bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral efficacy of favipiravir against Zika and SARS-CoV-2 viruses in non-human primates
Authors: Marlin Romain , Desjardins Delphine , Contreras Vanessa , Lingas Guillaume , Solas Caroline , Roques Pierre , Naninck Thibaut , Pascal Quentin , Behillil Sylvie , Maisonnasse Pauline , Lemaitre Julien , Kahlaoui Nidhal , Delache Benoit , Pizzorno Andrés , Nougairede Antoine , Ludot Camille , Terrier Olivier , Dereuddre-Bosquet Nathalie , Relouzat Francis , Chapon Catherine , Ho Tsong Fang Raphael , van der Werf Sylvie , Rosa Calatrava Manuel , Malvy Denis , de Lamballerie Xavier , Guedj Jeremie , Le Grand Roger 
Published: August 2022

AbstractThe COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising in vitro results to successful clinical implementation. Among the drugs that have been largely tested in clinical trials but failed so far to bring clear evidence of clinical efficacy is favipiravir, a nucleoside analogue with large spectrum activity against several RNA viruses in vitro and in small animal models. Here, we evaluate the antiviral activity of favipiravir against Zika or SARS-CoV-2 virus in cynomolgus macaques. In both models, high doses of favipiravir are initiated before infection and viral kinetics are evaluated during 7 to 15 days after infection. Favipiravir leads to a statistically significant reduction in plasma Zika viral load compared to untreated animals. However, favipiravir has no effects on SARS-CoV-2 viral kinetics, and 4 treated animals have to be euthanized due to rapid clinical deterioration, suggesting a potential role of favipiravir in disease worsening in SARS-CoV-2 infected animals. To summarize, favipiravir has an antiviral activity against Zika virus but not against SARS-CoV-2 infection in the cynomolgus macaque model. Our results support the clinical evaluation of favipiravir against Zika virus but they advocate against its use against SARS-CoV-2 infection.
Dynamic mechanisms of CRISPR interference by Escherichia coli CRISPR-Cas3
Authors: Yoshimi Kazuto , Takeshita Kohei , Kodera Noriyuki , Shibumura Satomi , Yamauchi Yuko , Omatsu Mine , Umeda Kenichi , Kunihiro Yayoi , Yamamoto Masaki , Mashimo Tomoji 
Published: August 2022

AbstractType I CRISPR-Cas3 uses an RNA-guided multi Cas-protein complex, Cascade, which detects and degrades foreign nucleic acids via the helicase-nuclease Cas3 protein. Despite many studies using cryoEM and smFRET, the precise mechanism of Cas3-mediated cleavage and degradation of target DNA remains elusive. Here we reconstitute the CRISPR-Cas3 system in vitro to show how the Escherichia coli Cas3 (EcoCas3) with EcoCascade exhibits collateral non-specific single-stranded DNA (ssDNA) cleavage and target specific DNA degradation. Partial binding of EcoCascade to target DNA with tolerated mismatches within the spacer sequence, but not the PAM, elicits collateral ssDNA cleavage activity of recruited EcoCas3. Conversely, stable binding with complete R-loop formation drives EcoCas3 to nick the non-target strand (NTS) in the bound DNA. Helicase-dependent unwinding then combines with trans ssDNA cleavage of the target strand and repetitive cis cleavage of the NTS to degrade the target double-stranded DNA (dsDNA) substrate. High-speed atomic force microscopy demonstrates that EcoCas3 bound to EcoCascade repeatedly reels and releases the target DNA, followed by target fragmentation. Together, these results provide a revised model for collateral ssDNA cleavage and target dsDNA degradation by CRISPR-Cas3, furthering understanding of type I CRISPR priming and interference and informing future genome editing tools.
The supernova remnant SN 1006 as a Galactic particle accelerator
Authors: Giuffrida Roberta , Miceli Marco , Caprioli Damiano , Decourchelle Anne , Vink Jacco , Orlando Salvatore , Bocchino Fabrizio , Greco Emanuele , Peres Giovanni 
Published: August 2022

