bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
Authors: Sakalauskas Andrius , Ziaunys Mantas , Smirnovas Vytautas 
Published: September 2020

AbstractAmyloidogenic protein assembly into insoluble fibrillar aggregates is linked with several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, affecting millions of people worldwide. The search for a potential anti-amyloid drug has led to the discovery of hundreds of compounds, none of which have passed all clinical trials. Gallic acid has been shown to both modulate factors leading to the onset of neurodegenerative disorders, as well as directly inhibit amyloid formation. However, the conditions under which this effect is seen could lead to oxidation of this polyphenol, likely changing its properties. Here we examine the effect of gallic acid and its oxidised form on the aggregation of a model amyloidogenic protein–insulin at low pH conditions. We show a vastly higher inhibitory potential of the oxidised form, as well as an alteration in the aggregation pathway, leading to the formation of a specific fibril conformation.
A novel method for live imaging of human airway cilia using wheat germ agglutinin
Authors: Nakamura Ryosuke , Katsuno Tatsuya , Kishimoto Yo , Kaba Shinji , Yoshimatsu Masayoshi , Kitamura Morimasa , Suehiro Atsushi , Hiwatashi Nao , Yamashita Masaru , Tateya Ichiro , Omori Koichi 
Published: September 2020

AbstractMulticiliated epithelial cells in the airway are essential for mucociliary clearance. Their function relies on coordinated, metachronal and directional ciliary beating, appropriate mucus secretion and airway surface hydration. However, current conventional methods for observing human airway ciliary movement require ciliated cells to be detached from airway tissues. Determining the directionality of cilia is difficult. We developed a novel method to stain airway epithelial cilia to observe their movement without releasing ciliated cells. Human tracheae were obtained from patients (n = 13) who underwent laryngectomies to treat malignancies or swallowing disorders. The tracheae were treated with fluorescently labeled wheat germ agglutinin, which interacts with the acidic mucopolysaccharides present on the cilia. Epithelial surfaces were observed using an epi-fluorescence microscope equipped with a water-immersion objective lens and a high-speed camera. Ciliary movement was observable at 125 fps (13/13 samples). Ciliated cells in close proximity mostly exhibited well-coordinated ciliary beats with similar directionalities. These findings indicated that wheat germ agglutinin renders ciliary beats visible, which is valuable for observing human airway ciliary movements in situ.
Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy
Authors: Chen Minmin , Hu Jinxia , Wang Lujing , Li Yanru , Zhu Chenghao , Chen Chen , Shi Ming , Ju Zhicheng , Cao Xichuan , Zhang Zhuoqi 
Published: September 2020

AbstractIn this work, we developed a new antibody-targeted and redox-responsive drug delivery system “MSNs-CAIX” by binding the anti-carbonic anhydrase IX antibody (A-CAIX Ab) on the surface of mesoporous silica nanoparticles (MSNs) via disulfide linkages. The design of the composite particles “MSNs-CAIX” involved the synthesis and surface functionalization with thiol groups, 2,2′-dipyridyl disulfide and CAIX antibody. In vitro, CAIX capping the doxorubicin hydrochloric (DOX)-loaded nanoparticles (DOX@MSNs-CAIX) exhibited effectively redox-responsive release in the presence of glutathione (GSH) owing to the cleavage of the disulfide bond. Compared with CAIX negative Mef cells (mouse embryo fibroblast), remarkably more DOX@MSNs-CAIX was internalized into CAIX positive 4T1 cells (mouse breast cancer cells) by receptor-mediation. Tumor targeting in vivo studies clearly demonstrated DOX@MSNs-CAIX accumulated in tumors and induced more tumor cells apoptosis in 4T1 tumor-bearing mice. With great potential, this drug delivery system is a promising candidate for targeted and redox-responsive cancer therapy.
An altered glial phenotype in the NL3R451C mouse model of autism
Authors: Matta Samantha M. , Moore Zachery , Walker Frederick Rohan , Hill-Yardin Elisa L. , Crack Peter J. 
Published: September 2020

