bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma
Authors: Magill Stephen T. , Vasudevan Harish N. , Seo Kyounghee , Villanueva-Meyer Javier E. , Choudhury Abrar , John Liu S. , Pekmezci Melike , Findakly Sarah , Hilz Stephanie , Lastella Sydney , Demaree Benjamin , Braunstein Steve E. , Bush Nancy Ann Oberheim , Aghi Manish K. , Theodosopoulos Philip V. , Sneed Penny K. , Abate Adam R. , Berger Mitchel S. , McDermott Michael W. , Lim Daniel A. , Ullian Erik M. , Costello Joseph F. , Raleigh David R.
Published: September 2020

Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology.
T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration
Authors: Garbett Damien , Bisaria Anjali , Yang Changsong , McCarthy Dannielle G. , Hayer Arnold , Moerner W. E. , Svitkina Tatyana M. , Meyer Tobias
Published: September 2020

Migrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.
Particle engineering enabled by polyphenol-mediated supramolecular networks
Authors: Zhou Jiajing , Lin Zhixing , Penna Matthew , Pan Shuaijun , Ju Yi , Li Shiyao , Han Yiyuan , Chen Jingqu , Lin Gan , Richardson Joseph J. , Yarovsky Irene , Caruso Frank
Published: September 2020

We report a facile strategy for engineering diverse particles based on the supramolecular assembly of natural polyphenols and a self-polymerizable aromatic dithiol. In aqueous conditions, uniform and size-tunable supramolecular particles are assembled through π–π interactions as mediated by polyphenols. Owing to the high binding affinity of phenolic motifs present at the surface, these particles allow for the subsequent deposition of various materials (i.e., organic, inorganic, and hybrid components), producing a variety of monodisperse functional particles. Moreover, the solvent-dependent disassembly of the supramolecular networks enables their removal, generating a wide range of corresponding hollow structures including capsules and yolk–shell structures. The versatility of these supramolecular networks, combined with their negligible cytotoxicity provides a pathway for the rational design of a range of particle systems (including core–shell, hollow, and yolk–shell) with potential in biomedical and environmental applications.
REM sleep promotes experience-dependent dendritic spine elimination in the mouse cortex
Authors: Zhou Yanmei , Lai Cora Sau Wan , Bai Yang , Li Wei , Zhao Ruohe , Yang Guang , Frank Marcos G. , Gan Wen-Biao
Published: September 2020

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction.
Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR
Authors: Smyrlaki Ioanna , Ekman Martin , Lentini Antonio , Rufino de Sousa Nuno , Papanicolaou Natali , Vondracek Martin , Aarum Johan , Safari Hamzah , Muradrasoli Shaman , Rothfuchs Antonio Gigliotti , Albert Jan , Högberg Björn , Reinius Björn
Published: September 2020

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is commonly diagnosed by reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA in patient samples, but RNA extraction constitutes a major bottleneck in current testing. Methodological simplification could increase diagnostic availability and efficiency, benefitting patient care and infection control. Here, we describe methods circumventing RNA extraction in COVID-19 testing by performing RT-PCR directly on heat-inactivated or lysed samples. Our data, including benchmarking using 597 clinical patient samples and a standardised diagnostic system, demonstrate that direct RT-PCR is viable option to extraction-based tests. Using controlled amounts of active SARS-CoV-2, we confirm effectiveness of heat inactivation by plaque assay and evaluate various generic buffers as transport medium for direct RT-PCR. Significant savings in time and cost are achieved through RNA-extraction-free protocols that are directly compatible with established PCR-based testing pipelines. This could aid expansion of COVID-19 testing.
Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility
Authors: Harding Clare R. , Sidik Saima M. , Petrova Boryana , Gnädig Nina F. , Okombo John , Herneisen Alice L. , Ward Kurt E. , Markus Benedikt M. , Boydston Elizabeth A. , Fidock David A. , Lourido Sebastian
Published: September 2020

Artemisinins have revolutionized the treatment of Plasmodium falciparum malaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations. Using a sublethal concentration of dihydroartemisinin (DHA), we uncover the putative transporter Tmem14c whose disruption increases DHA susceptibility. Screens performed under high doses of DHA provide evidence that mitochondrial metabolism can modulate resistance. We show that disrupting a top candidate from the screens, the mitochondrial protease DegP2, lowers porphyrin levels and decreases DHA susceptibility, without significantly altering parasite fitness in culture. Deleting the homologous gene in P. falciparum, PfDegP, similarly lowers heme levels and DHA susceptibility. These results expose the vulnerability of heme metabolism to genetic perturbations that can lead to increased survival in the presence of DHA.
Orthogonal colloidal quantum dot inks enable efficient multilayer optoelectronic devices
Authors: Lee Seungjin , Choi Min-Jae , Sharma Geetu , Biondi Margherita , Chen Bin , Baek Se-Woong , Najarian Amin Morteza , Vafaie Maral , Wicks Joshua , Sagar Laxmi Kishore , Hoogland Sjoerd , de Arquer F. Pelayo García , Voznyy Oleksandr , Sargent Edward H.
Published: September 2020

