bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional brain networks in the schizophrenia spectrum and bipolar disorder with psychosis
Authors: van Dellen Edwin , Börner Corinna , Schutte Maya , van Montfort Simone , Abramovic Lucija , Boks Marco P. , Cahn Wiepke , van Haren Neeltje , Mandl René , Stam Cornelis J. , Sommer Iris
Published: September 2020

Psychotic experiences have been proposed to lie on a spectrum, ranging from subclinical experiences to treatment-resistant schizophrenia. We aimed to characterize functional connectivity and brain network characteristics in relation to the schizophrenia spectrum and bipolar disorder with psychosis to disentangle neural correlates to psychosis. Additionally, we studied antipsychotic medication and lithium effects on network characteristics. We analyzed functional connectivity strength and network topology in 487 resting-state functional MRI scans of individuals with schizophrenia spectrum disorder (SCZ), bipolar disorder with a history of psychotic experiences (BD), treatment-naïve subclinical psychosis (SCP), and healthy controls (HC). Since differences in connectivity strength may confound group comparisons of brain network topology, we analyzed characteristics of the minimum spanning tree (MST), a relatively unbiased backbone of the network. SCZ and SCP subjects had a lower connectivity strength than BD and HC individuals but showed no differences in network topology. In contrast, BD patients showed a less integrated network topology but no disturbances in connectivity strength. No differences in outcome measures were found between SCP and SCZ, or between BD patients that used antipsychotic medication or lithium and those that did not. We conclude that functional networks in patients prone to psychosis have different signatures for chronic SCZ patients and SCP compared to euthymic BD patients, with a limited role for medication. Connectivity strength effects may have confounded previous studies, as no functional network alterations were found in SCZ after strict correction for connectivity strength.
Dynamic control of heat flow using a spin-chain ladder cuprate film and an ionic liquid
Authors: Terakado Nobuaki , Nara Yoshinori , Machida Yuki , Takahashi Yoshihiro , Fujiwara Takumi
Published: September 2020

Dynamic control of heat flow for applications in thermal management has attracted much interest in fields such as electronics and thermal engineering. Spin-chain ladder cuprates are promising materials to realize dynamic control of heat flow, since their magnon thermal conductivity is sensitive to the hole density in the spin ladders, which can be dynamically controlled by an external field. Here, we demonstrate the electric control of heat flow using a polycrystalline cuprate film and an ionic liquid. The results showed that a voltage application to the interface causes imperfectly recoverable decreases in both the thermal conductance of the film and the peak due to magnons in the Raman spectra. This result may be attributed to an increase in the hole density in the spin ladders. This report highlights that magnon thermal conduction has potential for the development of advanced thermal management applications.
Carbohydrate knowledge, dietary guideline awareness, motivations and beliefs underlying low-carbohydrate dietary behaviours
Authors: Churuangsuk Chaitong , Lean Michael E. J. , Combet Emilie
Published: September 2020

To explore the factors (including knowledge and attitude) influencing the decision to follow a low-carbohydrate diet (LCD) or not in a sample of the UK population. An online questionnaire was distributed electronically to adults who had either followed LCD or not (February–December 2019). Demographics and self-reported “LCD-status” (current, past and non-follower) were collected. Multivariable linear regression was used with carbohydrate knowledge, dietary guideline agreement and theory of planned behaviour (TPB) constructs (all as predictors) to explain the intention to follow a LCD (outcome). Respondents (n = 723, 71% women, median age 34; 85% white-ethnicity) were either following (n = 170, 24%) or had tried a LCD in the preceding 3 months (n = 184, 25%). Current followers had lower carbohydrate knowledge scores (1–2 point difference, scale − 11 to 11) than past and non-followers. A majority of current LCD followers disagreed with the EatWell guide recommendations “Base meals on potatoes, bread, rice and pasta, or other starchy carbohydrates. Choose whole grains where possible” (84%) and “Choose unsaturated oils and spreads and eat in small amounts such as vegetable, rapeseed, olive and sunflower oils” (68%) compared to past (37%, 10%, respectively) and non-followers (16%, 8%, respectively). Weight-loss ranked first as a motivation, and the internet was the most influencial source of information about LCDs. Among LCD-followers, 71% reported ≥ 5% weight loss, and over 80% did not inform their doctor, nurse, or dietitian about following a diet. Approximately half of LCD followers incorporated supplements to their diets (10% used multivitamin/mineral supplements), despite the restrictive nature of the diet. TPB constructs, carbohydrate knowledge, and guideline agreement explained 60% of the variance for the intention to follow a LCD. Attitude (std-β = 0.60), perceived behavioural control (std-β = 0.24) and subjective norm (std-β = 0.14) were positively associated with the intention to follow a LCD, while higher knowledge of carbohydrate, and agreeing with national dietary guidelines were both inversely associated (std-β = − 0.09 and − 0.13). The strongest primary reason behind UK adults’ following a LCD is to lose weight, facilitated by attitude, perceived behavioural control and subjective norm. Higher knowledge about carbohydrate and agreement with dietary guidelines are found among people who do not follow LCDs.
Using the transient trajectories of an optically levitated nanoparticle to characterize a stochastic Duffing oscillator
Authors: Flajšmanová Jana , Šiler Martin , Jedlička Petr , Hrubý František , Brzobohatý Oto , Filip Radim , Zemánek Pavel
Published: September 2020

