bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of Hall effect and Ion slip in a three-dimensional bioconvective Tangent hyperbolic nanofluid flow subject to Arrhenius activation energy
Authors: Ramzan Muhammad , Gul Hina , Chung Jae Dong , Kadry Seifedine , Chu Yu-Ming
Published: October 2020

The dynamics of partially ionized fluid flow subjected to the magnetic field are altogether distinct in comparison to the flow of natural fluids. Fewer studies are available in the literature discussing the alluring characteristics of the Hall effect and the Ion slip in nanofluid flows. Nevertheless, the flow of nanofluid flow with Hall and Ion slip effect integrated with activation energy, gyrotactic microorganisms, and Cattaneo–Christov heat flux is still scarce. To fill in this gap, our aim here is to examine the three dimensional electrically conducting Tangent hyperbolic bioconvective nanofluid flow with Hall and Ion slip under the influence of magnetic field and heat transmission phenomenon past a stretching sheet. Impacts of Cattaneo–Christov heat flux, Arrhenius activation energy, and chemical reaction are also considered here. For the conversion of a non-linear system to an ordinary one, pertinent transformations procedure is implemented. By using the bvp4c MATLAB function, these equations with the boundary conditions are worked out numerically. The significant impacts of prominent parameters on velocity, temperature, and concentration profiles are investigated through graphical illustrations. The results show that the velocity of the fluid is enhanced once the Ion slip and Hall parameters values are improved. Furthermore, the concentration is improved when the values of the activation energy parameter are enhanced.
Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome
Authors: Mindikoglu Ayse L. , Abdulsada Mustafa M. , Jain Antrix , Jalal Prasun K. , Devaraj Sridevi , Wilhelm Zoe R. , Opekun Antone R. , Jung Sung Yun
Published: October 2020

Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry. We found a significant fold increase in the levels of several tumor suppressor and DNA repair gene protein products (GP)s at the end of 4th week during 4-week intermittent fasting (CALU, INTS6, KIT, CROCC, PIGR), and 1 week after 4-week intermittent fasting (CALU, CALR, IGFBP4, SEMA4B) compared with the levels before 4-week intermittent fasting. We also found a significant reduction in the levels of tumor promoter GPs at the end of 4th week during 4-week intermittent fasting (POLK, CD109, CAMP, NIFK, SRGN), and 1 week after 4-week intermittent fasting (CAMP, PLAC1) compared with the levels before 4-week intermittent fasting. Fasting from dawn to sunset for four weeks also induced an anti-diabetes proteome response by upregulating the key regulatory proteins of insulin signaling at the end of 4th week during 4-week intermittent fasting (VPS8, POLRMT, IGFBP-5) and 1 week after 4-week intermittent fasting (PRKCSH), and an anti-aging proteome response by upregulating H2B histone proteins 1 week after 4-week intermittent fasting. Subjects had a significant reduction in body mass index, waist circumference, and improvement in blood pressure that co-occurred with the anticancer, anti-diabetes, and anti-aging serum proteome response. These findings suggest that intermittent fasting from dawn to sunset actively modulates the respective genes and can be an adjunct treatment in metabolic syndrome. Further studies are needed to test the intermittent fasting from dawn to sunset in the prevention and treatment of metabolic syndrome-induced cancers.
A missense mutation in the RSRSP stretch of Rbm20 causes dilated cardiomyopathy and atrial fibrillation in mice
Authors: Ihara Kensuke , Sasano Tetsuo , Hiraoka Yuichi , Togo-Ohno Marina , Soejima Yurie , Sawabe Motoji , Tsuchiya Megumi , Ogawa Hidesato , Furukawa Tetsushi , Kuroyanagi Hidehito
Published: October 2020

Dilated cardiomyopathy (DCM) is a fatal heart disease characterized by left ventricular dilatation and cardiac dysfunction. Recent genetic studies on DCM have identified causative mutations in over 60 genes, including RBM20, which encodes a regulator of heart-specific splicing. DCM patients with RBM20 mutations have been reported to present with more severe cardiac phenotypes, including impaired cardiac function, atrial fibrillation (AF), and ventricular arrhythmias leading to sudden cardiac death, compared to those with mutations in the other genes. An RSRSP stretch of RBM20, a hotspot of missense mutations found in patients with idiopathic DCM, functions as a crucial part of its nuclear localization signals. However, the relationship between mutations in the RSRSP stretch and cardiac phenotypes has never been assessed in an animal model. Here, we show that Rbm20 mutant mice harboring a missense mutation S637A in the RSRSP stretch, mimicking that in a DCM patient, demonstrated severe cardiac dysfunction and spontaneous AF and ventricular arrhythmias mimicking the clinical state in patients. In contrast, Rbm20 mutant mice with frame-shifting deletion demonstrated less severe phenotypes, although loss of RBM20-dependent alternative splicing was indistinguishable. RBM20S637A protein cannot be localized to the nuclear speckles, but accumulated in cytoplasmic, perinuclear granule-like structures in cardiomyocytes, which might contribute to the more severe cardiac phenotypes.
Effects of long-lasting social isolation and re-socialization on cognitive performance and brain activity: a longitudinal study in Octodon degus
Authors: Rivera Daniela S. , Lindsay Carolina B. , Oliva Carolina A. , Codocedo Juan Francisco , Bozinovic Francisco , Inestrosa Nibaldo C.
Published: October 2020

Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function. Here, we investigated the effects of long-term social isolation on working memory, spatial learning/memory, hippocampal synaptic transmission, and synaptic proteins in the brain of adult female and male Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects, makes it a unique animal model that can be highly applicable for further social, emotional, cognitive, and aging studies. These animals were socially isolated from post-natal and post-weaning until adulthood. We also evaluated if re-socialization would be able to compensate for reactive stress responses in chronically stressed animals. We showed that long-term social isolation impaired the HPA axis negative feedback loop, which can be related to cognitive deficits observed in chronically stressed animals. Notably, re-socialization restored it. In addition, we measured physiological aspects of synaptic transmission, where chronically stressed males showed more efficient transmission but deficient plasticity, as the reverse was true on females. Finally, we analysed synaptic and canonical Wnt signalling proteins in the hypothalamus, hippocampus, and prefrontal cortex, finding both sex- and brain structure-dependent modulation, including transient and permanent changes dependent on stress treatment.
Experimental adaptation of dengue virus 1 to Aedes albopictus mosquitoes by in vivo selection
Authors: Bellone Rachel , Lequime Sebastian , Jupille Henri , Göertz Giel P. , Aubry Fabien , Mousson Laurence , Piorkowski Géraldine , Yen Pei-Shi , Gabiane Gaelle , Vazeille Marie , Sakuntabhai Anavaj , Pijlman Gorben P. , de Lamballerie Xavier , Lambrechts Louis , Failloux Anna-Bella
Published: October 2020

In most of the world, Dengue virus (DENV) is mainly transmitted by the mosquito Aedes aegypti while in Europe, Aedes albopictus is responsible for human DENV cases since 2010. Identifying mutations that make DENV more competent for transmission by Ae. albopictus will help to predict emergence of epidemic strains. Ten serial passages in vivo in Ae. albopictus led to select DENV-1 strains with greater infectivity for this vector in vivo and in cultured mosquito cells. These changes were mediated by multiple adaptive mutations in the virus genome, including a mutation at position 10,418 in the DENV 3′UTR within an RNA stem-loop structure involved in subgenomic flavivirus RNA production. Using reverse genetics, we showed that the 10,418 mutation alone does not confer a detectable increase in transmission efficiency in vivo. These results reveal the complex adaptive landscape of DENV transmission by mosquitoes and emphasize the role of epistasis in shaping evolutionary trajectories of DENV variants.
An in-silico layer-by-layer adsorption study of the interaction between Rebaudioside A and the T1R2 human sweet taste receptor: modelling and biosensing perspectives
Authors: Arodola Olayide A. , Kanchi Suvardhan , Hloma Phathisanani , Bisetty Krishna , Asiri Abdullah M. , Inamuddin
Published: October 2020

The human sweet taste receptor (T1R2) monomer—a member of the G-protein coupled receptor family that detects a wide variety of chemically and structurally diverse sweet tasting molecules, is known to pose a significant threat to human health. Protein that lack crystal structure is a challenge in structure-based protein design. This study focused on the interaction of the T1R2 monomer with rebaudioside A (Reb-A), a steviol glycoside with potential use as a natural sweetener using in-silico and biosensing methods. Herein, homology modelling, docking studies, and molecular dynamics simulations were applied to elucidate the interaction between Reb-A and the T1R2 monomer. In addition, the electrochemical sensing of the immobilised T1R2-Reb-A complex with zinc oxide nanoparticles (ZnONPs) and graphene oxide (GO) were assessed by testing the performance of multiwalled carbon nanotube (MWCNT) as an adsorbent experimentally. Results indicate a strong interaction between Reb-A and the T1R2 receptor, revealing the stabilizing interaction of the amino acids with the Reb-A by hydrogen bonds with the hydroxyl groups of the glucose moieties, along with a significant amount of hydrophobic interactions. Moreover, the presence of the MWCNT as an anchor confirms the adsorption strength of the T1R2-Reb-A complex onto the GO nanocomposite and supported with electrochemical measurements. Overall, this study could serve as a cornerstone in the development of electrochemical immunosensor for the detection of Reb-A, with applications in the food industry.
Potential energy of complex networks: a quantum mechanical perspective
Authors: Amoroso Nicola , Bellantuono Loredana , Pascazio Saverio , Lombardi Angela , Monaco Alfonso , Tangaro Sabina , Bellotti Roberto
Published: October 2020

