bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caregiver burden and caregiver appraisal of psychiatric symptoms are not modulated by subthalamic deep brain stimulation for Parkinson’s disease
Authors: Mosley Philip E. , Breakspear Michael , Coyne Terry , Silburn Peter , Smith David 
Published: April 2018

AbstractSubthalamic deep brain stimulation is an advanced therapy that typically improves quality of life for persons with Parkinson’s disease (PD). However, the effect on caregiver burden is unclear. We recruited 64 persons with PD and their caregivers from a movement disorders clinic during the assessment of eligibility for subthalamic DBS. We used clinician-, patient- and caregiver-rated instruments to follow the patient–caregiver dyad from pre- to postoperative status, sampling repeatedly in the postoperative period to ascertain fluctuations in phenotypic variables. We employed multivariate models to identify key drivers of burden. We clustered caregiver-rated variables into ‘high’ and ‘low’ symptom groups and examined whether postoperative cluster assignment could be predicted from baseline values. Psychiatric symptoms in the postoperative period made a substantial contribution to longitudinal caregiver burden. The development of stimulation-dependent mood changes was also associated with increased burden. However, caregiver burden and caregiver-rated psychiatric symptom clusters were temporally stable and thus predicted only by their baseline values. We confirmed this finding using frequentist and Bayesian statistics, concluding that in our sample, subthalamic DBS for PD did not significantly influence caregiver burden or caregiver-rated psychiatric symptoms. Specifically, patient–caregiver dyads with high burden and high levels of psychiatric symptoms at baseline were likely to maintain this profile during follow-up. These findings support the importance of assessing caregiver burden prior to functional neurosurgery. Furthermore, they suggest that interventions addressing caregiver burden in this population should target those with greater symptomatology at baseline and may usefully prioritise psychiatric symptoms reported by the caregiver.
Translation of remote control regenerative technologies for bone repair
Authors: Markides Hareklea , McLaren Jane S. , Telling Neil D. , Alom Noura , Al-Mutheffer E’atelaf A. , Oreffo Richard O. C. , Zannettino Andrew , Scammell Brigitte E. , White Lisa J. , El Haj Alicia J. 
Published: April 2018

AbstractThe role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48 h post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents.
Electrical and optical properties of epitaxial binary and ternary GeTe-Sb2Te3 alloys
Authors: Boschker Jos E. , Lü Xiang , Bragaglia Valeria , Wang Ruining , Grahn Holger T. , Calarco Raffaella 
Published: April 2018

AbstractPhase change materials such as pseudobinary GeTe-Sb2Te3 (GST) alloys are an essential part of existing and emerging technologies. Here, we investigate the electrical and optical properties of epitaxial phase change materials: α-GeTe, Ge2Sb2Te5 (GST225), and Sb2Te3. Temperature-dependent Hall measurements reveal a reduction of the hole concentration with increasing temperature in Sb2Te3 that is attributed to lattice expansion, resulting in a non-linear increase of the resistivity that is also observed in GST225. Fourier transform infrared spectroscopy at room temperature demonstrates the presence of electronic states within the energy gap for α-GeTe and GST225. We conclude that these electronic states are due to vacancy clusters inside these two materials. The obtained results shed new light on the fundamental properties of phase change materials such as the high dielectric constant and persistent photoconductivity and have the potential to be included in device simulations.
Intrinsically-disordered N-termini in human parechovirus 1 capsid proteins bind encapsidated RNA
Authors: Shakeel Shabih , Evans James D. , Hazelbaker Mark , Kao C. Cheng , Vaughan Robert C. , Butcher Sarah J. 
Published: April 2018