Surface ligands enable control over the dispersibility of colloidal quantum dots (CQDs) via steric and electrostatic stabilization. Today’s device-grade CQD inks have consistently relied on highly polar solvents: this enables facile single-step deposition of multi-hundred-nanometer-thick CQD films; but it prevents the realization of CQD film stacks made up of CQDs having different compositions, since polar solvents redisperse underlying films. Here we introduce aromatic ligands to achieve process-orthogonal CQD inks, and enable thereby multifunctional multilayer CQD solids. We explore the effect of the anchoring group of the aromatic ligand on the solubility of CQD inks in weakly-polar solvents, and find that a judicious selection of the anchoring group induces a dipole that provides additional CQD-solvent interactions. This enables colloidal stability without relying on bulky insulating ligands. We showcase the benefit of this ink as the hole transport layer in CQD optoelectronics, achieving an external quantum efficiency of 84% at 1210 nm.
Author Correction: RNAi mediated myosuppressin deficiency affects muscle development and survival in the salmon louse (Lepeophtheirus salmonis)
Authors: Komisarczuk Anna Z. , Kongshaug Heidi , Li Ming , Nilsen Frank
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Unraveling the effects of the gut microbiota composition and function on horse endurance physiology
Authors: Plancade Sandra , Clark Allison , Philippe Catherine , Helbling Jean-Christophe , Moisan Marie-Pierre , Esquerré Diane , Le Moyec Laurence , Robert Céline , Barrey Eric , Mach Núria
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: In vitro biological screening of a critically endangered medicinal plant, Atropa acuminata Royle Ex Lindl of north western Himalaya
Authors: Rahman Khaista , Khan Shahid Ullah , Fahad Shah , Shinwari Zabta Khan , Khan Dilfaraz , Kamal Sajid , Ullah Ikram , Anjum Syed Ishtiaq , Man Shad , Khan Abdul Jamil , Khan Wasim Ullah , Khan Muhammad Hafeez Ullah , Jan Mehmood , Adnan Muhammad , Noor Muhammad
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Extracting backbones in weighted modular complex networks
Authors: Ghalmane Zakariya , Cherifi Chantal , Cherifi Hocine , El Hassouni Mohammed
Published: September 2020

Network science provides effective tools to model and analyze complex systems. However, the increasing size of real-world networks becomes a major hurdle in order to understand their structure and topological features. Therefore, mapping the original network into a smaller one while preserving its information is an important issue. Extracting the so-called backbone of a network is a very challenging problem that is generally handled either by coarse-graining or filter-based methods. Coarse-graining methods reduce the network size by grouping similar nodes, while filter-based methods prune the network by discarding nodes or edges based on a statistical property. In this paper, we propose and investigate two filter-based methods exploiting the overlapping community structure in order to extract the backbone in weighted networks. Indeed, highly connected nodes (hubs) and overlapping nodes are at the heart of the network. In the first method, called “overlapping nodes ego backbone”, the backbone is formed simply from the set of overlapping nodes and their neighbors. In the second method, called “overlapping nodes and hubs backbone”, the backbone is formed from the set of overlapping nodes and the hubs. For both methods, the links with the lowest weights are removed from the network as long as a backbone with a single connected component is preserved. Experiments have been performed on real-world weighted networks originating from various domains (social, co-appearance, collaboration, biological, and technological) and different sizes. Results show that both backbone extraction methods are quite similar. Furthermore, comparison with the most influential alternative filtering method demonstrates the greater ability of the proposed backbones extraction methods to uncover the most relevant parts of the network.
Biodistribution of 131I in mice is influenced by circadian variations
Authors: Andersson Charlotte K. , Elvborn Mikael , Spetz Johan K. E. , Langen Britta , Forssell-Aronsson Eva B.
Published: September 2020

Effects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of 131I injection affects the biodistribution and absorbed dose to tissues in mice. Biodistribution studies were conducted on male C57BL/6 N mice for three diurnal time-series: the animals were i.v. injected with 160 kBq 131I at 8 am, 12 pm or 4 pm. The activity concentration in organs and tissues was measured at 1 h to 7 days after administration and absorbed dose at day 7 was determined. Comparison between the three time-series showed statistically significant differences in activity concentration in all investigated tissues and organs. Administration performed at 12 pm resulted in general in higher absorbed dose to the organs than injection performed at 8 am and 4 pm. Time of day of administration affects the biodistribution of 131I in mice and consequently the absorbed dose to individual organs. These findings advocate that subsequent biodistribution studies and dosimetry calculations should consider time-point of administration as a variable that could influence the results.
Modulation of CYP2C9 activity and hydrogen peroxide production by cytochrome b5
Authors: Gómez-Tabales Javier , García-Martín Elena , Agúndez José A. G. , Gutierrez-Merino Carlos
Published: September 2020