AbstractThe origin of cosmic rays is a pivotal open issue of high-energy astrophysics. Supernova remnants are strong candidates to be the Galactic factory of cosmic rays, their blast waves being powerful particle accelerators. However, supernova remnants can power the observed flux of cosmic rays only if they transfer a significant fraction of their kinetic energy to the accelerated particles, but conclusive evidence for such efficient acceleration is still lacking. In this scenario, the shock energy channeled to cosmic rays should induce a higher post-shock density than that predicted by standard shock conditions. Here we show this effect, and probe its dependence on the orientation of the ambient magnetic field, by analyzing deep X-ray observations of the Galactic remnant of SN 1006. By comparing our results with state-of-the-art models, we conclude that SN 1006 is an efficient source of cosmic rays and obtain an observational support for the quasi-parallel acceleration mechanism.
Structural bases for aspartate recognition and polymerization efficiency of cyanobacterial cyanophycin synthetase
Authors: Miyakawa Takuya , Yang Jian , Kawasaki Masato , Adachi Naruhiko , Fujii Ayumu , Miyauchi Yumiko , Muramatsu Tomonari , Moriya Toshio , Senda Toshiya , Tanokura Masaru 
Published: August 2022

AbstractCyanophycin is a natural biopolymer consisting of equimolar amounts of aspartate and arginine as the backbone and branched sidechain, respectively. It is produced by a single enzyme, cyanophycin synthetase (CphA1), and accumulates as a nitrogen reservoir during N2 fixation by most cyanobacteria. A recent structural study showed that three constituent domains of CphA1 function as two distinct catalytic sites and an oligomerization interface in cyanophycin synthesis. However, it remains unclear how the ATP-dependent addition of aspartate to cyanophycin is initiated at the catalytic site of the glutathione synthetase-like domain. Here, we report the cryogenic electron microscopy structures of CphA1, including a complex with aspartate, cyanophycin primer peptide, and ATP analog. These structures reveal the aspartate binding mode and phosphate-binding loop movement to the active site required for the reaction. Furthermore, structural and mutational data show a potential role of protein dynamics in the catalytic efficiency of the arginine condensation reaction.
Dysautonomia and REM sleep behavior disorder contributions to progression of Parkinson’s disease phenotypes
Authors: Riboldi Giulietta Maria , Russo Marco J. , Pan Ling , Watkins Kristen , Kang Un Jung 
Published: August 2022

AbstractNon-motor symptoms of Parkinson’s disease (PD) such as dysautonomia and REM sleep behavior disorder (RBD) are recognized to be important prodromal symptoms that may also indicate clinical subtypes of PD with different pathogenesis. Unbiased clustering analyses showed that subjects with dysautonomia and RBD symptoms, as well as early cognitive dysfunction, have faster progression of the disease. Through analysis of the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we tested the hypothesis that symptoms of dysautonomia and RBD, which are readily assessed by standard questionnaires in an ambulatory care setting, may help to independently prognosticate disease progression. Although these two symptoms associate closely, dysautonomia symptoms predict severe progression of motor and non-motor symptoms better than RBD symptoms across the 3-year follow-up period. Autonomic system involvement has not received as much attention and may be important to consider for stratification of subjects for clinical trials and for counseling patients.
Conveyor-mode single-electron shuttling in Si/SiGe for a scalable quantum computing architecture
Authors: Seidler Inga , Struck Tom , Xue Ran , Focke Niels , Trellenkamp Stefan , Bluhm Hendrik , Schreiber Lars R. 
Published: August 2022