AbstractAutism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here, we studied characteristics of microglia and astrocytes in the Neuroligin-3 (NL3R451C) mouse model of autism since these cell types are involved in regulating both immune and synapse function. We observed increased microglial density in the dentate gyrus (DG) of NL3R451C mice without morphological differences. In contrast, WT and NL3R451C mice had similar astrocyte density but astrocyte branch length, the number of branch points, as well as cell radius and area were reduced in the DG of NL3R451C mice. Because retraction of astrocytic processes has been linked to altered synaptic transmission and dendrite formation, we assessed for regional changes in pre- and postsynaptic protein expression in the cortex, striatum and cerebellum in NL3R451C mice. NL3R451C mice showed increased striatal postsynaptic density 95 (PSD-95) protein levels and decreased cortical expression of synaptosomal-associated protein 25 (SNAP-25). These changes could contribute to dysregulated neurotransmission and cognition deficits previously reported in these mice.
Repeatability, reproducibility, and comparison of ocular biometry using a new optical coherence tomography-based system and another device
Authors: Wylęgała Adam , Bolek Bartłomiej , Mazur Robert , Wylęgała Edward 
Published: September 2020

AbstractPrecise measurement of axial length before cataract surgery is necessary for the proper lens implantation. We included 100 eyes of 56 patients in the study. The mean age was 41 (15–84 years). Measurements of axial length, anterior chamber depth (ACD) carried out with the new Revo NX were compared with those obtained with the IOLMaster 500. Interoperator testing was performed on 56 eyes of 56 participants. To test repeatability, axial length, ACD, central corneal thickness, and lens thickness were used. Inter-operator reproducibility was also assessed. The results were evaluated using Bland–Altman analyses. The mean ACD measured with the IOLMaster and Revo NX was 3.41 and 3.40 mm p = 0.467, respectively. The interclass correlation was excellent at the level of 0.975. ICC for axial length values was 0.999, and the mean was equal to 23.47 for the new device and 23.48 for IOLMaster. ICC for Inter-operator repeatability was higher than 0.99 in all parameters. Revo NX showed a very high level of repeatability with ICC ranging from 0.9929 for central corneal thickness to 0.9997 for axial length. Both devices showed excellent agreement and differences that are insignificant, which suggests that they can be used interchangeably.
The operational model of allosteric modulation of pharmacological agonism
Authors: Jakubík Jan , Randáková Alena , Chetverikov Nikolai , El-Fakahany Esam E. , Doležal Vladimír 
Published: September 2020

AbstractProper determination of agonist efficacy is indispensable in the evaluation of agonist selectivity and bias to activation of specific signalling pathways. The operational model (OM) of pharmacological agonism is a useful means for achieving this goal. Allosteric ligands bind to receptors at sites that are distinct from those of endogenous agonists that interact with the orthosteric domain on the receptor. An allosteric modulator and an orthosteric agonist bind simultaneously to the receptor to form a ternary complex, where the allosteric modulator affects the binding affinity and operational efficacy of the agonist. Allosteric modulators are an intensively studied group of receptor ligands because of their selectivity and preservation of physiological space–time pattern of the signals they modulate. We analysed the operational model of allosterically-modulated agonism (OMAM) including modulation by allosteric agonists. Similar to OM, several parameters of OMAM are inter-dependent. We derived equations describing mutual relationships among parameters of the functional response and OMAM. We present a workflow for the robust fitting of OMAM to experimental data using derived equations.
Dose–response assessment by quantitative MRI in a phase 1 clinical study of the anti-cancer vascular disrupting agent crolibulin
Authors: Lorza Andres M. Arias , Ravi Harshan , Philip Rohit C. , Galons Jean-Philippe , Trouard Theodore P. , Parra Nestor A. , Von Hoff Daniel D. , Read William L. , Tibes Raoul , Korn Ronald L. , Raghunand Natarajan 
Published: September 2020

AbstractThe vascular disrupting agent crolibulin binds to the colchicine binding site and produces anti-vascular and apoptotic effects. In a multisite phase 1 clinical study of crolibulin (NCT00423410), we measured treatment-induced changes in tumor perfusion and water diffusivity (ADC) using dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI), and computed correlates of crolibulin pharmacokinetics. 11 subjects with advanced solid tumors were imaged by MRI at baseline and 2–3 days post-crolibulin (13–24 mg/m2). ADC maps were computed from DW-MRI. Pre-contrast T1 maps were computed, co-registered with the DCE-MRI series, and maps of area-under-the-gadolinium-concentration-curve-at-90 s (AUC90s) and the Extended Tofts Model parameters ktrans, ve, and vp were calculated. There was a strong correlation between higher plasma drug $${C}^{max}$$

