenhansl R. 
Published: November 2017

AbstractBotulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.
Chemodrug delivery using integrin-targeted PLGA-Chitosan nanoparticle for lung cancer therapy
Authors: Babu Anish , Amreddy Narsireddy , Muralidharan Ranganayaki , Pathuri Gopal , Gali Hariprasad , Chen Allshine , Zhao Yan D. , Munshi Anupama , Ramesh Rajagopal 
Published: November 2017

AbstractIn this study, we report the efficacy of RGD (arginine-glycine-aspartic acid) peptide-modified polylactic acid-co-glycolic acid (PLGA)-Chitosan nanoparticle (CSNP) for integrin αvβ3 receptor targeted paclitaxel (PTX) delivery in lung cancer cells and its impact on normal cells. RGD peptide-modified chitosan was synthesized and then coated onto PTX-PLGA nanoparticles prepared by emulsion-solvent evaporation. PTX-PLGA-CSNP-RGD displayed favorable physicochemical properties for a targeted drug delivery system. The PTX-PLGA-CSNP-RGD system showed increased uptake via integrin receptor mediated endocytosis, triggered enhanced apoptosis, and induced G2/M cell cycle arrest and more overall cytotoxicity than its non-targeted counterpart in cancer cells. PTX-PLGA-CSNP-RGD showed less toxicity in lung fibroblasts than in cancer cells, may be attributed to low drug sensitivity, nevertheless the study invited close attention to their transient overexpression of integrin αvβ3 and cautioned against corresponding uptake of toxic drugs, if any at all. Whereas, normal human bronchial epithelial (NHBE) cells with poor integrin αvβ3 expression showed negligible toxicity to PTX-PLGA-CSNP-RGD, at equivalent drug concentrations used in cancer cells. Further, the nanoparticle demonstrated its capacity in targeted delivery of Cisplatin (CDDP), a drug having physicochemical properties different to PTX. Taken together, our study demonstrates that PLGA-CSNP-RGD is a promising nanoplatform for integrin targeted chemotherapeutic delivery to lung cancer.
Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D)
Authors: Gurney Mark E. , Cogram Patricia , Deacon Robert M , Rex Christopher , Tranfaglia Michael 
Published: November 2017

AbstractFragile-X syndrome (FXS) patients display intellectual disability and autism spectrum disorder due to silencing of the X-linked, fragile-X mental retardation-1 (FMR1) gene. Dysregulation of cAMP metabolism is a consistent finding in patients and in the mouse and fly FXS models. We therefore explored if BPN14770, a prototypic phosphodiesterase-4D negative allosteric modulator (PDE4D-NAM) in early human clinical trials, might provide therapeutic benefit in the mouse FXS model. Daily treatment of adult male fmr1 C57Bl6 knock-out mice with BPN14770 for 14 days reduced hyperarousal, improved social interaction, and improved natural behaviors such as nesting and marble burying as well as dendritic spine morphology. There was no decrement in behavioral scores in control C57Bl6 treated with BPN14770. The behavioral benefit of BPN14770 persisted two weeks after washout of the drug. Thus, BPN14770 may be useful for the treatment of fragile-X syndrome and other disorders with decreased cAMP signaling.
Optical mapping of the dominant frequency of brain signal oscillations in motor systems
Authors: Lu Feng-Mei , Wang Yi-Feng , Zhang Juan , Chen Hua-Fu , Yuan Zhen 
Published: November 2017