We propose a novel methodology to estimate parameters characterizing a weakly nonlinear Duffing oscillator represented by an optically levitating nanoparticle. The method is based on averaging recorded trajectories with defined initial positions in the phase space of nanoparticle position and momentum and allows us to study the transient dynamics of the nonlinear system. This technique provides us with the parameters of a levitated nanoparticle such as eigenfrequency, damping, coefficient of nonlinearity and effective temperature directly from the recorded transient particle motion without any need for external driving or modification of an experimental system. Comparison of this innovative approach with a commonly used method based on fitting the power spectrum density profile shows that the proposed complementary method is applicable even at lower pressures where the nonlinearity starts to play a significant role and thus the power spectrum density method predicts steady state parameters. The technique is applicable also at low temperatures and extendable to recent quantum experiments. The proposed method is applied on experimental data and its validity for one-dimensional and three-dimensional motion of a levitated nanoparticle is verified by extensive numerical simulations.
Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
Authors: Sakalauskas Andrius , Ziaunys Mantas , Smirnovas Vytautas
Published: September 2020

Amyloidogenic 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

Multiciliated 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

In 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

Autism 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

Precise 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

Proper 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

The 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

Rabbit 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

Ischemia–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

In 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

This 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

We 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

Overweight 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

Mosquito 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

Dengue 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.
Ca2+-activated KCa3.1 potassium channels contribute to the slow afterhyperpolarization in L5 neocortical pyramidal neurons
Authors: Roshchin M. V. , Ierusalimsky V. N. , Balaban P. M. , Nikitin E. S.
Published: September 2020

Layer 5 neocortical pyramidal neurons are known to display slow Ca2+-dependent afterhyperpolarization (sAHP) after bursts of spikes, which is similar to the sAHP in CA1 hippocampal cells. However, the mechanisms of sAHP in the neocortex remain poorly understood. Here, we identified the Ca2+-gated potassium KCa3.1 channels as contributors to sAHP in ER81-positive neocortical pyramidal neurons. Moreover, our experiments strongly suggest that the relationship between sAHP and KCa3.1 channels in a feedback mechanism underlies the adaptation of the spiking frequency of layer 5 pyramidal neurons. We demonstrated the relationship between KCa3.1 channels and sAHP using several parallel methods: electrophysiology, pharmacology, immunohistochemistry, and photoactivatable probes. Our experiments demonstrated that ER81 immunofluorescence in layer 5 co-localized with KCa3.1 immunofluorescence in the soma. Targeted Ca2+ uncaging confirmed two major features of KCa3.1 channels: preferential somatodendritic localization and Ca2+-driven gating. In addition, both the sAHP and the slow Ca2+-induced hyperpolarizing current were sensitive to TRAM-34, a selective blocker of KCa3.1 channels.
Environmental regulations, green innovation and intelligent upgrading of manufacturing enterprises: evidence from China
Authors: Meng Fansheng , Xu Ye , Zhao Gang
Published: September 2020