C

max

and a linear combination of (1) reduction in tumor fraction with $${AUC}_{90s}>15.8$$

AUC

90
s

>
15.8

mM s, and, (2) increase in tumor fraction with $${v}_{e}<0.3$$

v
e

<
0.3

. A higher plasma drug AUC was correlated with a linear combination of (1) increase in tumor fraction with $${\text{ADC}} < 1.1 \times 10^{ - 3} \;{\text{mm}}^{2} /{\text{s}}$$

ADC
<
1.1
×

10

-
3

mm

2

/
s

, and, (2) increase in tumor fraction with $$v_{e}<0.3$$

v
e

<
0.3

. These findings are suggestive of cell swelling and decreased tumor perfusion 2–3 days post-treatment with crolibulin. The multivariable linear regression models reported here can inform crolibulin dosing in future clinical studies of crolibulin combined with cytotoxic or immune-oncology agents.
Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2
Authors: Abrantes Joana , Droillard Clément , Lopes Ana M. , Lemaitre Evelyne , Lucas Pierrick , Blanchard Yannick , Marchandeau Stéphane , Esteves Pedro J. , Le Gall-Reculé Ghislaine 
Published: September 2020

AbstractRabbit haemorrhagic disease is a viral disease that emerged in the 1980s and causes high mortality and morbidity in the European rabbit (Oryctolagus cuniculus). In 2010, a new genotype of the rabbit haemorrhagic disease virus emerged and replaced the former circulating Lagovirus europaeus/GI.1 strains. Several recombination events have been reported for the new genotype Lagovirus europaeus/GI.2, with pathogenic (variants GI.1a and GI.1b) and benign (genotype GI.4) strains that served as donors for the non-structural part while GI.2 composed the structural part; another recombination event has also been described at the p16/p23 junction involving GI.4 strains. In this study, we analysed new complete coding sequences of four benign GI.3 strains and four GI.2 strains. Phylogenetic and recombination detection analyses revealed that the first GI.2 strains, considered as non-recombinant, resulted from a recombination event between GI.3 and GI.2, with GI.3 as the major donor for the non-structural part and GI.2 for the structural part. Our results indicate that recombination contributed to the emergence, persistence and dissemination of GI.2 as a pathogenic form and that all described GI.2 strains so far are the product of recombination. This highlights the need to study full-genomic sequences of lagoviruses to understand their emergence and evolution.
Simultaneous targeting of mitochondria and monocytes enhances neuroprotection against ischemia–reperfusion injury
Authors: Okahara Arihide , Koga Jun-ichiro , Matoba Tetsuya , Fujiwara Masaki , Tokutome Masaki , Ikeda Gentaro , Nakano Kaku , Tachibana Masaki , Ago Tetsuro , Kitazono Takanari , Tsutsui Hiroyuki , Egashira Kensuke 
Published: September 2020

AbstractIschemia–reperfusion injury impairs the efficacy of reperfusion therapy after ischemic stroke. Cyclophilin D (CypD)-mediated openings of mitochondrial permeability transition pore (mPTP) and subsequent monocyte-mediated inflammation are considered as major mechanisms of reperfusion injury. However, no medical therapies are currently available. Therefore, we have tested a hypothesis that simultaneous targeting of mPTP and inflammation confers substantial neuroprotection after cerebral ischemia–reperfusion. To address this point, we prepared CypD knockout mice, C–C chemokine receptor 2 (CCR2) knockout mice and CypD/CCR2 double knockout mice. These mice were subjected to 60 min transient cerebral ischemia by occluding middle cerebral arteries. Neurological deficits evaluated 3 days after reperfusion were significantly attenuated in CypD/CCR2 double knockout mice as compared to wild-type mice and other single knockout mice. Then, we have prepared polymeric nanoparticles containing cyclosporine A (CsA-NPs) and pitavastatin (Pitava-NPs), targeting mPTP opening and inflammation, respectively. Simultaneous administration of CsA-NP and Pitava-NP at the time of reperfusion also decreased infarct size and attenuated neurological deficits as compared to control nanoparticles and single administration of CsA-NPs or Pitava-NPs. These results indicate that simultaneous targeting of the mPTP opening and monocyte-mediated inflammation could be a novel strategy for better neurological outcomes in patients with ischemic stroke.
Metabolic alterations in Parkinson’s disease astrocytes
Authors: Sonninen Tuuli-Maria , Hämäläinen Riikka H. , Koskuvi Marja , Oksanen Minna , Shakirzyanova Anastasia , Wojciechowski Sara , Puttonen Katja , Naumenko Nikolay , Goldsteins Gundars , Laham-Karam Nihay , Lehtonen Marko , Tavi Pasi , Koistinaho Jari , Lehtonen Šárka 
Published: September 2020