AbstractHuman parechoviruses (HPeV) are picornaviruses with a highly-ordered RNA genome contained within icosahedrally-symmetric capsids. Ordered RNA structures have recently been shown to interact with capsid proteins VP1 and VP3 and facilitate virus assembly in HPeV1. Using an assay that combines reversible cross-linking, RNA affinity purification and peptide mass fingerprinting (RCAP), we mapped the RNA-interacting regions of the capsid proteins from the whole HPeV1 virion in solution. The intrinsically-disordered N-termini of capsid proteins VP1 and VP3, and unexpectedly, VP0, were identified to interact with RNA. Comparing these results to those obtained using recombinantly-expressed VP0 and VP1 confirmed the virion binding regions, and revealed unique RNA binding regions in the isolated VP0 not previously observed in the crystal structure of HPeV1. We used RNA fluorescence anisotropy to confirm the RNA-binding competency of each of the capsid proteins’ N-termini. These findings suggests that dynamic interactions between the viral RNA and the capsid proteins modulate virus assembly, and suggest a novel role for VP0.
On the contributing role of the transmembrane domain for subunit-specific sensitivity of integrin activation
Authors: Pagani Giulia , Gohlke Holger 
Published: April 2018

AbstractIntegrins are α/β heterodimeric transmembrane adhesion receptors. Evidence exists that their transmembrane domain (TMD) separates upon activation. Subunit-specific differences in activation sensitivity of integrins were reported. However, whether sequence variations in the TMD lead to differential TMD association has remained elusive. Here, we show by molecular dynamics simulations and association free energy calculations on TMDs of integrin αIIbβ3, αvβ3, and α5β1 that αIIbβ3 TMD is most stably associated; this difference is related to interaction differences across the TMDs. The order of TMD association stability is paralleled by the basal activity of these integrins, which suggests that TMD differences can have a decisive effect on integrin conformational free energies. We also identified a specific order of clasp disintegration upon TMD dissociation, which suggests that the closed state of integrins may comprise several microstates. Our results provide unprecedented insights into a possibly contributing role of TMD towards subunit-specific sensitivity of integrin activation.
An estradiol-independent BDNF-NPY cascade is involved in the antidepressant effect of mechanical acupuncture instruments in ovariectomized rats
Authors: Seo Su Yeon , Moon Ji-Young , Kang Suk-Yun , Kwon O. Sang , Kwon Sunoh , Bang Se kyun , Kim Soo Phil , Choi Kwang-Ho , Ryu Yeonhee 
Published: April 2018

AbstractMenopause-related depression devastates women’s quality of life after middle age. Previous research has shown that estrogen hormone therapy has serious adverse effects; thus, complementary and integrative therapies have been considered clinically. The present study investigates whether stimulation of an acupoint using a mechanical acupuncture instrument (MAI) can mitigate depression-like behavior caused by estrogen deficiency in ovariectomized (OVX) rats. The animals were divided into Sham OVX, OVX, OVX + Sameumgyo (SP6) and OVX + NonAcu (non-acupuncture point) groups. MAI stimulation significantly increased the total distance traveled in the open-field test and the number of open-arm entries in the elevated plus maze and decreased the duration of immobility in the forced swim test. In addition to this decrease in depression-like behavior, brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) release increased in the hippocampus in response to MAI treatment, but estradiol levels did not recover. Furthermore, microinjection of the BDNF receptor antagonist ANA-12 (0.1 pmol/1 μl) into the hippocampus before MAI stimulation significantly suppressed the recovery of NPY levels. Taken together, these findings indicate that MAI stimulation at SP6 facilitates an estradiol-independent BDNF-NPY cascade, which may contribute to its antidepressant effects in OVX rats, an animal model of menopausal disorders.
Bayesian-Driven First-Principles Calculations for Accelerating Exploration of Fast Ion Conductors for Rechargeable Battery Application
Authors: Jalem Randy , Kanamori Kenta , Takeuchi Ichiro , Nakayama Masanobu , Yamasaki Hisatsugu , Saito Toshiya 
Published: April 2018

AbstractSafe and robust batteries are urgently requested today for power sources of electric vehicles. Thus, a growing interest has been noted for fabricating those with solid electrolytes. Materials search by density functional theory (DFT) methods offers great promise for finding new solid electrolytes but the evaluation is known to be computationally expensive, particularly on ion migration property. In this work, we proposed a Bayesian-optimization-driven DFT-based approach to efficiently screen for compounds with low ion migration energies ($${{\boldsymbol{E}}}_{{\boldsymbol{b}}}{\boldsymbol{)}}$$