AbstractSmall spin-qubit registers defined by single electrons confined in Si/SiGe quantum dots operate successfully and connecting these would permit scalable quantum computation. Shuttling the qubit carrying electrons between registers is a natural choice for high-fidelity coherent links provided the overhead of control signals stays moderate. Our proof-of-principle demonstrates shuttling of a single electron by a propagating wave-potential in an electrostatically defined 420 nm long Si/SiGe quantum-channel. This conveyor-mode shuttling approach requires independent from its length only four sinusoidal control signals. We discuss the tuning of the signal parameters, detect the smoothness of the electron motion enabling the mapping of potential disorder and observe a high single-electron shuttling fidelity of 99.42 ± 0.02% including a reversal of direction. Our shuttling device can be readily embedded in industrial fabrication of Si/SiGe qubit chips and paves the way to solving the signal-fanout problem for a fully scalable semiconductor quantum-computing architecture.
Silver nanoparticles synthesized from the seaweed Sargassum polycystum and screening for their biological potential
Authors: Thiurunavukkarau Rajasekar , Shanmugam Sabarika , Subramanian Kumaran , Pandi Priyadarshini , Muralitharan Gangatharan , Arokiarajan Maryshamya , Kasinathan Karthika , Sivaraj Anbarasu , Kalyanasundaram Revathy , AlOmar Suliman Yousef , Shanmugam Velmurugan 
Published: August 2022

AbstractWorld-wide antimicrobial resistant is biggest threat in global health. It requires the urgent need of multisectoral action for the scientific community to achieve the sustainable development Goals. Due to their antimicrobial properties, silver nanoparticles are potential activates to pathogens, which explains their potential for multiple applications in various fields. In the present studies, we evaluate the antimicrobial properties of a Sargassum polycystum algal extract, an unrivaled green synthetic method for producing -defined shaped seaweed silver nanoparticles. To confirm their structure and size, some characterization techniques are used, such as Absorption spectrophotometer (UV–VIS), Fourier transforms infrared spectroscopy (FTIR), Scanning electron Microscope (SEM), Transmission electron microscopy (TEM) and X-Ray diffraction (XRD). Evaluate the antibacterial and anti-mycobacterial activity using silver nanoparticles. The toxicity study of this silver nanoparticle has been done with the help of zebrafish larva. The biological nanoparticle having good antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, Pseudomonas fluorescens and Candida albicans and also it shows potent activity against MTB H37Rv, SHRE sensitive MTB Rifampicin resistant MTB around 98%. Seaweed nanoparticles had lower toxicity for the survival of the fish larvae. In comparison, other dosages will arrest the cell cycle and leads to death. The present finding revealed that these seaweeds nanoparticles have potential anti-mycobacterial activity against pathogens at low concentrations. This makes them a potent source of antibacterial and anti-TB agents
Comparison between bearing strengths of molded-in and machined holes of GFR/PP composites
Authors: Osama M. M. , Selmy A. I. , Abdelhaleem Ayman M. M. , Megahed A. A. 
Published: August 2022

AbstractThis study is an investigation of weight fraction (wt%) and fiber feedstock length (FFSL) effects on the bearing strength (BS) of bolted joints in glass-fiber-reinforced (GFR) polypropylene (PP) composites manufactured by an injection molding technique. The investigation was made for holes produced either by molding or machining. For machined holes, the effect of drilling parameters (feed and speed) on BS was discussed. It is observed that BS decreased as FFSL increased. BS of both molded-in and drilled specimens was enhanced by increasing wt% of glass fiber. While slightly better BS was observed for molded-in specimens than drilled ones for all specimens. The drilling conditions’ effect on BS was found to be insignificant for drilled holes in long fibers reinforced PP, where the most significant factor was wt%. However, for short fibers reinforced PP, the spindle speed was the most significant factor followed by feed, while wt% has the lowest effect. Failure morphology mode for specimens indicates that for molded-in specimens, neat PP specimens failed under pure bearing mode while GFR/PP specimens failed under the mixed-mode failure (bearing and net tension). For machined specimens, all specimens failed under mixed-mode failure except for the highest wt% specimens which failed under net tension.
Changes in cross-sectional areas of posterior extensor muscles in thoracic spine: a 10-year longitudinal MRI study
Authors: Umezawa Hitoshi , Daimon Kenshi , Fujiwara Hirokazu , Nishiwaki Yuji , Michikawa Takehiro , Okada Eijiro , Nojiri Kenya , Watanabe Masahiko , Katoh Hiroyuki , Shimizu Kentaro , Ishihama Hiroko , Fujita Nobuyuki , Tsuji Takashi , Nakamura Masaya , Matsumoto Morio , Watanabe Kota 
Published: August 2022