Cytochromes P450 (CYP) play a major role in drug detoxification, and cytochrome b5 (cyt b5) stimulates the catalytic cycle of mono-oxygenation and detoxification reactions. Collateral reactions of this catalytic cycle can lead to a significant production of toxic reactive oxygen species (ROS). One of the most abundant CYP isoforms in the human liver is CYP2C9, which catalyzes the metabolic degradation of several drugs including nonsteroidal anti-inflammatory drugs. We studied modulation by microsomal membrane-bound and soluble cyt b5 of the hydroxylation of salicylic acid to gentisic acid and ROS release by CYP2C9 activity in human liver microsomes (HLMs) and by CYP2C9 baculosomes. CYP2C9 accounts for nearly 75% of salicylic acid hydroxylation in HLMs at concentrations reached after usual aspirin doses. The anti-cyt b5 antibody SC9513 largely inhibits the rate of salicylic acid hydroxylation by CYP2C9 in HLMs and CYP2C9 baculosomes, increasing the KM approximately threefold. Besides, soluble human recombinant cyt b5 stimulates the Vmax nearly twofold while it decreases nearly threefold the Km value in CYP2C9 baculosomes. Regarding NADPH-dependent ROS production, soluble recombinant cyt b5 is a potent inhibitor both in HLMs and in CYP2C9 baculosomes, with inhibition constants of 1.04 ± 0.25 and 0.53 ± 0.06 µM cyt b5, respectively. This study indicates that variability in cyt b5 might be a major factor underlying interindividual variability in the metabolism of CYP2C9 substrates.
Physiologic blood flow is turbulent
Authors: Saqr Khalid M. , Tupin Simon , Rashad Sherif , Endo Toshiki , Niizuma Kuniyasu , Tominaga Teiji , Ohta Makoto
Published: September 2020

Contemporary paradigm of peripheral and intracranial vascular hemodynamics considers physiologic blood flow to be laminar. Transition to turbulence is considered as a driving factor for numerous diseases such as atherosclerosis, stenosis and aneurysm. Recently, turbulent flow patterns were detected in intracranial aneurysm at Reynolds number below 400 both in vitro and in silico. Blood flow is multiharmonic with considerable frequency spectra and its transition to turbulence cannot be characterized by the current transition theory of monoharmonic pulsatile flow. Thus, we decided to explore the origins of such long-standing assumption of physiologic blood flow laminarity. Here, we hypothesize that the inherited dynamics of blood flow in main arteries dictate the existence of turbulence in physiologic conditions. To illustrate our hypothesis, we have used methods and tools from chaos theory, hydrodynamic stability theory and fluid dynamics to explore the existence of turbulence in physiologic blood flow. Our investigation shows that blood flow, both as described by the Navier–Stokes equation and in vivo, exhibits three major characteristics of turbulence. Womersley’s exact solution of the Navier–Stokes equation has been used with the flow waveforms from HaeMod database, to offer reproducible evidence for our findings, as well as evidence from Doppler ultrasound measurements from healthy volunteers who are some of the authors. We evidently show that physiologic blood flow is: (1) sensitive to initial conditions, (2) in global hydrodynamic instability and (3) undergoes kinetic energy cascade of non-Kolmogorov type. We propose a novel modification of the theory of vascular hemodynamics that calls for rethinking the hemodynamic–biologic links that govern physiologic and pathologic processes.
Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity
Authors: Hung Chia-Chun , Liu Yi-Hsuan , Huang Chu-Chung , Chou Cheng-Ying , Chen Chun-Ming , Duann Jeng-Ren , Li Chiang-Shan R. , Lee Tony Szu-Hsien , Lin Ching-Po
Published: September 2020

Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.
Effect of cholecalciferol on serum hepcidin and parameters of anaemia and CKD-MBD among haemodialysis patients: a randomized clinical trial
Authors: Obi Yoshitsugu , Yamaguchi Satoshi , Hamano Takayuki , Sakaguchi Yusuke , Shimomura Akihiro , Namba-Hamano Tomoko , Mikami Satoshi , Nishi Osamu , Tanaka Motoko , Kamoto Akihito , Obi Yasue , Tomosugi Naohisa , Tsubakihara Yoshiharu , Isaka Yoshitaka
Published: September 2020

In this multicentre double-blind randomized clinical trial, we investigated the effects of oral cholecalciferol supplementation on serum hepcidin and parameters related to anaemia and CKD-MBD among haemodialysis patients. Participants were assigned in a 2:2:1:1 ratio to either (1) thrice-weekly 3,000-IU cholecalciferol, (2) once-monthly cholecalciferol (equivalent to 9,000 IU/week), (3) thrice-weekly placebo, or (4) once-monthly placebo. We also examined the effect modifications by selected single nucleotide polymorphisms in vitamin D-related genes. Out of 96 participants, 94 were available at Month 3, and 88 completed the 6-month study. After adjustment for baseline values, serum hepcidin levels were higher at Day 3 in the combined cholecalciferol (vs. placebo) group, but were lower at Month 6 with increased erythropoietin resistance. Cholecalciferol increased serum 1,25(OH)2D levels, resulting in a greater proportion of patients who reduced the dose of active vitamin D at Month 6 (31% vs. 10% in the placebo group). Cholecalciferol also suppressed intact PTH only among patients with severe vitamin D deficiency. In conclusion, cholecalciferol supplementation increases serum hepcidin-25 levels in the short term and may increase erythropoietin resistance in the long term among haemodialysis patients. Both thrice-weekly and once-monthly supplementation effectively increases serum 1,25(OH)2D levels, and hence, reduces active vitamin D drugs.