AbstractRecent neuroimaging studies revealed that the dominant frequency of neural oscillations is brain-region-specific and can vary with frequency-specific reorganization of brain networks during cognition. In this study, we examined the dominant frequency in low-frequency neural oscillations represented by oxygenated hemoglobin measurements after the hemodynamic response function (HRF) deconvolution. Twenty-nine healthy college subjects were recruited to perform a serial finger tapping task at the frequency of 0.2 Hz. Functional near-infrared spectroscopy (fNIRS) was applied to record the hemodynamic signals over the primary motor cortex, supplementary motor area (SMA), premotor cortex, and prefrontal area. We then explored the low frequency steady-state brain response (lfSSBR), which was evoked in the motor systems at the fundamental frequency (0.2 Hz) and its harmonics (0.4, 0.6, and 0.8 Hz). In particular, after HRF deconvolution, the lfSSBR at the frequency of 0.4 Hz in the SMA was identified as the dominant frequency. Interestingly, the domain frequency exhibited the correlation with behavior data such as reaction time, indicating that the physiological implication of lfSSBR is related to the brain anatomy, stimulus frequency and cognition. More importantly, the HRF deconvolution showed its capability for recovering signals probably reflecting neural-level events and revealing the physiological meaning of lfSSBR.
Urinary sulphatoxymelatonin as a biomarker of serotonin status in biogenic amine-deficient patients
Authors: Batllori Marta , Molero-Luis Marta , Arrabal Luisa , Heras Javier de las , Fernandez-Ramos Joaquín-Alejandro , Gutiérrez-Solana Luis González , Ibáñez-Micó Salvador , Domingo Rosario , Campistol Jaume , Ormazabal Aida , Sedel Frederic , Opladen Thomas , Zouvelou Basiliki , Pons Roser , Garcia-Cazorla Angels , Lopez-Laso Eduardo , Artuch Rafael 
Published: November 2017

AbstractMelatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency. Further 11 patients were studied after receiving serotoninergic treatment (serotonin precursors, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors): 5 with aromatic L-amino acid decarboxylase deficiency; 1 with sepiapterin reductase deficiency; 3 with dihydropteridine reductase deficiency; and 2 with 6-pyruvoyltetrahydropterin synthase deficiency. Among the patients without therapy, 6 presented low urinary sulphatoxymelatonin values, while most of the patients with guanosine triphosphate cyclohydrolase-I deficiency showed normal values. 5 of 11 patients under treatment presented low urine sulphatoxymelatonin values. Thus, decreased excretion of sulphatoxymelatonin is frequently observed in cases with severe genetic disorders affecting serotonin biosynthesis. In conclusion, sulphatoxymelatonin can be a good biomarker to estimate serotonin status in the brain, especially for treatment monitoring purposes.
ToxId: an efficient algorithm to solve occlusions when tracking multiple animals
Authors: Rodriguez Alvaro , Zhang Hanqing , Klaminder Jonatan , Brodin Tomas , Andersson Magnus 
Published: November 2017

AbstractVideo analysis of animal behaviour is widely used in fields such as ecology, ecotoxicology, and evolutionary research. However, when tracking multiple animals, occlusion and crossing are problematic, especially when the identity of each individual needs to be preserved. We present a new algorithm, ToxId, which preserves the identity of multiple animals by linking trajectory segments using their intensity histogram and Hu-moments. We verify the performance and accuracy of our algorithm using video sequences with different animals and experimental conditions. The results show that our algorithm achieves state-of-the-art accuracy using an efficient approach without the need of learning processes, complex feature maps or knowledge of the animal shape. ToxId is also computationally efficient, has low memory requirements, and operates without accessing future or past frames.
Development of multivariable models to predict change in Body Mass Index within a clinical trial population of psychotic individuals
Authors: Harrison Rebecca N. S. , Gaughran Fiona , Murray Robin M. , Lee Sang Hyuck , Cano Jose Paya , Dempster David , Curtis Charles J. , Dima Danai , Patel Hamel , de Jong Simone , Breen Gerome 
Published: November 2017