E

b

)
. We demonstrated this on 318 tavorite-type Li- and Na-containing compounds. We found that the scheme only requires ~30% of the total DFT-$${{\boldsymbol{E}}}_{{\boldsymbol{b}}}$$

E

b

evaluations on the average to recover the optimal compound ~90% of the time. Its recovery performance for desired compounds in the tavorite search space is ~2× more than random search (i.e., for $${{\boldsymbol{E}}}_{{\boldsymbol{b}}}$$

E

b

< 0.3 eV). Our approach offers a promising way for addressing computational bottlenecks in large-scale material screening for fast ionic conductors.
Stimulation of TLR3 triggers release of lysosomal ATP in astrocytes and epithelial cells that requires TRPML1 channels
Authors: Beckel Jonathan M. , Gómez Néstor Más , Lu Wennan , Campagno Keith E. , Nabet Bardia , Albalawi Farraj , Lim Jason C. , Boesze-Battaglia Kathleen , Mitchell Claire H. 
Published: April 2018

AbstractCross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was accompanied by lysosomal acid phosphatase and beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine-2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with LysoTracker. Unmodified membrane-impermeant 21-nt and “non-targeting” scrambled 21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and in TRPML1−/− cells, while TRPML activation with ML-SA1 was sufficient to release both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca2+ was abolished by removing extracellular ATP with apyrase, suggesting ATP release by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal alkalization and release of lysosomal ATP through activation of TRPML1; this links innate immunity to purinergic signaling via lysosomal physiology, and suggests even scrambled siRNA can influence these pathways.
Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells
Authors: Dvoriantchikova Galina , Pronin Alexey , Kurtenbach Sarah , Toychiev Abduqodir , Chou Tsung-Han , Yee Christopher W. , Prindeville Breanne , Tayou Junior , Porciatti Vittorio , Sagdullaev Botir T. , Slepak Vladlen Z. , Shestopalov Valery I. 
Published: April 2018

AbstractPannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells. The analysis of pattern electroretinogram (PERG) recordings indicated that Panx1 contributes to the electrical output of the retina. Consistently, PERG amplitudes were significantly impaired in the eyes with targeted ablation of the Panx1 gene in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1 activity permeated cell membranes and facilitated the selective loss of RGCs or stably transfected Neuro2A cells. Our results show that high expression of the Panx1 channel in RGCs is essential for visual function in the inner retina but makes these cells highly sensitive to mechanical and ischemic stresses. These findings are relevant to the pathophysiology of retinal disorders induced by increased intraocular pressure, such as glaucoma.
Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease
Authors: Frejo Lidia , Gallego-Martinez Alvaro , Requena Teresa , Martin-Sanz Eduardo , Amor-Dorado Juan Carlos , Soto-Varela Andres , Santos-Perez Sofia , Espinosa-Sanchez Juan Manuel , Batuecas-Caletrio Angel , Aran Ismael , Fraile Jesus , Rossi-Izquierdo Marcos , Lopez-Escamez Jose Antonio 
Published: April 2018

AbstractEpidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere’s disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.
Structure and co-occurrence patterns in microbial communities under acute environmental stress reveal ecological factors fostering resilience
Authors: Mandakovic Dinka , Rojas Claudia , Maldonado Jonathan , Latorre Mauricio , Travisany Dante , Delage Erwan , Bihouée Audrey , Jean Géraldine , Díaz Francisca P. , Fernández-Gómez Beatriz , Cabrera Pablo , Gaete Alexis , Latorre Claudio , Gutiérrez Rodrigo A. , Maass Alejandro , Cambiazo Verónica , Navarrete Sergio A. , Eveillard Damien , González Mauricio 
Published: April 2018