Clinical Trial Registry: This study was registered at ClinicalTrials.gov and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as NCT02214563 (registration date: 12/08/2014) and UMIN000011786 (registration date: 15/08/2014), respectively (please refer to the links below). ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/record/NCT02214563. UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000017152&language=E.
Evolution of outcome and complications in TAVR: a meta-analysis of observational and randomized studies
Authors: Winter Max-Paul , Bartko Philipp , Hofer Felix , Zbiral Martin , Burger Achim , Ghanim Bahil , Kastner Johannes , Lang Irene M. , Mascherbauer Julia , Hengstenberg Christian , Goliasch Georg
Published: September 2020

Aim of the present analysis was to collect and pool all available data currently in the literature regarding outcomes and complications of all approved TAVR prosthesis and to assess the transition from first to next generation TAVR devices by directly comparing both in regard of procedure related complications. Transcatheter aortic valve replacement is a well established treatment modality in patients with severe aortic stenosis deemed to be inoperable or at unacceptable risk for open heart surgery. First generation prostheses were associated with a high rate of peri-procedural complications like paravalvular regurgitation, valve malpositioning, vascular complications and conduction disorders. Refinement of the available devices incorporate features to address the limitations of the first-generation devices. A PRISMA checklist-guided systematic review and meta-analysis of prospective observational studies, national and device specific registries or randomized clinical trials was conducted. Studies were identified by searching PUBMED, SCOPUS, Cochrane Central Register of Controlled Trials and LILACs from January 2000 to October 2017. We extracted and pooled data on both mortality and complications from 273 studies for twelve different valves prostheses in a total of 68,193 patients. In second generation prostheses as compared to first generation devices, we observed a significant decrease in mortality (1.47 ± 1.73% vs. 5.41 ± 4.35%; p < 0.001), paravalvular regurgitation (1.75 ± 2.43vs. 12.39 ± 9.38, p < 0.001) and MACE. TAVR with contemporary next generation devices has led to an impressive improvement in TAVR safety driven by refined case selection, improved procedural techniques and increased site experience.
Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression
Authors: Seruggia Davide , Fernández Almudena , Cantero Marta , Fernández-Miñán Ana , Gomez-Skarmeta José Luis , Pelczar Pawel , Montoliu Lluis
Published: September 2020

Control of gene expression is dictated by cell-type specific regulatory sequences that physically organize the structure of chromatin, including promoters, enhancers and insulators. While promoters and enhancers convey cell-type specific activating signals, insulators prevent the cross-talk of regulatory elements within adjacent loci and safeguard the specificity of action of promoters and enhancers towards their targets in a tissue specific manner. Using the mouse tyrosinase (Tyr) locus as an experimental model, a gene whose mutations are associated with albinism, we described the chromatin structure in cells at two distinct transcriptional states. Guided by chromatin structure, through the use of Chromosome Conformation Capture (3C), we identified sequences at the 5′ and 3′ boundaries of this mammalian gene that function as enhancers and insulators. By CRISPR/Cas9-mediated chromosomal deletion, we dissected the functions of these two regulatory elements in vivo in the mouse, at the endogenous chromosomal context, and proved their mechanistic role as genomic insulators, shielding the Tyr locus from the expression patterns of adjacent genes.
Second wave COVID-19 pandemics in Europe: a temporal playbook
Authors: Cacciapaglia Giacomo , Cot Corentin , Sannino Francesco
Published: September 2020

A second wave pandemic constitutes an imminent threat to society, with a potentially immense toll in terms of human lives and a devastating economic impact. We employ the epidemic Renormalisation Group (eRG) approach to pandemics, together with the first wave data for COVID-19, to efficiently simulate the dynamics of disease transmission and spreading across different European countries. The framework allows us to model, not only inter and extra European border control effects, but also the impact of social distancing for each country. We perform statistical analyses averaging on different level of human interaction across Europe and with the rest of the World. Our results are neatly summarised as an animation reporting the time evolution of the first and second waves of the European COVID-19 pandemic. Our temporal playbook of the second wave pandemic can be used by governments, financial markets, the industries and individual citizens, to efficiently time, prepare and implement local and global measures.
Structural and vibrational properties of agrellite
Authors: Kaneva Ekaterina , Bogdanov Alexandr , Shendrik Roman
Published: September 2020