We propose a characterization of complex networks, based on the potential of an associated Schrödinger equation. The potential is designed so that the energy spectrum of the Schrödinger equation coincides with the graph spectrum of the normalized Laplacian. Crucial information is retained in the reconstructed potential, which provides a compact representation of the properties of the network structure. The median potential over several random network realizations, which we call ensemble potential, is fitted via a Landau-like function, and its length scale is found to diverge as the critical connection probability is approached from above. The ruggedness of the ensemble potential profile is quantified by using the Higuchi fractal dimension, which displays a maximum at the critical connection probability. This demonstrates that this technique can be successfully employed in the study of random networks, as an alternative indicator of the percolation phase transition. We apply the proposed approach to the investigation of real-world networks describing infrastructures (US power grid). Curiously, although no notion of phase transition can be given for such networks, the fractality of the ensemble potential displays signatures of criticality. We also show that standard techniques (such as the scaling features of the largest connected component) do not detect any signature or remnant of criticality.
Magnetism and ion diffusion in honeycomb layered oxide $${\hbox {K}_2\hbox {Ni}_2\hbox {TeO}_6}$$
Authors: Matsubara Nami , Nocerino Elisabetta , Forslund Ola Kenji , Zubayer Anton , Papadopoulos Konstantinos , Andreica Daniel , Sugiyama Jun , Palm Rasmus , Guguchia Zurab , Cottrell Stephen P. , Kamiyama Takashi , Saito Takashi , Kalaboukhov Alexei , Sassa Yasmine , Masese Titus , Månsson Martin
Published: October 2020

In the quest for developing novel and efficient batteries, a great interest has been raised for sustainable K-based honeycomb layer oxide materials, both for their application in energy devices as well as for their fundamental material properties. A key issue in the realization of efficient batteries based on such compounds, is to understand the K-ion diffusion mechanism. However, investigation of potassium-ion (K$$^+$$

+

) dynamics in materials using e.g. NMR and related techniques has so far been very challenging, due to its inherently weak nuclear magnetic moment, in contrast to other alkali ions such as lithium and sodium. Spin-polarised muons, having a high gyromagnetic ratio, make the muon spin rotation and relaxation ($$\mu ^+$$

μ
+

SR) technique ideal for probing ions dynamics in these types of energy materials. Here we present a study of the low-temperature magnetic properties as well as K$$^+$$

+

dynamics in honeycomb layered oxide material $${\hbox {K}_2\hbox {Ni}_2\hbox {TeO}_6}$$

K
2

Ni
2

TeO
6

 using mainly the $$\mu ^+$$

μ
+

SR technique. Our low-temperature $$\mu ^+$$

μ
+

SR results together with complementary magnetic susceptibility measurements find an antiferromagnetic transition at $$T_{\mathrm{N}}\approx 27$$

T
N

≈
27

 K. Further $${\mu}^{+}$$

μ

+

SR studies performed at higher temperatures reveal that potassium ions (K$$^+$$

+

) become mobile above 200 K and the activation energy for the diffusion process is obtained as $$E_{\mathrm{a}}=121 (13)$$

E
a

=
121

(
13
)

 meV. This is the first time that K$$^+$$

+

dynamics in potassium-based battery materials has been measured using $$\mu ^+$$

μ
+

SR. Assisted by high-resolution neutron diffraction, the temperature dependence of the K-ion self diffusion constant is also extracted. Finally our results also reveal that K-ion diffusion occurs predominantly at the surface of the powder particles. This opens future possibilities for potentially improving ion diffusion as well as K-ion battery device performance using nano-structuring and surface coatings of the particles.
Lightweight design and static analysis of lattice compressor impeller
Authors: Zhang Yuan , Li Fanchun , Jia Dejun
Published: October 2020

Taking the compressor impeller as the research object and the lightweight design as the research goal, a lattice filled lattice cell suitable for the application of rotating periodic symmetric structure is designed. Its purpose is to make the rigidity and strength of impeller adjustable and reduce the mass of impeller on the premise of meeting the design requirements. The analysis and comparison of unfilled impeller, solid impeller and lattice filled impeller with different diameters were carried out under the limit condition of 80,000 r/min. The results showed that the average circumferential deformation of lattice impeller tip with beam diameter of 0.2 mm, 0.4 mm and 1 mm was 4.84%, 3.49% and 3.71% lower than that of solid impeller. For the impeller with a lattice beam diameter of 0.4 mm, its weight can be reduced by 22.68% compared with the solid impeller. The average circumferential deformation of the tip of the lattice impeller lies between the unfilled impeller and the solid impeller. The results show that the impeller with lattice filling hub can not only reduce the weight effectively, but also improve the efficiency of the compressor.
Observation of broad-band water waveguiding in shallow water: a revival
Authors: Sepúlveda-Soto Fabián , Guzmán-Silva Diego , Rosas Edgardo , Vicencio Rodrigo A. , Falcón Claudio
Published: October 2020

We report on the observation and characterization of broad-band waveguiding of surface gravity waves in an open channel, in the shallow water limit. The waveguide is constructed by changing locally the depth of the fluid layer, which creates conditions for surface waves to propagate along the generated guide. We present experimental and numerical results of this shallow water waveguiding, which can be straightforwardly matched to the one-dimensional water wave equation of shallow water waves. Our work revitalizes water waveguiding research as a relevant and controllable experimental setup to study complex phenomena using waveguide geometries.
Additive effect of atropine eye drops and short-term retinal defocus on choroidal thickness in children with myopia
Authors: Chiang Samuel T.-H. , Turnbull Philip R. K. , Phillips John R.
Published: October 2020