AbstractIn Parkinson`s disease (PD), the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta is associated with Lewy bodies arising from the accumulation of alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a disease of the DA neurons, a glial contribution, in particular that of astrocytes, in PD pathogenesis is starting to be uncovered. Here, we report findings from astrocytes derived from induced pluripotent stem cells of LRRK2 G2019S mutant patients, with one patient also carrying a GBA N370S mutation, as well as healthy individuals. The PD patient astrocytes manifest the hallmarks of the disease pathology including increased expression of alpha-synuclein. This has detrimental consequences, resulting in altered metabolism, disturbed Ca2+ homeostasis and increased release of cytokines upon inflammatory stimulation. Furthermore, PD astroglial cells manifest increased levels of polyamines and polyamine precursors while lysophosphatidylethanolamine levels are decreased, both of these changes have been reported also in PD brain. Collectively, these data reveal an important role for astrocytes in PD pathology and highlight the potential of iPSC-derived cells in disease modeling and drug discovery.
Effects of short-time exposure of surface pre-reacted glass-ionomer eluate on dental microcosm biofilm
Authors: Kim Hyo-Jung , Cho Mu-Yeol , Lee Eun-Song , Jung Hoi In , Kim Baek-Il 
Published: September 2020

AbstractThis study evaluated the antibacterial effects of short-time exposure of surface pre-reacted glass-ionomer (S-PRG) eluate on oral microcosm biofilm. Biofilms were treated with an S-PRG eluate at different concentrations (25%, 50%, and 100%), distilled water (DW), and 0.1% chlorhexidine (CHX) twice a day for 5 min repeatedly. After 7 days, the total and aciduric bacterial counts and biofilm dry weights were measured. An image analysis program calculated the red/green (R/G) ratios in the biofilm autofluorescence images. Microscopic analyses quantified the biofilm thickness and live/dead cell ratio and determined morphological changes in the biofilm. Bacterial counts and dry weights were not significantly different in the DW group for all S-PRG eluate concentrations. An increasing trend in the R/G ratio for 7 days biofilm treatment was observed for the S-PRG eluate and the DW groups. Furthermore, the live/dead cell ratios in the biofilm and the biofilm thickness of the S-PRG eluate groups were similar to those of the DW group. The bacteria morphology inside the biofilm changed only in the CHX group. Short-time S-PRG eluate treatment showed no significant antibacterial and antibiofilm effects. These results indicated that limited biofilm formation inhibition can be obtained by using only the S-PRG eluate.
Surface reconstruction and band bending in hydrogen-adsorbed $$\hbox {Bi}_2\hbox {Se}_3$$ topological insulator
Authors: Lee Kyu Won , Lee Cheol Eui 
Published: September 2020

AbstractWe have investigated the effects of hydrogen adsorption on the $$\hbox {Bi}_2\hbox {Se}_3$$

Bi
2

Se
3

topological insulator by using the density functional theory calculations. We found that hydrogen adsorption on the surface leads to surface reconstruction to reduce the band bending effect. Contrasting to a previous report that hydrogen adsorption transforms the single Dirac cone at the Brillouin zone center into three Dirac cones at the zone boundary, the Dirac cones at the zone center corresponding to the topological surface states were confirmed to be robust against the hydrogen adsorption and surface reconstruction. Hydrogen adsorption induces a Rashba-like spin-splitting of the topological surface state, and can introduce Rashba-like quantum well states within the bulk gap, which can be attributed to a semiconductor-like band bending at an interface.
Impaired brain homeostasis and neurogenesis in diet-induced overweight zebrafish: a preventive role from A. borbonica extract
Authors: Ghaddar Batoul , Veeren Bryan , Rondeau Philippe , Bringart Matthieu , Lefebvre d’Hellencourt Christian , Meilhac Olivier , Bascands Jean-Loup , Diotel Nicolas 
Published: September 2020