Agrellite, NaCa2Si4O10F, is a tubular silicate mineral which crystal structure is characterized by extended [Si8O20]8– tubes and has a two-dimensional channel system. The mineral is a representative of a complex silicate family which contains some structural voids but cannot be considered as microporous because of small channel widths. However, the channel system of such minerals is able to host single guest atoms, molecules or radicals which can affect their physical properties. Presently, the exact mechanism of such hosting is undetermined. However, such information could be quite useful for materials’ application as zeolites as well as for a better understanding of their formation mechanisms. In this work we couple X-ray diffraction, infrared (IR) spectroscopy and ab initio calculations to identify structural features in agrellite from Malyy Murun massif (Russia) caused by incorporation of either H2O or OH− into the channel system. We construct structural models of water-containing NaCa2Si4O10F and identified H2O positions. The derivation of H2O sites is based on simulation of IR-spectra. Infrared spectroscopy in combination with the ab initio calculation has proven to be an effective tool for the identification of the structural positions of hydroxyl anions (OH−) and neutral water groups (H2O) in minerals.
How to do quantile normalization correctly for gene expression data analyses
Authors: Zhao Yaxing , Wong Limsoon , Goh Wilson Wen Bin
Published: September 2020

Quantile normalization is an important normalization technique commonly used in high-dimensional data analysis. However, it is susceptible to class-effect proportion effects (the proportion of class-correlated variables in a dataset) and batch effects (the presence of potentially confounding technical variation) when applied blindly on whole data sets, resulting in higher false-positive and false-negative rates. We evaluate five strategies for performing quantile normalization, and demonstrate that good performance in terms of batch-effect correction and statistical feature selection can be readily achieved by first splitting data by sample class-labels before performing quantile normalization independently on each split (“Class-specific”). Via simulations with both real and simulated batch effects, we demonstrate that the “Class-specific” strategy (and others relying on similar principles) readily outperform whole-data quantile normalization, and is robust-preserving useful signals even during the combined analysis of separately-normalized datasets. Quantile normalization is a commonly used procedure. But when carelessly applied on whole datasets without first considering class-effect proportion and batch effects, can result in poor performance. If quantile normalization must be used, then we recommend using the “Class-specific” strategy.
Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging
Authors: Ryu Shoraku , Ohuchi Mayu , Yagishita Shigehiro , Shimoi Tatsunori , Yonemori Kan , Tamura Kenji , Fujiwara Yasuhiro , Hamada Akinobu
Published: September 2020

Penetration of nanoparticles into viable tumor regions is essential for an effective response. Mass spectrometry imaging (MSI) is a novel method for evaluating the intratumoral pharmacokinetics (PK) of a drug in terms of spatial distribution. The application of MSI for analysis of nanomedicine PK remains in its infancy. In this study, we evaluated the applicability of MALDI-MSI for nanoparticle-formulated drug visualization in tumors and biopsies, with an aim toward future application in clinical nanomedicine research. We established an analytic method for the free drug (AZD2811) and then applied it to visualize nanoparticle-formulated AZD2811. MSI analysis demonstrated heterogeneous intratumoral drug distribution in three xenograft tumors. The intensity of MSI signals correlated well with total drug concentration in tumors, indicating that drug distribution can be monitored quantitatively. Analysis of tumor biopsies indicated that MSI is applicable for analyzing the distribution of nanoparticle-formulated drugs in tumor biopsies, suggesting clinical applicability.
Omega-3 fatty acid prevents the development of heart failure by changing fatty acid composition in the heart
Authors: Toko Haruhiro , Morita Hiroyuki , Katakura Masanori , Hashimoto Michio , Ko Toshiyuki , Bujo Satoshi , Adachi Yusuke , Ueda Kazutaka , Murakami Haruka , Ishizuka Masato , Guo Jiaxi , Zhao Chunxia , Fujiwara Takayuki , Hara Hironori , Takeda Norifumi , Takimoto Eiki , Shido Osamu , Harada Mutsuo , Komuro Issei
Published: September 2020

Some clinical trials showed that omega-3 fatty acid (FA) reduced cardiovascular events, but it remains unknown whether omega-3 FA supplementation changes the composition of FAs and their metabolites in the heart and how the changes, if any, exert beneficial effects on cardiac structure and function. To clarify these issues, we supplied omega-3 FA to mice exposed to pressure overload, and examined cardiac structure and function by echocardiography and a proportion of FAs and their metabolites by gas chromatography and liquid chromatography-tandem mass spectrometry, respectively. Pressure overload induced cardiac hypertrophy and dysfunction, and reduced concentration of all FAs’ components and increased free form arachidonic acid and its metabolites, precursors of pro-inflammatory mediators in the heart. Omega-3 FA supplementation increased both total and free form of eicosapentaenoic acid, a precursor of pro-resolution mediators and reduced free form arachidonic acid in the heart. Omega-3 FA supplementation suppressed expressions of pro-inflammatory cytokines and the infiltration of inflammatory cells into the heart and ameliorated cardiac dysfunction and fibrosis. These results suggest that omega-3 FA-induced changes of FAs composition in the heart have beneficial effects on cardiac function via regulating inflammation.
The fatty-acid amide hydrolase inhibitor URB597 inhibits MICA/B shedding
Authors: Sekiba Kazuma , Otsuka Motoyuki , Seimiya Takahiro , Tanaka Eri , Funato Kazuyoshi , Miyakawa Yu , Koike Kazuhiko
Published: September 2020