AbstractMany antipsychotics promote weight gain, which can lead to non-compliance and relapse of psychosis. By developing models that accurately identify individuals at greater risk of weight gain, clinicians can make informed treatment decisions and target intervention measures. We examined clinical, genetic and expression data for 284 individuals with psychosis derived from a previously published randomised controlled trial (IMPACT). These data were used to develop regression and classification models predicting change in Body Mass Index (BMI) over one year. Clinical predictors included demographics, anthropometrics, cardiac and blood measures, diet and exercise, physical and mental health, medication and BMI outcome measures. We included genetic polygenic risk scores (PRS) for schizophrenia, bipolar disorder, BMI, waist-hip-ratio, insulin resistance and height, as well as gene co-expression modules generated by Weighted Gene Co-expression Network Analysis (WGCNA). The best performing predictive models for BMI and BMI gain after one year used clinical data only, which suggests expression and genetic data do not improve prediction in this cohort.
Comparison of Transcriptomic Platforms for Analysis of Whole Blood from Ebola-Infected Cynomolgus Macaques
Authors: Speranza Emily , Altamura Louis A. , Kulcsar Kirsten , Bixler Sandra L. , Rossi Cynthia A. , Schoepp Randal J. , Nagle Elyse , Aguilar William , Douglas Christina E. , Delp Korey L. , Minogue Timothy D. , Palacios Gustavo , Goff Arthur J. , Connor John H. 
Published: November 2017

AbstractEbola virus disease (EVD) is a serious illness with mortality rates of 20–90% in various outbreaks. EVD is characterized by robust virus replication and strong host inflammatory response. Analyzing host immune responses has increasingly involved multimodal approaches including transcriptomics to profile gene expression. We studied cynomolgus macaques exposed to Ebola virus Makona via different routes with the intent of comparing RNA-Seq to a NanoString nCounter codeset targeting 769 non-human primate (NHP) genes. RNA-Seq analysis of serial blood samples showed different routes led to the same overall transcriptional response seen in previously reported EBOV-exposed NHP studies. Both platforms displayed a strong correlation in gene expression patterns, including a strong induction of innate immune response genes at early times post-exposure, and neutrophil-associated genes at later time points. A 41-gene classifier was tested in both platforms for ability to cluster samples by infection status. Both NanoString and RNA-Seq could be used to predict relative abundances of circulating immune cell populations that matched traditional hematology. This demonstrates the complementarity of RNA-Seq and NanoString. Moreover, the development of an NHP-specific NanoString codeset should augment studies of filoviruses and other high containment infectious diseases without the infrastructure requirements of RNA-Seq technology.
Broadband suppression of backscattering at optical frequencies using low permittivity dielectric spheres
Authors: Ismail Abdelrahman M. , Rockstuhl C. , Fernandez-Corbaton I. 
Published: November 2017

AbstractThe exact suppression of backscattering from rotationally symmetric objects requires dual symmetric materials where εr = μr. This prevents their design at many frequency bands, including the optical one, because magnetic materials are not available. Electromagnetically small non-magnetic spheres of large permittivity offer an alternative. They can be tailored to exhibit balanced electric and magnetic dipole polarizabilities a1 = b1, which result in approximate zero backscattering. In this case, the effect is inherently narrowband. Here, we put forward a different alternative that allows broadband functionality: Wavelength-sized spheres made from low permittivity materials. The effect occurs in a parameter regime where approximate duality is met for all multipolar order a
n
≈ b
n
, in a weakly wavelength dependence fashion. In addition, and despite of the low permittivity, the overall scattering response of these spheres is still significant. Scattering patterns are shown to be highly directive across an octave spanning band. The effect is analytically and numerically shown using the Mie coefficients.
No evidence of widespread decline of snow cover on the Tibetan Plateau over 2000–2015
Authors: Wang Xiaoyue , Wu Chaoyang , Wang Huanjiong , Gonsamo Alemu , Liu Zhengjia 
Published: November 2017