Atropine eye drops and myopic retinal defocus each slow progression of myopia (short-sight). They also cause thickening of the choroid, and it has been suggested that the thickening is a precursor for reduced eye growth and slowed myopia progression. We investigated whether choroidal thickening due to optical defocus would add to thickening due to atropine when both were applied simultaneously. Addition would suggest that combining the two clinical treatments may improve efficacy of myopia control. We studied 20 children receiving 0.3% atropine daily for myopia control, over a period of 6 months. We imposed short periods of retinal defocus (1 h of myopic or hyperopic defocus (± 2.00D)) both before, and after 1 week and 3 and 6 months of atropine treatment. Prior to atropine, myopic or hyperopic defocus caused significantly thicker or thinner choroids respectively (± 12 µm, p < 0.001). After one week of atropine alone, thickness had increased (+ 21 µm; SD 17 µm; p < 0.001), and it increased further (by + 13 µm; SD 6 µm; p < 0.001) when exposed to myopic defocus. Atropine abolished choroidal thinning in response to hyperopic defocus. These effects remained the same after 3 and 6 months of atropine treatment. Our results show that additive effects of atropine and optical defocus are present at the level of the choroid, and suggest that combining optical and pharmaceutical treatments is likely to enhance efficacy of clinical myopia control.
Superfluid density from magnetic penetration depth measurements in Nb–Cu 3D nano-composite films
Authors: Gupta Chandan , Parab Pradnya , Bose Sangita
Published: October 2020

Superconductivity in 3D Nb–Cu nanocomposite granular films have been studied with varying thickness for two different compositions, Nb rich with 88 at% of Nb and Cu rich with 46 at% of Nb. For both compositions, the superconducting transition temperature (Tc) decreases with decreasing film thickness. For any thickness, doubling the Cu content in the films decreases the Tc by about 2 K. To explore if phase fluctuations play any role in superconductivity in these 3D films, the superfluid stiffness (JS) of the films was measured using low frequency two-coil mutual inductance (M) technique. Interestingly, the measurement of M in magnetic fields showed two peaks in the imaginary component of M for both Nb rich and Cu rich films. The two peaks were associated with the pair-breaking effect of the magnetic field on the intra and inter-granular coupling in these films consisting of random network of superconductor (S) and normal metal (N) nano-particles. Furthermore, JS was seen to decrease with decreasing film thickness and increasing Cu content. However, for all films studied JS remained higher than the superconducting energy gap (∆) indicating that phase fluctuations do not play any role in superconductivity in the film thickness and composition range investigated. Our results indicate that an interplay of quantum size effects (QSE) and superconducting proximity effect (SPE) controls the Tc with composition in these 3D nano-composite films.
Fast kinetics of environmentally induced α-synuclein aggregation mediated by structural alteration in NAC region and result in structure dependent cytotoxicity
Authors: Srivastava Tulika , Raj Ritu , Dubey Amit , Kumar Dinesh , Chaturvedi Rajnish K. , Sharma Sandeep K. , Priya Smriti
Published: October 2020

Aggregation of α-synuclein (α-syn) is associated with the manifestation of various pathogenic synucleinopathies, including Parkinson’s disease attributed to both genetic and environmental stress factors. The initial events triggering α-syn aggregation and disease initiation due to environmental stress factors are still largely unknown. Here, to understand the mechanism of misfolding and aggregation initiation, we induced α-syn aggregation with rotenone, an established chemical inducer of PD like symptoms. We found that rotenone accelerates the formation of structurally distinct oligomers and fibrils that act as templates and increase the formation of conformers capable of spreading to the neighboring neuronal cells. Molecular dynamics simulations and NMR studies revealed the involvement of NAC region and formation of helical conformations resulting in structural variations in oligomers and fibrils. These structural variations affect the cytotoxic potential of oligomers and fibrils, where, the beta sheet rich oligomers and fibrils alter the membrane potential of neuronal cells and lead to early apoptosis. Our results describe the initial mechanistic events in pathogenic protein aggregation, where initial structural alterations in response to external stress factors dictate the toxicity of resulting conformers. This information will further provide insights in the understanding of protein aggregation, disease progression and pathogenesis.
Phosphorylation of Connexin36 near the C-terminus switches binding affinities for PDZ-domain and 14–3–3 proteins in vitro
Authors: Tetenborg Stephan , Wang Helen Y. , Nemitz Lena , Depping Anne , Espejo Alexsandra B. , Aseervatham Jaya , Bedford Mark T. , Janssen-Bienhold Ulrike , O’Brien John , Dedek Karin
Published: October 2020