MICA/B proteins are expressed on the surface of various types of stressed cells, including cancer cells. Cytotoxic lymphocytes expressing natural killer group 2D (NKG2D) receptor recognize MICA/B and eliminate the cells. However, cancer cells evade such immune recognition by inducing proteolytic shedding of MICA/B proteins. Therefore, preventing the shedding of MICA/B proteins could enhance antitumor immunity. Here, by screening a protease inhibitor library, we found that the fatty-acid amide hydrolase (FAAH) inhibitor, URB597, suppresses the shedding of MICA/B. URB597 significantly reduced the soluble MICA level in culture medium and increased the MICA level on the surface of cancer cells. The effect was indirect, being mediated by increased expression of tissue inhibitor of metalloproteinases 3 (TIMP3). Knockdown of TIMP3 expression reversed the effect of URB597, confirming that TIMP3 is required for the MICA shedding inhibition by URB597. In contrast, FAAH overexpression reduced TIMP3 expression and the cell-surface MICA level and increased the soluble MICA level. These results suggest that inhibition of FAAH could prevent human cancer cell evasion of immune-mediated clearance.
Ornithine and breast cancer: a matched case–control study
Authors: Zhang Jiayi , Tao Baihui , Chong Yiran , Ma Shuang , Wu Gang , Zhu Hailong , Zhao Yi , Zhao Shitao , Niu Mengmeng , Zhang Shutian , Wang Tianyi , Yang Shuman , Qiao Wenjing , Vuong Ann M. , Li Jincheng , Zhu Demiao , Tao Wei
Published: September 2020

In vivo and vitro evidence indicates that ornithine and its related metabolic products play a role in tumor development. Whether ornithine is associated with breast cancer in humans is still unclear. We examined the association between circulating ornithine levels and breast cancer in females. This 1:1 age-matched case–control study identified 735 female breast cancer cases and 735 female controls without breast cancer. All cases had a pathological test to ascertain a breast cancer diagnosis. The controls were ascertained using pathologic testing, clinical examinations, and/or other tests. Fasting blood samples were used to measure ornithine levels. The average age for cases and controls were 49.6 years (standard deviation [SD] 8.7 years) and 48.9 years (SD 8.7 years), respectively. Each SD increase in ornithine levels was associated with a 12% reduction of breast cancer risk (adjusted odds ratio [OR] 0.88; 95% confidence interval [CI] 0.79–0.97). The association between ornithine and breast cancer did not differ by pathological stages of diagnosis or tumor grades (all P for trend > 0.1). We observed no effect measure modification by molecular subtypes (P for interaction = 0.889). In conclusion, higher ornithine levels were associated with lower breast cancer risk in females.
Author Correction: Electromyographic activity of the vastus medialis and gastrocnemius implicates a slow stretch-shortening cycle during rowing in the field
Authors: Held Steffen , Siebert Tobias , Donath Lars
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mitochondria-targeted fluorescent probe for imaging endogenous hydrogen sulfide in cellular antioxidant stress
Authors: Cai Songtao , Liu Chang , He Song , Zhao Liancheng , Zeng Xianshun
Published: September 2020

The mitochondria-targeted fluorescence probe L, a thioxanthene-benzoindole derivative, for the detection and imaging of endogenous H2S in living cells and cellular antioxidant stress has been developed.
Designing signal-on sensors by regulating nanozyme activity
Authors: Chang Yangyang , Gao Sheng , Liu Meng , Liu Juewen
Published: September 2020

Nanozymes can be used to detect its promotors or molecules that can specifically remove their inhibitors. In both cases, ‘signal-on’ sensors are produced.
Zinc ferrite-based p–n homojunction with multi-effect for efficient photoelectrochemical water splitting
Authors: Han Jianhua , Lan Yayao , Song Qinggong , Yan Huiyu , Kang Jianhai , Guo Yanrui , Liu Zhifeng
Published: September 2020

A novel homojunction is constructed by decorating p-type Ni-ZnFe2O4 (shell) onto n-type ZnFe2O4 (core) for efficient photoelectrochemical water splitting.
CRISPR-Cas12a trans-cleaves DNA G-quadruplexes
Authors: Li Ying , Li Tao , Liu Bi-Feng , Hu Rui , Zhu Jiang , He Ting , Zhou Xin , Li Conggang , Yang Yunhuang , Liu Maili
Published: September 2020