AbstractUnderstanding the changes in snow cover is essential for biological and hydrological processes in the Tibetan Plateau (TP) and its surrounding areas. However, the changes in snow cover phenology over the TP have not been well documented. Using Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow products and the Interactive Multi-sensor Snow and Ice Mapping System (IMS) data, we reported daily cloud-free snow cover product over the Tibetan Plateau (TP) for 2000–2015. Snow cover start (SCS), melt (SCM) and duration (SCD) dates were calculated for each hydrological year, and their spatial and temporal variations were analyzed with elevation variations. Our results show no widespread decline in snow cover over the past fifteen years and the trends of snow cover phenology over the TP has high spatial heterogeneity. Later SCS, earlier SCM, and thus decreased SCD mainly occurred in the areas with elevation below 3500 m a.s.l., while regions in central and southwestern edges of the TP showed advanced SCS, delayed SCM and consequently longer SCD. The roles of temperature and precipitation on snow cover penology varied in different elevation zones, and the impact of both temperature and precipitation strengthened as elevation increases.
Inactivation mechanism of N61S mutant of human FMO3 towards trimethylamine
Authors: Gao Chongliang , Catucci Gianluca , Castrignanò Silvia , Gilardi Gianfranco , Sadeghi Sheila J. 
Published: November 2017

AbstractHuman flavin-containing monooxygenase 3 (hFMO3) catalyses the oxygenation of a wide variety of compounds including drugs as well as dietary compounds. It is the major hepatic enzyme involved in the production of the N-oxide of trimethylamine (TMAO) and clinical studies have uncovered a striking correlation between plasma TMAO concentration and cardiovascular disease. Certain mutations within the hFMO3 gene cause defective trimethylamine (TMA) N-oxygenation leading to trimethylaminuria (TMAU) also known as fish-odour syndrome. In this paper, the inactivation mechanism of a TMAU-causing polymorphic variant, N61S, is investigated. Transient kinetic experiments show that this variant has a > 170-fold lower NADPH binding affinity than the wild type. Thermodynamic and spectroscopic experiments reveal that the poor NADP+ binding affinity accelerates the C4a-hydroperoxyFAD intermediate decay, responsible for an unfavourable oxygen transfer to the substrate. Steady-state kinetic experiments show significantly decreased N61S catalytic activity towards other substrates; methimazole, benzydamine and tamoxifen. The in vitro data are corroborated by in silico data where compared to the wild type enzyme, a hydrogen bond required for the stabilisation of the flavin intermediate is lacking. Taken together, the data presented reveal the molecular basis for the loss of function observed in N61S mutant.
Broadband enhancement of photoluminance from colloidal metal halide perovskite nanocrystals on plasmonic nanostructured surfaces
Authors: Zhang Si , Liang Yuzhang , Jing Qiang , Lu Zhenda , Lu Yanqing , Xu Ting 
Published: November 2017

AbstractMetal halide perovskite nanocrystals (NCs) as a new kind of promising optoelectronic material have attracted wide attention due to their high photoluminescence (PL) quantum yield, narrow emission linewidth and wideband color tunability. Since the PL intensity always has a direct influence on the performance of optoelectronic devices, it is of vital importance to improve the perovskite NCs’ fluorescence emission efficiency. Here, we synthesize three inorganic perovskite NCs and experimentally demonstrate a broadband fluorescence enhancement of perovskite NCs by exploiting plasmonic nanostructured surface consisting of nanogrooves array. The strong near-field optical localization associated with surface plasmon polariton-coupled emission effect generated by the nanogrooves array can significantly boost the absorption of perovskite NCs and tailor the fluorescence emissions. As a result, the PL intensities of perovskite NCs are broadband enhanced with a maximum factor higher than 8-fold achieved in experimental demonstration. Moreover, the high efficiency PL of perovskite NCs embedded in the polymer matrix layer on the top of plasmonic nanostructured surface can be maintained for more than three weeks. These results imply that plasmonic nanostructured surface is a good candidate to stably broadband enhance the PL intensity of perovskite NCs and further promote their potentials in the application of visible-light-emitting devices.
Thalidomide Inhibits TGF-β1-induced Epithelial to Mesenchymal Transition in Alveolar Epithelial Cells via Smad-Dependent and Smad-Independent Signaling Pathways
Authors: Zhou Xian-Long , Xu Peng , Chen Hai-Hua , Zhao Yan , Shen Jun , Jiang Cheng , Jiang Shan , Ni Shao-Zhou , Xu Bing , Li Lei 
Published: November 2017