AbstractOverweight and obesity are worldwide health concerns leading to many physiological disorders. Recent data highlighted their deleterious effects on brain homeostasis and plasticity, but the mechanisms underlying such disruptions are still not well understood. In this study, we developed and characterized a fast and reliable diet-induced overweight (DIO) model in zebrafish, for (1) studying the effects of overfeeding on brain homeostasis and for (2) testing different preventive and/or therapeutic strategies. By overfeeding zebrafish for 4 weeks, we report the disruption of many metabolic parameters reproducing human overweight features including increased body weight, body mass index, fasting blood glucose levels and liver steatosis. Furthermore, DIO fish displayed blood–brain barrier leakage, cerebral oxidative stress, neuroinflammation and decreased neurogenesis. Finally, we investigated the preventive beneficial effects ofA. borbonica, an endogenous plant from Reunion Island. Overnight treatment withA. borbonicaaqueous extract during the 4 weeks of overfeeding limited some detrimental central effects of DIO. In conclusion, we established a relevant DIO model in zebrafish demonstrating that overfeeding impairs peripheral and central homeostasis. This work also highlights the preventive protective effects ofA. borbonicaaqueous extracts in DIO, and opens a way to easily screen drugs aiming at limiting overweight and associated neurological disorders.
Mosquito repellence induced by tarsal contact with hydrophobic liquids
Authors: Iikura Hiroaki , Takizawa Hiroyuki , Ozawa Satoshi , Nakagawa Takao , Matsui Yoshiaki , Nambu Hiromi 
Published: September 2020

AbstractMosquito legs have a unique highly water-repellent surface structure. While being beneficial to mosquitoes, the water-repellence of the tarsi enhances the wettability of hydrophobic substances such as oils. This high wettability induces strong attraction forces on a mosquito’s legs (up to 87% of the mosquito’s weight) towards the oil. We studied the landing behaviour of mosquitoes on oil-coated surfaces and observed that the mosquito contact time was reduced compared to that on hydrophilic-liquid-coated surfaces, suggesting that the oil coating induces an escape response. The observed escape behaviour occurred consistently with several hydrophobic liquids, including silicone oil, which is used globally in personal care products. As the repellent effect is similar to multiple hydrophobic substances, it is likely to be mechanically stimulated owing to the physical properties of the hydrophobic liquids and not due to chemical interactions. On human skin, the contact time was sufficiently short to prevent mosquitoes from starting to blood-feed. The secretion of Hippopotamus amphibius, which has physical properties similar to those of low-viscosity silicone oil, also triggered an escape response, suggesting that it acts as a natural mosquito repellent. Our results are beneficial to develop new, safe, and effective mosquito-repellent technologies.
Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
Authors: Wongtrakul Jeerang , Thongtan Thananya , Pannengpetch Supitcha , Wikan Nitwara , Kantamala Doungnapa , Kumrapich Benjawan , Suwan Warissara , Smith Duncan R. 
Published: September 2020

AbstractDengue virus (DENV) is an arthropod-borne Flavivirus that can cause a range of symptomatic disease in humans. There are four dengue viruses (DENV 1 to 4) and infection with one DENV only provides transient protection against a heterotypic virus. Second infections are often more severe as the disease is potentiated by antibodies from the first infection through a process known as antibody dependent enhancement (ADE) of infection. Phosphorylation is a major post-translational modification that can have marked effects on a number of processes. To date there has been little information on the phosphorylation changes induced by DENV infection. This study aimed to determine global phosphoproteome changes induced by DENV 2 in U937 cells infected under an ADE protocol. A 2-dimensional electrophoretic approach coupled with a phosphoprotein-specific dye and mass spectroscopic analysis identified 15 statistically significant differentially phosphorylated proteins upon DENV 2 infection. One protein identified as significantly differentially phosphorylated, pyruvate kinase M2 (PKM2) was validated. Treatment with a PKM2 inhibitor modestly reduced levels of infection and viral output, but no change was seen in cellular viral protein levels, suggesting that PKM2 acts on exocytic virus release. While the effect of inhibition of PKM2 was relatively modest, the results highlight the need for a greater understanding of the role of phosphoproteins in DENV infection.