Intelligent development is an inevitable choice for the green development of manufacturing enterprises, environmental regulations and green innovation play an important role in the intelligent development of manufacturing enterprises. By analyzing the interrelationships between environmental regulations, green innovation, environmental dynamism and the intelligent upgrading of manufacturing enterprises, this paper builds a model of the impact of environmental regulations on the intelligent upgrading of manufacturing enterprises. Taking the listed Chinese manufacturing enterprises that implement intelligent upgrades as the survey object, the concept model was verified. The results of the study show that environmental regulations, green innovation have a significant positive effect on intelligent upgrading of manufacturing enterprises. Furthermore, it reveals that green innovation plays a partially mediating role in the relationship between environmental regulations and the intelligent upgrading of manufacturing enterprises. Environmental dynamism have a positive adjustment effect between green innovation and the intelligent upgrading of manufacturing enterprises. The conclusion of the study deepens the relevant research on the intelligent upgrade of manufacturing enterprises, and provides theoretical basis and reference for the intelligent development of manufacturing enterprises.
The impact of the AMV on Eurasian summer hydrological cycle
Authors: Nicolì Dario , Bellucci Alessio , Iovino Doroteaciro , Ruggieri Paolo , Gualdi Silvio
Published: September 2020

Impact studies of the Atlantic Multidecadal Variability (AMV) on the climate system are severely limited by the lack of sufficiently long observational records. Relying on a model-based approach is therefore mandatory to overcome this limitation. Here, a novel experimental setup, designed in the framework of the CMIP6-endorsed Decadal Climate Prediction Project, is applied to the CMCC climate model to analyse the remote climate impact of the AMV on the Northern Eurasian continent. Model results show that, during Boreal summer, an enhanced warming associated to a positive phase of the AMV, induces a hemispheric-scale wave-train response in the atmospheric circulation, affecting vast portions of Northern Eurasia. The overall AMV-induced response consists in an upper-tropospheric anomalous flows leading to a rainfall increase over Scandinavia and Siberia and to an intensified river runoff by the major Siberian rivers. A strengthening of Eurasian shelves’ stratification, broadly consistent with the anomalous river discharge, is found in the proximity of the river mouths during positive-AMV years. Considering that Siberian rivers (Ob’, Yenisei and Lena) account for almost half of the Arctic freshwater input provided by terrestrial sources, the implications of these findings for decadal variability and predictability of the Arctic environment are also discussed.
A hydrodynamics assessment of the hammerhead shark cephalofoil
Authors: Gaylord Matthew K. , Blades Eric L. , Parsons Glenn R.
Published: September 2020

Hammerhead sharks are characterized by a conspicuous lateral expansion of the head forming a structure known as a cephalofoil. Two theories regarding the function of this structure suggest that it may increase maneuverability as well as produce dynamic lift similar to a cambered airplane wing. Here we report on a family-wide computational fluid dynamics analysis of all eight hammerhead shark species and three sharks with typical head shape. Models cast of the heads of fresh and museum specimens of hammerhead and typical sharks were used to produce pressure surface maps and lift and drag polar diagrams at various angles of attack. These analyses suggested that the cephalofoil (1) provides greater maneuverability that may be important in prey capture efficacy, (2) does not provide significant dynamic lift when held parallel to flow, (3) is characterized by greater drag than typical sharks across all attack angles, and (4) was found to result in a 10-x increase in energetic cost over typical shark head morphologies.
VEGF-A splice variants bind VEGFRs with differential affinities
Authors: Mamer Spencer B. , Wittenkeller Ashley , Imoukhuede P. I.
Published: September 2020

Vascular endothelial growth factor A (VEGF-A) and its binding to VEGFRs is an important angiogenesis regulator, especially the earliest-known isoform, VEGF-A165a. Yet several additional splice variants play prominent roles in regulating angiogenesis in health and in vascular disease, including VEGF-A121 and an anti-angiogenic variant, VEGF-A165b. Few studies have attempted to distinguish these forms from their angiogenic counterparts, experimentally. Previous studies of VEGF-A:VEGFR binding have measured binding kinetics for VEGFA165 and VEGF-A121, but binding kinetics of the other two pro- and all anti-angiogenic splice variants are not known. We measured the binding kinetics for VEGF-A165, -A165b, and -A121 with VEGFR1 and VEGF-R2 using surface plasmon resonance. We validated our methods by reproducing the known affinities between VEGF-A165a:VEGFR1 and VEGF-A165a:VEGFR2, 1.0 pM and 10 pM respectively, and validated the known affinity VEGF-A121:VEGFR2 as KD = 0.66 nM. We found that VEGF-A121 also binds VEGFR1 with an affinity KD = 3.7 nM. We further demonstrated that the anti-angiogenic variant, VEGF-A165b selectively prefers VEGFR2 binding at an affinity = 0.67 pM while binding VEGFR1 with a weaker affinity—KD = 1.4 nM. These results suggest that the − A165b anti-angiogenic variant would preferentially bind VEGFR2. These discoveries offer a new paradigm for understanding VEGF-A, while further stressing the need to take care in differentiating the splice variants in all future VEGF-A studies.
A training algorithm for networks of high-variability reservoirs
Authors: Freiberger Matthias , Bienstman Peter , Dambre Joni
Published: September 2020