CRISPR-Cas12a trans-cleaves DNA G-quadruplexes after activation.
Strategies to control product characteristics in simultaneous crystallization of NaCl and KCl from aqueous solution: seeding with NaCl and KCl
Authors: Penha F. M. , Zago G. P. , Seckler M. M.
Published: September 2020

In this work we developed an approach for the simultaneous crystallization of NaCl and KCl from their aqueous solution by concomitantly seeding both salts. Results highlight the possibility of retrieving relatively pure solid fractions of each salt.
Designing positive electrodes based on 3D hierarchical CoMn2O4@NiMn-LDH nanoarray composites for high energy and power density supercapacitors
Authors: Meng Suci , Wang Yintao , Zhang Yuqi , Xu Qing , Jiang Deli , Chen Min
Published: September 2020

3D hierarchical CoMn2O4@NiMn-LDH core–shell nanowire arrays as positive electrodes for high energy and power density supercapacitors.
Synthesis of a novel one-dimensional Bi2O2CO3–BiOCl heterostructure and its enhanced photocatalytic activity
Authors: Peng Yin , Zhang Qian , Kan Peng-Fei
Published: September 2020

A novel one-dimensional Bi2O2CO3–BiOCl heterostructure was synthesized. BiOCl nanosheets uniformly and vertically grew onto the Bi2O2CO3 porous rods via crystallographic oriented epitaxial nucleation and growth. Bi2O2CO3–BiOCl displayed excellent photocatalytic activity.
Functionalisation of gold nanoparticles with ruthenium(ii) polypyridyl complexes for their application in cellular imaging
Authors: Estalayo-Adrián Sandra , McManus Gavin J. , Dalton Hannah L. , Savyasachi Aramballi J. , Kelly John M. , Gunnlaugsson Thorfinnur
Published: September 2020

Two new dinuclear Ru(ii) polypyridyl complexes containing an alkyl disulphide functionalised bipyridine-based ligand and either 1,10-phenanthroline (phen) or 1,4,5,8-tetraazaphenanthrene (TAP) ligands were developed.
Nanoparticle size and natural organic matter composition determine aggregation behavior of polyvinylpyrrolidone coated platinum nanoparticles
Authors: Sikder Mithun , Wang Jingjing , Poulin Brett A. , Tfaily Malak M. , Baalousha Mohammed
Published: September 2020

Engineered nanoparticle (NP) size and natural organic matter (NOM) composition play important roles in determining NP environmental behaviors.
Chrysanthemum ethanol extract induced loss of Kupffer cellsviathe mitochondria-dependent apoptotic pathway
Authors: Liang Wan-Li , Wen Yanzhang , Huang Fang , Hu Qin , Li Xiao-Jun , Zhang Wei Kevin , Yang Xinzhou
Published: September 2020

The current study indicated a potential safety issue of the daily consumption of chrysanthemum.
A novel method for measuring ultra-trace levels of U and Th in Au, Pt, Ir, and W matrices using ICP-QQQ-MS employing an O2 reaction gas
Authors: Harouaka Khadouja , Hoppe Eric W. , Arnquist Isaac J.
Published: September 2020

A mass shift method using ICP-MS/MS with O2 reaction gas is used for ultra-trace determinations of U and Th in samples containing W, Ir, Pt, and Au derived polyatomic interferants without the need for extensive chemical sample preprocessing.
Origin of stereoselectivity in an isothiourea catalyzed Michael addition reaction of aryl ester with vinyl disulfone
Authors: Wang Congcong , Li Shi-Jun , Zhang Min , Wei Donghui , Ding Lina
Published: September 2020

The origin of stereoselectivity in an isothiourea-catalyzed addition reaction of aryl ester with vinyl disulfone was explored for the first time.
The vital role of ditopic N–N bridging ligands with different lengths in the formation of new binuclear dioxomolybdenum(vi) complexes: synthesis, crystal structures, supramolecular framework and protein binding studies
Authors: Biswal Debanjana , Roy Malini , Pramanik Nikhil Ranjan , Paul Suvendu , Drew Michael G. B. , Chakrabarti Syamal
Published: September 2020

Role of bis-(pyridyl) and bis-(imidazole) auxiliary ligands in the formation of supramolecular architectures and BSA binding with new binuclear dioxomolybdenum(vi) complexes.
Tailoring capacitance of 3D-printed graphene electrodes by carbonisation temperature
Authors: Redondo Edurne , Ng Siowwoon , Muñoz Jose , Pumera Martin
Published: September 2020

The carbonisation temperature has shown to be a key activation parameter to modulate the capacitive performance of graphene-based 3D-printed nanocomposite electrodes.
Ultra-high drivability, high-mobility, low-voltage and high-integration intrinsically stretchable transistors
Authors: Huang Weihong , Jiao Haoxuan , Huang Qiuyue , Zhang Jiaona , Zhang Min
Published: September 2020