AbstractAge-related changes in the posterior extensor muscles of the cervical and lumbar spine have been reported in some studies; however, longitudinal changes in the thoracic spine of healthy subjects are rarely reported. Therefore, this study aimed to evaluate changes in the cross-sectional areas (CSAs) of posterior extensor muscles in the thoracic spine over 10 years and identify related factors. The subjects of this study were 85 volunteers (mean age: 44.7 ± 11.5) and the average follow-up period was about 10 years. The CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles from T1/2 to T11/12 were measured on magnetic resonance imaging. The extent of muscle fat infiltration was assessed by the signal intensity (luminance) of the extensor muscles’ total cross-section compared to a section of pure muscle. We applied a Poisson regression model, which is included in the generalized linear model, and first examined the univariate (crude) association between each relevant factor (age, sex, body mass index, lifestyle, back pain, neck pain, neck stiffness, and intervertebral disc degeneration) and CSA changes. Then, we constructed a multivariate model, which included age, sex, and related factors in the univariate analysis. The mean CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles significantly increased over 10 years. Exercise habit was associated with increased CSAs of the erector spinae muscles and the total area of the extensor muscles. The cross-section mean luminance significantly increased from baseline, indicating a significant increase of fat infiltration in the posterior extensor muscles. Progression of disc degeneration was inversely associated with increased fat infiltration in the total extensor muscles.
The utility of texture analysis of kidney MRI for evaluating renal dysfunction with multiclass classification model
Authors: Hara Yuki , Nagawa Keita , Yamamoto Yuya , Inoue Kaiji , Funakoshi Kazuto , Inoue Tsutomu , Okada Hirokazu , Ishikawa Masahiro , Kobayashi Naoki , Kozawa Eito 
Published: August 2022

AbstractWe evaluated a multiclass classification model to predict estimated glomerular filtration rate (eGFR) groups in chronic kidney disease (CKD) patients using magnetic resonance imaging (MRI) texture analysis (TA). We identified 166 CKD patients who underwent MRI comprising Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) images, apparent diffusion coefficient (ADC) maps, and T2* maps. The patients were divided into severe, moderate, and control groups based on eGFR borderlines of 30 and 60 mL/min/1.73 m2. After extracting 93 texture features (TFs), dimension reduction was performed using inter-observer reproducibility analysis and sequential feature selection (SFS) algorithm. Models were created using linear discriminant analysis (LDA); support vector machine (SVM) with linear, rbf, and sigmoid kernels; decision tree (DT); and random forest (RF) classifiers, with synthetic minority oversampling technique (SMOTE). Models underwent 100-time repeat nested cross-validation. Overall performances of our classification models were modest, and TA based on T1-weighted IP/OP/WO images provided better performance than those based on ADC and T2* maps. The most favorable result was observed in the T1-weighted WO image using RF classifier and the combination model was derived from all T1-weighted images using SVM classifier with rbf kernel. Among the selected TFs, total energy and energy had weak correlations with eGFR.
Fat3 regulates neural progenitor cells by promoting Yap activity during spinal cord development
Authors: Seo Soyeon , Kim Young A. , Lee Junekyoung , Lee Seunghwan , Kim Jumee , Lee Seunghee 
Published: August 2022