Physical reservoir computing approaches have gained increased attention in recent years due to their potential for low-energy high-performance computing. Despite recent successes, there are bounds to what one can achieve simply by making physical reservoirs larger. Therefore, we argue that a switch from single-reservoir computing to multi-reservoir and even deep physical reservoir computing is desirable. Given that error backpropagation cannot be used directly to train a large class of multi-reservoir systems, we propose an alternative framework that combines the power of backpropagation with the speed and simplicity of classic training algorithms. In this work we report our findings on a conducted experiment to evaluate the general feasibility of our approach. We train a network of 3 Echo State Networks to perform the well-known NARMA-10 task, where we use intermediate targets derived through backpropagation. Our results indicate that our proposed method is well-suited to train multi-reservoir systems in an efficient way.
Human serum albumin as a clinically accepted cell carrier solution for skin regenerative application
Authors: Shahin Hady , Elmasry Moustafa , Steinvall Ingrid , Markland Katrin , Blomberg Pontus , Sjöberg Folke , El-Serafi Ahmed T.
Published: September 2020

The rules governing Medicinal Products in the European Union necessitates the production of cell-based therapy in good manufacturing practice facilities. The produced cells may need several hours in transportation to reach the application sites. In this study, we investigated four candidate solutions for transporting human keratinocytes. The solutions are (1) normal saline, (2) saline with 2.5% human serum albumin (Saline + HSA), (3) chemically defined, xeno-free keratinocyte media and (4) keratinocyte media with pituitary bovine extract (PBE-media). One million keratinocytes from three donors were suspended in each solution and kept at 4 °C for up to 24 h. Cells kept in Saline + HSA showed higher viability after 1, 3 and 24 h. Then, equal number of viable cells were seeded on collagenous matrix and cultured for 48 h. The adhesion and colonization were higher in the cells kept in PBE-media, while the keratinocyte surface marker, cytokeratin 14, was present in all studied groups. These results confirmed the suitability of Saline + HSA as a cell transportation solution for clinical use, which will be the choice for the planned clinical trial. Keratinocyte PBE-media can be an alternative for cells transported for research purpose, if the same media type is going to be used in the following experiments.
Liver dysfunction is associated with poor prognosis in patients after immune checkpoint inhibitor therapy
Authors: Yokohama Keisuke , Asai Akira , Matsui Masahiro , Okamoto Norio , Yasuoka Hidetaka , Nishikawa Tomohiro , Ohama Hideko , Tsuchimoto Yusuke , Inoue Yoshihiro , Fukunishi Shinya , Uchiyama Kazuhisa , Higuchi Kazuhide
Published: September 2020

Immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors (ICIs). Liver is one of the main target organs which irAEs occur and we investigated the influence of liver dysfunction on prognosis of patients after ICIs. From July 2014 to December 2018, 188 patients with diverse cancers who received ICIs (nivolumab or pembrolizumab) were enrolled. Twenty-nine patients experienced liver dysfunction of any grades after ICIs. Progression-free survival (PFS) was significantly shorter in the liver dysfunction-positive group than in the liver dysfunction-negative group, and a similar result was obtained for Overall survival (OS). Multiple logistic regression analysis revealed liver metastasis and alanine aminotransferase before ICIs were associated with a higher incidence of liver dysfunction after ICIs. Regardless of liver metastasis, PFS and OS were significantly shorter in the liver dysfunction-positive group. In conclusion, this study suggests liver dysfunction is associated with poor prognosis in patients after ICIs with diverse cancers.
Schisandrin B regulates MC3T3-E1 subclone 14 cells proliferation and differentiation through BMP2-SMADs-RUNX2-SP7 signaling axis
Authors: Wang Xueni , Liao Xiuling , Zhang Yimin , Wei Linyao , Pang Yuzhou
Published: September 2020