AbstractRecent evidence indicates that the epithelial to mesenchymal transition (EMT) in primary alveolar cells (AECs) plays an important role in idiopathic pulmonary fibrosis (IPF). In vivo models have suggested that thalidomide (THL) has anti-fibrotic effects against pulmonary fibrosis, but the underlying mechanism of this effect is not clear. This study investigated whether THL regulates alveolar EMT and the possible mechanisms underlying this process. CCL-149 cells were treated with TGF-β1 in the presence of THL at the indicated concentrations. EMT was assessed by changes in cell morphology and in phenotypic markers. Signaling pathways involved in EMT were characterized by western blot analysis. THL inhibited the TGF-β1 induction of α-SMA, vimentin, MMP-2/-9 and collagen type IV expression and restored the morphological changes in primary alveolar epithelial cells caused by TGF-β1. TGF-β1 induction of α-SMA expression was partially dependent on the activation of p38, JNK, ERK, Akt, Smad 2 and Smad3. Moreover, THL inhibited TGF-β1-induced phosphorylation of p38, JNK, ERK, Akt, GSK3β, Smad 2 and Smad3 without altering the total expression levels of those proteins. These findings indicate that TGF-β1-induced EMT in alveolar epithelial cells is inhibited by THL via both Smad-dependent and non-Smad-dependent signaling pathways and suggests therapeutic approaches for targeting this process in pulmonary fibrosis.
Working memory, attention, and salience in active inference
Authors: Parr Thomas , Friston Karl J 
Published: November 2017

AbstractThe psychological concepts of working memory and attention are widely used in the cognitive and neuroscientific literatures. Perhaps because of the interdisciplinary appeal of these concepts, the same terms are often used to mean very different things. Drawing on recent advances in theoretical neurobiology, this paper tries to highlight the correspondence between these established psychological constructs and the formal processes implicit in mathematical descriptions of brain function. Here, we consider attention and salience from the perspective offered by active inference. Using variational principles and simulations, we use active inference to demonstrate how attention and salience can be disambiguated in terms of message passing between populations of neurons in cortical and subcortical structures. In brief, we suggest that salience is something that is afforded to actions that realise epistemic affordance, while attention per se is afforded to precise sensory evidence – or beliefs about the causes of sensations.
Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome
Authors: Chandran Jayanth S. , Sharp Paul S. , Karyka Evangelia , Aves-Cruzeiro João Miguel da Conceição , Coldicott Ian , Castelli Lydia , Hautbergue Guillaume , Collins Mark O. , Azzouz Mimoun 
Published: November 2017

AbstractAdeno-associated viruses (AAVs) are attractive gene therapy vectors due to their low toxicity, high stability, and rare integration into the host genome. Expressing ligands on the viral capsid can re-target AAVs to new cell types, but limited sites have been identified on the capsid that tolerate a peptide insertion. Here, we incorporated a site-specific tetracysteine sequence into the AAV serotype 9 (AAV9) capsid, to permit labelling of viral particles with either a fluorescent dye or biotin. We demonstrate that fluorescently labelled particles are detectable in vitro, and explore the utility of the method in vivo in mice with time-lapse imaging. We exploit the biotinylated viral particles to generate two distinct AAV interactomes, and identify several functional classes of proteins that are highly represented: actin/cytoskeletal protein binding, RNA binding, RNA splicing/processing, chromatin modifying, intracellular trafficking and RNA transport proteins. To examine the biological relevance of the capsid interactome, we modulated the expression of two proteins from the interactomes prior to AAV transduction. Blocking integrin αVβ6 receptor function reduced AAV9 transduction, while reducing histone deacetylase 4 (HDAC4) expression enhanced AAV transduction. Our method demonstrates a strategy for inserting motifs into the AAV capsid without compromising viral titer or infectivity.