AbstractUnderstanding the factors that modulate bacterial community assembly in natural soils is a longstanding challenge in microbial community ecology. In this work, we compared two microbial co-occurrence networks representing bacterial soil communities from two different sections of a pH, temperature and humidity gradient occurring along a western slope of the Andes in the Atacama Desert. In doing so, a topological graph alignment of co-occurrence networks was used to determine the impact of a shift in environmental variables on OTUs taxonomic composition and their relationships. We observed that a fraction of association patterns identified in the co-occurrence networks are persistent despite large environmental variation. This apparent resilience seems to be due to: (1) a proportion of OTUs that persist across the gradient and maintain similar association patterns within the community and (2) bacterial community ecological rearrangements, where an important fraction of the OTUs come to fill the ecological roles of other OTUs in the other network. Actually, potential functional features suggest a fundamental role of persistent OTUs along the soil gradient involving nitrogen fixation. Our results allow identifying factors that induce changes in microbial assemblage configuration, altering specific bacterial soil functions and interactions within the microbial communities in natural environments.
Canine NAPEPLD-associated models of human myelin disorders
Authors: Minor K. M. , Letko A. , Becker D. , Drögemüller M. , Mandigers P. J. J. , Bellekom S. R. , Leegwater P. A. J. , Stassen Q. E. M. , Putschbach K. , Fischer A. , Flegel T. , Matiasek K. , Ekenstedt K. J. , Furrow E. , Patterson E. E. , Platt S. R. , Kelly P. A. , Cassidy J. P. , Shelton G. D. , Lucot K. , Bannasch D. L. , Martineau H. , Muir C. F. , Priestnall S. L. , Henke D. , Oevermann A. , Jagannathan V. , Mickelson J. R. , Drögemüller C. 
Published: April 2018

AbstractCanine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of theN-acyl phosphatidylethanolamine phospholipase D(NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this secondNAPEPLDvariant. The identification of differentNAPEPLDvariants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.
Annealing induced atomic rearrangements on (Ga,In) (N,As) probed by hard X-ray photoelectron spectroscopy and X-ray absorption fine structure
Authors: Ishikawa Fumitaro , Higashi Kotaro , Fuyuno Satoshi , Morifuji Masato , Kondow Masahiko , Trampert Achim 
Published: April 2018

AbstractWe study the effects of annealing on (Ga0.64,In0.36) (N0.045,As0.955) using hard X-ray photoelectron spectroscopy and X-ray absorption fine structure measurements. We observed surface oxidation and termination of the N-As bond defects caused by the annealing process. Specifically, we observed a characteristic chemical shift towards lower binding energies in the photoelectron spectra related to In. This phenomenon appears to be caused by the atomic arrangement, which produces increased In-N bond configurations within the matrix, as indicated by the X-ray absorption fine structure measurements. The reduction in the binding energies of group-III In, which occurs concomitantly with the atomic rearrangements of the matrix, causes the differences in the electronic properties of the system before and after annealing.
The sequence of cortical activity inferred by response latency variability in the human ventral pathway of face processing
Authors: Lin Jo-Fu Lotus , Silva-Pereyra Juan , Chou Chih-Che , Lin Fa-Hsuan 
Published: April 2018

AbstractVariability in neuronal response latency has been typically considered caused by random noise. Previous studies of single cells and large neuronal populations have shown that the temporal variability tends to increase along the visual pathway. Inspired by these previous studies, we hypothesized that functional areas at later stages in the visual pathway of face processing would have larger variability in the response latency. To test this hypothesis, we used magnetoencephalographic data collected when subjects were presented with images of human faces. Faces are known to elicit a sequence of activity from the primary visual cortex to the fusiform gyrus. Our results revealed that the fusiform gyrus showed larger variability in the response latency compared to the calcarine fissure. Dynamic and spectral analyses of the latency variability indicated that the response latency in the fusiform gyrus was more variable than in the calcarine fissure between 70 ms and 200 ms after the stimulus onset and between 4 Hz and 40 Hz, respectively. The sequential processing of face information from the calcarine sulcus to the fusiform sulcus was more reliably detected based on sizes of the response variability than instants of the maximal response peaks. With two areas in the ventral visual pathway, we show that the variability in response latency across brain areas can be used to infer the sequence of cortical activity.