Connexin36 (Cx36) is the most abundant connexin in central nervous system neurons. It forms gap junction channels that act as electrical synapses. Similar to chemical synapses, Cx36-containing gap junctions undergo activity-dependent plasticity and complex regulation. Cx36 gap junctions represent multimolecular complexes and contain cytoskeletal, regulatory and scaffolding proteins, which regulate channel conductance, assembly and turnover. The amino acid sequence of mammalian Cx36 harbors a phosphorylation site for the Ca2+/calmodulin-dependent kinase II at serine 315. This regulatory site is homologous to the serine 298 in perch Cx35 and in close vicinity to a PDZ binding domain at the very C-terminal end of the protein. We hypothesized that this phosphorylation site may serve as a molecular switch, influencing the affinity of the PDZ binding domain for its binding partners. Protein microarray and pulldown experiments revealed that this is indeed the case: phosphorylation of serine 298 decreased the binding affinity for MUPP1, a known scaffolding partner of connexin36, and increased the binding affinity for two different 14–3–3 proteins. Although we did not find the same effect in cell culture experiments, our data suggest that phosphorylation of serine 315/298 may serve to recruit different proteins to connexin36/35-containing gap junctions in an activity-dependent manner.
Identification of a juvenile-hormone signaling inhibitor via high-throughput screening of a chemical library
Authors: Kayukawa Takumi , Furuta Kenjiro , Nagamine Keisuke , Shinoda Tetsuro , Yonesu Kiyoaki , Okabe Takayoshi
Published: October 2020

Insecticide resistance has recently become a serious problem in the agricultural field. Development of insecticides with new mechanisms of action is essential to overcome this limitation. Juvenile hormone (JH) is an insect-specific hormone that plays key roles in maintaining the larval stage of insects. Hence, JH signaling pathway is considered a suitable target in the development of novel insecticides; however, only a few JH signaling inhibitors (JHSIs) have been reported, and no practical JHSIs have been developed. Here, we established a high-throughput screening (HTS) system for exploration of novel JHSIs using a Bombyx mori cell line (BmN_JF&AR cells) and carried out a large-scale screening in this cell line using a chemical library. The four-step HTS yielded 69 compounds as candidate JHSIs. Topical application of JHSI48 to B. mori larvae caused precocious metamorphosis. In ex vivo culture of the epidermis, JHSI48 suppressed the expression of the Krüppel homolog 1 gene, which is directly activated by JH-liganded receptor. Moreover, JHSI48 caused a parallel rightward shift in the JH response curve, suggesting that JHSI48 possesses a competitive antagonist-like activity. Thus, large-scale HTS using chemical libraries may have applications in development of future insecticides targeting the JH signaling pathway.
NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
Authors: Brandolini Laura , Antonosante Andrea , Giorgio Cristina , Bagnasco Michela , d’Angelo Michele , Castelli Vanessa , Benedetti Elisabetta , Cimini Annamaria , Allegretti Marcello
Published: October 2020

The progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Other studies allowed to clarify that the cardiovascular risk is not limited to COX-2 selective but also extended to non-selective NSAIDs, such as Diclofenac and Ketoprofen. To date, although a less favorable cardiovascular risk profile for Diclofenac as compared to Ketoprofen is reported, the mechanisms through which NSAIDs cause adverse cardiovascular events are not entirely understood. The present study aimed to evaluate the effects of Ketoprofen in comparison with Diclofenac in immortalized human cardiomyocytes. The results obtained highlight the dose-dependent cardiotoxicity of Diclofenac compared to Ketoprofen. Despite both drugs induce the increase in ROS production, decrease of mitochondrial membrane potential, and proteasome activity modulation, only Diclofenac exposure shows a marked alteration of these intracellular parameters, leading to cell death. Noteworthy, Diclofenac decreases the proteasome 26S DC and this scenario may be dependent on the intracellular overload of oxidized proteins. The data support the hypothesis that immortalized human cardiomyocytes exposed to Ketoprofen are subjected to tolerable stress events, conversely Diclofenac exposition triggers cell death.
pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery
Authors: Crawford Troy , Moshnikova Anna , Roles Sean , Weerakkody Dhammika , DuPont Michael , Carter Lukas M. , Shen John , Engelman Donald M. , Lewis Jason S. , Andreev Oleg A. , Reshetnyak Yana K.
Published: October 2020

Fluorescence imaging has seen enduring use in blood flow visualization and is now finding a new range of applications in image-guided surgery. In this paper, we report a translational study of a new fluorescent agent for use in surgery, pHLIP ICG, where ICG (indocyanine green) is a surgical fluorescent dye used widely for imaging blood flow. We studied pHLIP ICG interaction with the cell membrane lipid bilayer, the pharmacology and toxicology in vitro and in vivo (mice and dogs), and the biodistribution and clearance of pHLIP ICG in mice. The pHLIP ICG tumor targeting and imaging efficacy studies were carried out in several murine and human mouse tumor models. Blood vessels were imaged in mice and pigs. Clinical Stryker imaging instruments for endoscopy and open surgery were used in the study. Intravenously administered pHLIP ICG exhibits a multi-hour circulation half-life, offering protracted delineation of vasculature. As it clears from the blood, pHLIP ICG targets tumors and tumor stroma, marking them for surgical removal. pHLIP ICG is non-toxic, marks blood flow for hours after injection, and effectively delineates tumors for improved resection on the day after administration.
Identification of methionine -rich insoluble proteins in the shell of the pearl oyster, Pinctada fucata
Authors: Kintsu Hiroyuki , Nishimura Ryo , Negishi Lumi , Kuriyama Isao , Tsuchihashi Yasushi , Zhu Lingxiao , Nagata Koji , Suzuki Michio
Published: October 2020