Schisandrin B (SchB) is the highest content of biphenyl cyclooctene lignans in Schisandra chinensis. It has been reported to have a variety of pharmacological effects, including anti-inflammatory, anti-oxidant, anti-cancer, heart protection, liver protection. In this study, we found that SchB can promote the proliferation of MC3T3-E1 subclone 14 cells. Meanwhile, we found that SchB can regulate the BMP2-SMADs signaling pathway by increasing gene and protein expression of those relative biomolecules. Furthermore, SchB can raise the RUNX2 and SP7 expression in both mRNA and protein levels. Since the role of BMP2-SMADs-RUNX2-SP7 signaling axis in osteoblast proliferation and differentiation has been well documented. The present experimental findings indicate that SchB could promote the proliferation and differentiation of osteoblasts through BMP2-SMADs-RUNX2-SP7 signaling axis.
Formation of oriented fishbone-like pores in biodegradable polymer scaffolds using directional phase-separation processing
Authors: Ko Young Gun
Published: September 2020

The scaffold is a dreamed biomaterial of tissue engineers which can culture cells three-dimensionally outgrowing the two-dimensional cell culture in a petri dish to repair or regenerate tissues and organs. To maximize the performance of this dreamed material, complex three-dimensional (3D) structures should be generated with a simple technique and nontoxic ingredients. Many tissues have tubular or fibrous bundle architectures such as nerve, muscle, tendon, ligament, blood vessel, bone and teeth. The concept of mimicking the extracellualr matrix in real tissue has recently been applied to scaffold development. In this study, a novel method for preparing the poly(l-lactic acid) (PLLA) scaffold with a tubular architecture is presented. Solid–liquid phase-separation was applied to form tubular pores in the scaffold using the directional freezing apparatus. Pores formed in this manner exhibited a fishbone like morphology due to the two crystalline phases of 1,4-dioxane. A tubular diameter of ca. 60–250 μm was achieved by regulating the PLLA concentration and the cooling rate. The compressive modulus of the fishbone-like porous scaffold showed higher values than that of non-directional porous scaffold.
Hippocampal alterations in glutamatergic signaling during amyloid progression in AβPP/PS1 mice
Authors: Hascup Kevin N. , Findley Caleigh A. , Sime Lindsey N. , Hascup Erin R.
Published: September 2020

Our previous research demonstrated that soluble amyloid-β (Aβ)42, elicits presynaptic glutamate release. We hypothesized that accumulation and deposition of Aβ altered glutamatergic neurotransmission in a temporally and spatially dependent manner. To test this hypothesis, a glutamate selective microelectrode array (MEA) was used to monitor dentate (DG), CA3, and CA1 hippocampal extracellular glutamate levels in 2–4, 6–8, and 18–20 month-old male AβPP/PS1 and age-matched C57BL/6J control mice. Starting at 6 months of age, AβPP/PS1 basal glutamate levels are elevated in all three hippocampal subregions that becomes more pronounced at the oldest age group. Evoked glutamate release was elevated in all three age groups in the DG, but temporally delayed to 18–20 months in the CA3 of AβPP/PS1 mice. However, CA1 evoked glutamate release in AβPP/PS1 mice was elevated at 2–4 months of age and declined with age. Plaque deposition was anatomically aligned (but temporally delayed) with elevated glutamate levels; whereby accumulation was first observed in the CA1 and DG starting at 6–8 months that progressed throughout all hippocampal subregions by 18–20 months of age. The temporal hippocampal glutamate changes observed in this study may serve as a biomarker allowing for time point specific therapeutic interventions in Alzheimer’s disease patients.
Virtual care models for cancer survivorship
Authors: Pham Quynh , Hearn Jason , Gao Bruce , Brown Ian , Hamilton Robert J. , Berlin Alejandro , Cafazzo Joseph A. , Feifer Andrew
Published: September 2020

Virtual care models for cancer survivorship are needed to support patients living with the chronic effects of cancer treatment, while increasing health system capacity. Characteristics that may be critical to their success have not been adequately studied. This scoping review summarizes previous efforts to virtualize survivorship care to inform future innovations in the field. Four databases were searched for articles published before January 2020, and 24 articles that met selection criteria were included in this analysis. Rationale for pursuing virtual models of care shared two common objectives: (1) the need for sustainable survivorship care, and (2) the opportunity to improve survivorship outcomes. Breast cancer (N = 10) and prostate cancer (N = 4) were the most targeted cancers for virtual survivorship care. The implemented technologies included web platforms (N = 15), telephone calls (N = 12), and smartphone or tablet applications (N = 5). A variety of healthcare professionals were effectively involved in the provision of virtual care. Future virtual care models may benefit from integrating with existing health systems and services, repurposing common technologies, involving allied health professionals, and engaging patients and caregivers from diverse communities in the design of virtual services.