AbstractEarly embryonic development of the spinal cord requires tight coordination between proliferation of neural progenitors and their differentiation into distinct neuronal cell types to establish intricate neuronal circuits. The Hippo pathway is one of the well-known regulators to control cell proliferation and govern neural progenitor cell number, in which the downstream effector Yes-associated protein (Yap) promotes cell cycle progression. Here we show that an atypical cadherin Fat3, expressed highly in the neural tube, plays a critical role in maintaining proper number of proliferating progenitors. Knockdown of Fat3 in chick neural tube down-regulates expression of the proliferation markers but rather induces the expression of neural markers in the ventricular zone. We further show that deletion of Fat3 gene in mouse neural tube depletes neural progenitors, accompanied by neuronal gene expression in the ventral ventricular zone of the spinal cord. Finally, we found that Fat3 regulates the phosphorylation level of Lats1/2, the upstream kinase of Yap, resulting in dephosphorylation and stabilization of Yap, suggesting Yap as a key downstream effector of Fat3. Our study uncovers another layer of regulatory mechanisms in controlling the activity of Hippo signaling pathway to regulate the size of neural progenitor pools in the developing spinal cord.
Circ_0047339 promotes the activation of fibroblasts and affects the development of urethral stricture by targeting the miR-4691-5p/TSP-1 axis
Authors: Ding Ke , Li Daoyuan , Zhang Rui , Zuo Meilin 
Published: August 2022

AbstractUrethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM–receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA–miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.
Large emergent optoelectronic enhancement in molecularly cross-linked gold nanoparticle nanosheets
Authors: Gravelsins Steven , Park Myung Jin , Niewczas Marek , Hyeong Seok-Ki , Lee Seoung-Ki , Ahmed Aftab , Dhirani Al-Amin 
Published: August 2022

AbstractA central goal in molecular electronics and optoelectronics is to translate tailorable molecular properties to larger materials and to the device level. Here, we present a method to fabricate molecularly cross-linked, self-assembled 2D nanoparticle sheets (X-NS). Our method extends a Langmuir approach of self-assembling gold nanoparticle (NP) arrays at an air-water interface by replacing the liquid sub-phase to an organic solvent to enable cross-linking with organic molecules, and then draining the sub-phase to deposit films. Remarkably, X-NS comprising conjugated oligophenylene dithiol cross-linkers (HS-(C6H4)n-SH, 1 ≤ n ≤ 3) exhibit increasing conductance with molecule length, ~6 orders of magnitude enhancement in UV-Vis extinction coefficients, and photoconductivity with molecule vs. NP contributions varying depending on the excitation wavelength. Finite difference time domain (FDTD) analyses and control measurements indicate that these effects can be modeled provided the local complex dielectric constant is strongly modified upon cross-linking. This suggests quantum hybridization at a molecule–band (q-MB) level. Given the vast number of molecules and nano-building blocks available, X-NS have potential to significantly increase the range of available 2D nanosheets and associated quantum properties.
Reactive sulfur species and their significance in health and disease
Authors: Iciek Małgorzata , Bilska-Wilkosz Anna , Kozdrowicki Michał , Górny Magdalena 
Published: August 2022

Abstract
Reactive sulfur species (RSS) have been recognized in the last two decades as very important molecules in redox regulation. They are involved in metabolic processes and, in this way, they are responsible for maintenance of health. This review summarizes current information about the essential biological RSS, including H2S, low molecular weight persulfides, protein persulfides as well as organic and inorganic polysulfides, their synthesis, catabolism and chemical reactivity. Moreover, the role of RSS disturbances in various pathologies including vascular diseases, chronic kidney diseases, diabetes mellitus Type 2, neurological diseases, obesity, chronic obstructive pulmonary disease and in the most current problem of COVID-19 is presented. The significance of RSS in aging is also mentioned. Finally, the possibilities of using the precursors of various forms of RSS for therapeutic purposes are discussed.