The molluscan shell is a biomineral that comprises calcium carbonate and organic matrices controlling the crystal growth of calcium carbonate. The main components of organic matrices are insoluble chitin and proteins. Various kinds of proteins have been identified by solubilizing them with reagents, such as acid or detergent. However, insoluble proteins remained due to the formation of a solid complex with chitin. Herein, we identified these proteins from the nacreous layer, prismatic layer, and hinge ligament of Pinctada fucata using mercaptoethanol and trypsin. Most identified proteins contained a methionine-rich region in common. We focused on one of these proteins, NU-5, to examine the function in shell formation. Gene expression analysis of NU-5 showed that NU-5 was highly expressed in the mantle, and a knockdown of NU-5 prevented the formation of aragonite tablets in the nacre, which suggested that NU-5 was required for nacre formation. Dynamic light scattering and circular dichroism revealed that recombinant NU-5 had aggregation activity and changed its secondary structure in the presence of calcium ions. These findings suggest that insoluble proteins containing methionine-rich regions may be important for scaffold formation, which is an initial stage of biomineral formation.
Resolving the data asynchronicity in high-speed atomic force microscopy measurement via the Kalman Smoother
Authors: Kubo Shintaroh , Kato Suguru , Nakamura Kazuyuki , Kodera Noriyuki , Takada Shoji
Published: October 2020

High-speed atomic force microscopy (HS-AFM) is a scanning probe microscopy that can capture structural dynamics of biomolecules in real time at single molecule level near physiological condition. Albeit much improvement, while scanning one frame of HS-AFM movies, biomolecules often change their conformations largely. Thus, the obtained frame images can be hampered by the time-difference, the asynchronicity, in the data acquisition. Here, to resolve this data asynchronicity in the HS-AFM movie, we developed Kalman filter and smoother methods, some of the sequential Bayesian filtering approaches. The Kalman filter/smoother methods use alternative steps of a short time-propagation by a linear dynamical system and a correction by the likelihood of AFM data acquired pixel by pixel. We first tested the method using a toy model of a diffusing cone, showing that the Kalman smoother method outperforms to reproduce the ground-truth movie. We then applied the Kalman smoother to a synthetic movie for conformational change dynamics of a motor protein, i.e., dynein, confirming the superiority of the Kalman smoother. Finally, we applied the Kalman smoother to two real HS-AFM movies, FlhAC and centralspindlin, reducing distortion and noise in the AFM movies. The method is general and can be applied to any HS-AFM movies.
Biomechanical effects of original equipment manufacturer and aftermarket abutment screws in zirconia abutment on dental implant assembly
Authors: Wu Yu-Ling , Tsai Ming-Hsu , Chen Hung-Shyong , Chang Yu-Tsen , Lin Tsai-Te , Wu Aaron Yu-Jen
Published: October 2020

The use of aftermarket computer-aided design/computer-assisted manufacturing (CAD/CAM) prosthesis components in dental implants has become popular. This study aimed to (1) compare the accuracy of aftermarket CAD/CAM screws with that of original equipment manufacturer (OEM) abutment screws and (2) examine the biomechanical effects of different abutment screws used with zirconia abutment in an implant fixture by using three-dimensional finite element analysis (FEA). Significantly different measurements were obtained for the aftermarket CAD/CAM and OEM screws. The FEA results indicated that under the same loading condition, the maximum stress of the aftermarket CAD/CAM screws was 15.9% higher than that of the OEM screws. Moreover, the maximum stress position occurred in a wide section of the OEM screws but in the narrowest section of the aftermarket screws. The stress of the OEM zirconia abutment was 14.9% higher when using the aftermarket screws than when using the OEM screws. The effect of the manufacturing differences between aftermarket and OEM screws on the clinical effect of aftermarket screws is unpredictable. Therefore, aftermarket screws should be cautiously used clinically.
Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses
Authors: Hensel Janine , McAndrews Kathleen M. , McGrail Daniel J. , Dowlatshahi Dara P. , LeBleu Valerie S. , Kalluri Raghu
Published: October 2020