Realizing intrinsically stretchable transistors with high current drivability, high mobility, small feature size, low power and the potential for mass production is essential for advancing stretchable electronics a critical step forward.
Nanobowtie arrays with tunable materials and geometries fabricated by holographic lithography
Authors: Liu Bowen , Zhan Chao , Yao Xu , Yan Sen , Ren Bin
Published: September 2020

A novel method to fabricate nanobowtie arrays over large areas with the advantages of tunable gap size, material and architecture.
Unveiling the influence of surrounding materials and realization of multi-level storage in resistive switching memory
Authors: Chang Kuan-Chang , Dai Tianjiao , Li Lei , Lin Xinnan , Zhang Shengdong , Lai Ying-Chih , Liu Heng-Jui , Syu Yong-En
Published: September 2020

This work investigated the influence of surrounding material on RRAM and offered a strategy to achieve multilevel storage functionality with superior scalability and stability, suggesting its potential to be applied in neuromorphic computing area.
Highly conductive PEDOT:PSS film made with ethylene-glycol addition and heated-stir treatment for enhanced photovoltaic performances
Authors: Wei Ta-Cheng , Chen Shih-Hsiu , Chen Chia-Yun
Published: September 2020

Highly conductive and stable PEDOT:PSS films prepared by ethylene-glycol addition and heated-stir treatment offer improved photovoltaic performances.
A facile and green synthesis approach to derive highly stable SiOx-hard carbon based nanocomposites for use as the anode in lithium-ion batteries
Authors: Dora Jay Krishan , Nayak Debasis , Ghosh Sudipto , Adyam Venimadhav , Yedla Natraj , Kundu Tarun Kumar
Published: September 2020

We present an efficient synthesis technique to derive highly stable anode for lithium-ion batteries.
Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery
Authors: Zheng Tongyin , Yang Yiran , Castañeda Carlos A.
Published: September 2020

Cells rely on protein homeostasis to maintain proper biological functions. Dysregulation of protein homeostasis contributes to the pathogenesis of many neurodegenerative diseases and cancers. Ubiquilins (UBQLNs) are versatile proteins that engage with many components of protein quality control (PQC) machinery in cells. Disease-linked mutations of UBQLNs are most commonly associated with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative disorders. UBQLNs play well-established roles in PQC processes, including facilitating degradation of substrates through the ubiquitin–proteasome system (UPS), autophagy, and endoplasmic-reticulum-associated protein degradation (ERAD) pathways. In addition, UBQLNs engage with chaperones to sequester, degrade, or assist repair of misfolded client proteins. Furthermore, UBQLNs regulate DNA damage repair mechanisms, interact with RNA-binding proteins (RBPs), and engage with cytoskeletal elements to regulate cell differentiation and development. Important to the myriad functions of UBQLNs are its multidomain architecture and ability to self-associate. UBQLNs are linked to numerous types of cellular puncta, including stress-induced biomolecular condensates, autophagosomes, aggresomes, and aggregates. In this review, we focus on deciphering how UBQLNs function on a molecular level. We examine the properties of oligomerization-driven interactions among the structured and intrinsically disordered segments of UBQLNs. These interactions, together with the knowledge from studies of disease-linked mutations, provide significant insights to UBQLN structure, dynamics and function.
Benefits of a Hearing Registry: Cochlear Implant Candidacy in Quiet Versus Noise in 1,611 Patients
Authors: Dunn Camille , Miller Sharon E. , Schafer Erin C. , Silva Christopher , Gifford René H. , Grisel Jedidiah J.
Published: September 2020

Purpose

This retrospective study used a cochlear implant registry to determine how performing speech recognition candidacy testing in quiet versus noise influenced patient selection, speech recognition, and self-report outcomes.

Method

Database queries identified 1,611 cochlear implant recipients who were divided into three implant candidacy qualifying groups based on preoperative speech perception scores (≤ 40% correct) on the AzBio sentence test: quiet qualifying group, +10 dB SNR qualifying group, and +5 dB SNR qualifying group. These groups were evaluated for demographic and preoperative hearing characteristics. Repeated-measures analysis of variance was used to compare pre- and postoperative performance on the AzBio in quiet and noise with qualifying group as a between-subjects factor. For a subset of recipients, pre- to postoperative changes on the Speech, Spatial and Qualities of Hearing Scale were also evaluated.

Results

Of the 1,611 patients identified as cochlear implant candidates, 63% of recipients qualified in quiet, 10% qualified in a +10 dB SNR, and 27% qualified in a +5 dB SNR. Postoperative speech perception scores in quiet and noise significantly improved for all qualifying groups. Across qualifying groups, the greatest speech perception improvements were observed when tested in the same qualifying listening condition. For a subset of patients, the total Speech, Spatial and Qualities of Hearing Scale ratings improved significantly as well.

Conclusion

Patients who qualified for cochlear implantation in quiet or background noise test conditions showed significant improvement in speech perception and quality of life scores, especially when the qualifying noise condition was used to track performance.