The Bacillus Calmette–Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is thought to provide protection against non-TB infectious diseases. BCG vaccination has recently been proposed as a strategy to prevent infection with SARS-CoV-2 (CoV-2) to combat the COVID-19 outbreak, supported by its potential to boost innate immunity and initial epidemiological analyses which observed reduced severity of COVID-19 in countries with universal BCG vaccination policies. Seventeen clinical trials are currently registered to inform on the benefits of BCG vaccinations upon exposure to CoV-2. Numerous epidemiological analyses showed a correlation between incidence of COVID-19 and BCG vaccination policies. These studies were not systematically corrected for confounding variables. We observed that after correction for confounding variables, most notably testing rates, there was no association between BCG vaccination policy and COVD-19 spread rate or percent mortality. Moreover, we found variables describing co-morbidities, including cardiovascular death rate and smoking prevalence, were significantly associated COVID-19 spread rate and percent mortality, respectively. While reporting biases may confound our observations, our epidemiological findings do not provide evidence to correlate overall BCG vaccination policy with the spread of CoV-2 and its associated mortality.
Analysis of streaming potential flow and electroviscous effect in a shear-driven charged slit microchannel
Authors: Riad Adham , Khorshidi Behnam , Sadrzadeh Mohtada
Published: October 2020

Investigating the flow behavior in microfluidic systems has become of interest due to the need for precise control of the mass and momentum transport in microfluidic devices. In multilayered-flows, precise control of the flow behavior requires a more thorough understanding as it depends on multiple parameters. The following paper proposes a microfluidic system consisting of an aqueous solution between a moving plate and a stationary wall, where the moving plate mimics a charged oil–water interface. Analytical expressions are derived by solving the nonlinear Poisson–Boltzmann equation along with the simplified Navier–Stokes equation to describe the electrokinetic effects on the shear-driven flow of the aqueous electrolyte solution. The Debye–Huckel approximation is not employed in the derivation extending its compatibility to high interfacial zeta potential. Additionally, a numerical model is developed to predict the streaming potential flow created due to the shear-driven motion of the charged upper wall along with its associated electric double layer effect. The model utilizes the extended Nernst–Planck equations instead of the linearized Poisson–Boltzmann equation to accurately predict the axial variation in ion concentration along the microchannel. Results show that the interfacial zeta potential of the moving interface greatly impacts the velocity profile of the flow and can reverse its overall direction. The numerical results are validated by the analytical expressions, where both models predicted that flow could reverse its overall direction when the interfacial zeta potential of the oil–water is above a certain threshold value. Finally, this paper describes the electroviscous effect as well as the transient development of electrokinetic effects within the microchannel.
A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs
Authors: Igase Masaya , Nemoto Yuki , Itamoto Kazuhito , Tani Kenji , Nakaichi Munekazu , Sakurai Masashi , Sakai Yusuke , Noguchi Shunsuke , Kato Masahiro , Tsukui Toshihiro , Mizuno Takuya
Published: October 2020

Inhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.
Development of a novel immune-related genes prognostic signature for osteosarcoma
Authors: Wu Zuo-long , Deng Ya-jun , Zhang Guang-zhi , Ren En-hui , Yuan Wen-hua , Xie Qi-qi
Published: October 2020

Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p < 0.05, p < 0.01), and clinical subgroup showed that the signature’s prognostic ability was independent of clinicopathological factors. Univariate and multivariate Cox regression analyses also supported its prognostic value. In conclusion, we developed an IRGs signature that is a prognostic indicator in OS patients, and the signature might serve as potential prognostic indicator to identify outcome of OS and facilitate personalized management of the high-risk patients.
Transferrin receptor 1 is a cellular receptor for human heme-albumin
Authors: Jennifer Brell , Berg Verena , Modak Madhura , Puck Alexander , Seyerl-Jiresch Maria , Künig Sarojinidevi , Zlabinger Gerhard J. , Steinberger Peter , Chou Janet , Geha Raif S. , Öhler Leopold , Yachie Akihiro , Choe Hyeryun , Kraller Markus , Stockinger Hannes , Stöckl Johannes
Published: October 2020

Iron is essential for living cells. Uptake of iron-loaded transferrin by the transferrin receptor 1 (CD71, TFR) is a major but not sufficient mechanism and an alternative iron-loaded ligand for CD71 has been assumed. Here, we demonstrate that CD71 utilizes heme-albumin as cargo to transport iron into human cells. Binding and endocytosis of heme-albumin via CD71 was sufficient to promote proliferation of various cell types in the absence of transferrin. Growth and differentiation of cells induced by heme-albumin was dependent on heme-oxygenase 1 (HO-1) function and was accompanied with an increase of the intracellular labile iron pool (LIP). Import of heme-albumin via CD71 was further found to contribute to the efficacy of albumin-based drugs such as the chemotherapeutic Abraxane. Thus, heme-albumin/CD71 interaction is a novel route to transport nutrients or drugs into cells and adds to the emerging function of CD71 as a scavenger receptor.
Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation
Authors: Wu Ping-Hsiu , Onodera Yasuhito , Giaccia Amato J. , Le Quynh-Thu , Shimizu Shinichi , Shirato Hiroki , Nam Jin-Min
Published: October 2020

Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression ofARL8Band BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis.
Coulomb drag transistor using a graphene and MoS2 heterostructure
Authors: Jin Youngjo , Joo Min-Kyu , Moon Byoung Hee , Kim Hyun , Lee Sanghyup , Jeong Hye Yun , Lee Young Hee
Published: October 2020

Two-dimensional (2D) heterostructures often provide extraordinary carrier transport as exemplified by superconductivity or excitonic superfluidity. Recently, a double-layer graphene (Gr) separated by few-layered boron nitride demonstrated the Coulomb drag phenomenon: carriers in the active layer drag carriers in the passive layer. Here, we propose high-performance Gr/MoS2 heterostructure transistors operating via Coulomb drag, exhibiting a high carrier mobility (∼3700 cm2 V−1 s−1) and on/off-current ratio (∼108) at room temperature. The van der Waals gap at the Gr/MoS2 interface induces strong interactions between the interlayer carriers, whose recombination is suppressed by the Schottky barrier between p-Gr and n-MoS2, clearly distinct from the presence of insulating layers. The sign reversal of lateral voltage clearly demonstrates the Coulomb drag in carrier transport. Hole-like behavior of electrons in the n-MoS2 is observed in magnetic field, indicating strong Coulomb drag at low temperature. Our Coulomb drag transistor thus provides a shortcut for the practical application of 2D heterostructures.
A ratiometric bilirubin sensor based on a fluorescent gold nanocluster film with dual emissions
Authors: Xiao Wenxiang , Zhi Dongcan , Pan Qiaoni , Liang Yongbo , Zhou Fang , Chen Zhencheng
Published: October 2020

Bilirubin originates from hemoglobin metabolism and is an important biomarker for liver function.
Transition metal-free and regioselective vinylation of phosphine oxides and H-phosphinates with VBX reagents
Authors: Castoldi Laura , Rajkiewicz Adam A. , Olofsson Berit
Published: October 2020

Vinylbenziodoxolones (VBX) were demonstrated as efficient, metal-free P-vinylation reagents with complete regioselectivity in favor of the terminal alkenes.
Rational design of [e]-fusion induced high-performance DHP/CPD based photoswitches
Authors: Han Li , Li Heming , Zuo Xi , Gao Quan , Li Dongmei , Cui Bin , Fang Changfeng , Liu Desheng
Published: October 2020

We report an effective strategy for improving the electronic transport and switching behaviors of DHP/CPD-based molecular devices, an intriguing photoswitch that can be triggered by ultraviolet/visible (UV-vis) light irradiation.
Rational design of the carbon doping of hexagonal boron nitride for oxygen activation and oxidative desulfurization
Authors: Li Hongping , Fu Wendi , Yin Jie , Zhang Jinrui , Li Yujun , Jiang Ding , Lv Naixia , Zhu Wenshuai
Published: October 2020

The doping of hexagonal boron nitride (h-BN) materials has a great influence on their catalytic oxidation performance, but the mechanism of doping has still not been studied in-depth to date.
Lowering the Schottky barrier height of G/WSSe van der Waals heterostructures by changing the interlayer coupling and applying external biaxial strain
Authors: Zhang W. X. , Yin Y. , He C.
Published: October 2020

Graphene-based van der Waals (vdW) heterostructures composed of two-dimensional transition metal dichalcogenides (TMDs) and graphene show great potential in the design and manufacture of field effect transistors.
Biological concepts for catalysis and reactivity: empowering bioinspiration
Authors: Das Agnideep , Hessin Cheriehan , Ren Yufeng , Desage-El Murr Marine
Published: October 2020

This review provides insights on how enzymatic reactivity tricks such as redox-active ligands, entatic state reactivity, electron bifurcation, and quantum tunneling can benefit chemists in the design of bioinspired catalytic systems.
Tailored activity of Cu–Fe bimetallic Beta zeolite with promising C3H6resistance for NH3-SCR
Authors: Zhao Qi , Chen Bingbing , Zou Bolin , Yu Limei , Shi Chuan
Published: October 2020

The introduction of Cu has inhibited the polymerization of C3H6and promoted the oxidation of C3H6, which alleviated competitive adsorption between C3H6and NOx, therefore results in the enhanced NH3-SCR performance in the presence of C3H6.
Recognizing soft templates as stimulators in multivariate modulation of tin phosphate and its application in catalysis for alkyl levulinate synthesis
Authors: Manjunathan Pandian , Shanbhag Dhanush Y. , Vinu Ajayan , Shanbhag Ganapati V.
Published: October 2020

Soft template tunes and controls explicitly both morphology and nature of active sites during the synthesis of tin phosphate catalyst. This synthesis strategy helped in producing alkyl levulinate in high yields from one-pot alcoholysis of furfuryl alcohol.
Chromium-catalysed efficient N-formylation of amines with a recyclable polyoxometalate-supported green catalyst
Authors: Dan Demin , Chen Fubo , Zhao Whenshu , Yu Han , Han Sheng , Wei Yongge
Published: October 2020

A simple and efficient protocol for the formylation of amines with formic acid, catalyzed by a polyoxometalate-based chromium catalyst, is described.