bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint Geophysical‐Petrological Modeling on the Ivrea Geophysical Body Beneath Valsesia, Italy: Constraints on the Continental Lower Crust
Authors: Pistone Mattia , Ziberna Luca , Hetényi György , Scarponi Matteo , Zanetti Alberto , Müntener Othmar
Published: November 2020

One of the few near‐complete continental crustal sections exposed on Earth's surface is the Ivrea‐Verbano Zone (Western Alps, Italy), which is considered as a petro‐geophysical reference of the continental lithosphere. Exposed peridotite slivers embedded in lower crustal rocks at the surface and large density, seismic velocity anomalies of the Ivrea Geophysical Body in the subsurface suggest that mantle‐like rocks are located as shallow as a few kilometers depth, but the actual composition of the rocks producing these anomalies is unknown. Here we investigate how the published seismological and new gravimetric data in the location of Valsesia could be reconciled with petrologic data and models of the Ivrea‐Verbano Zone. We use the Perple_X software to calculate densities and compressional wave velocities for a range of possible deep crustal rock types. We argue that amphibole gabbros (<18 km depth) and pyroxene hornblendites (>18 km depth) provide the best fit to the joint geophysical and petrologic constraints, whereas residual ultramafic rocks and anhydrous gabbros are inconsistent with the existing data. This indicates that the Ivrea Geophysical Body beneath the Valsesia area in the Ivrea‐Verbano Zone preserves the structure of an igneous complex formed during magmatic underplating from the crystallization of hydrous mafic magmas. This would imply melting of a damp mantle source that produced a continental crust of an original thickness of up to ∼48 km in the Permian, of which ∼30 km are exposed at Earth's surface today.
A Subgrain‐Size Piezometer Calibrated for EBSD
Authors: Goddard R. M. , Hansen L. N. , Wallis D. , Stipp M. , Holyoke C. W. , Kumamoto K. M. , Kohlstedt D. L.
Published: November 2020

We calibrate a subgrain‐size piezometer using electron backscatter diffraction (EBSD) data collected from experimentally deformed samples of olivine and quartz. Systematic analyses of angular and spatial resolution test the suitability of each data set for inclusion in calibration of the subgrain‐size piezometer. To identify subgrain boundaries, we consider a range of critical misorientation angles and conclude that a 1° threshold provides the optimal piezometric calibration. The mean line‐intercept length, equivalent to the subgrain‐size, is found to be inversely proportional to the von Mises equivalent stress for data sets both with and without the correction of Holyoke and Kronenberg (2010, https://doi.org/10.1016/j.tecto.2010.08.001). These new piezometers provide stress estimates from EBSD analyses of polymineralic rocks without the need to discriminate between relict and recrystallized grains and therefore greatly increase the range of rocks that may be used to constrain geodynamic models.
Enhanced Meiyu‐Baiu Rainfall in Early Summer 2020: Aftermath of the 2019 Super IOD Event
Authors: Takaya Yuhei , Ishikawa Ichiro , Kobayashi Chiaki , Endo Hirokazu , Ose Tomoaki
Published: November 2020

In early summer 2020, the Meiyu‐Baiu rainfall was markedly enhanced, triggering devastating floods in Japan and central China. We examined the underlying processes using a climate model and analysis. The enhanced Meiyu‐Baiu rainfall was reasonably predicted by the climate model initialized at the end of April. The sensitivity experiment indicated that Indian Ocean (IO) warming enhanced the Meiyu‐Baiu rainfall. Moreover, we found that the warm IO condition can be traced back to the super Indian Ocean Dipole (IOD) in 2019. The IO warmth was influenced by successive processes: record strong downwelling Rossby waves excited by the IOD and tripole sea surface temperature anomalies in the tropical IO‐western Pacific, their arrival to the southwestern IO in spring, and associated modulation of monsoon flow. The results suggest that the seasonal predictability of the Meiyu‐Baiu rainfall in 2020 originated from the super IOD.
Colocated Observations of the E and F Region Thermosphere During a Substorm
Authors: Billett D. D. , McWilliams K. A. , Conde M. G.
Published: November 2020

Two‐dimensional thermospheric wind fields, at both E and F region altitudes within a common vertical volume, were made using a Scanning Doppler Imager (SDI) at Poker Flat, Alaska, during a substorm event. Coinciding with these observations were F region plasma velocity measurements from the Super Dual Auroral Radar Network (SuperDARN) and estimations of the total downward and upward field‐aligned current density from the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). This combination of instruments gives an excellent opportunity to examine the spatial characteristics of high‐latitude ionosphere‐thermosphere coupling and how a process which is triggered in the magnetosphere (the substorm) affects that coupling at different altitudes. We find that during the substorm growth phase, the F region thermospheric winds respond readily to an expanding ionospheric plasma convection pattern, while the E region winds appear to take a much longer period of time. The differing response timescales of the E and F region winds are likely due to differences in neutral density at those altitudes, resulting in E region neutrals being much more “sluggish” with regard to ion drag. We also observe increases in the F region neutral temperature, associated with neutral winds accelerating during both substorm growth and recovery phases.
Antenatal corticosteroids: a reappraisal of the drug formulation and dose
Authors: Jobe Alan H. , Kemp Matthew , Schmidt Augusto , Takahashi Tsukasa , Newnham John , Milad Mark
Published: November 2020

We review the history of antenatal corticosteroid therapy (ACS) and present recent experimental data to demonstrate that this, one of the pillars of perinatal care, has been inadequately evaluated to minimize fetal exposure to these powerful medications. There have been concerns since 1972 that fetal exposures to ACS convey risk. However, this developmental modulator, with its multiple widespread biologic effects, has not been evaluated for drug choice, dose, or duration of treatment, despite over 30 randomized trials. The treatment used in the United States is two intramuscular doses of a mixture of 6 mg betamethasone phosphate (Beta P) and 6 mg betamethasone acetate (Beta Ac). To optimize outcomes with ACS, the goal should be to minimize fetal drug exposure. We have determined that the minimum exposure needed for fetal lung maturation in sheep, monkeys, and humans (based on published cord blood corticosteroid concentrations) is about 1 ng/ml for a 48-h continuous exposure, far lower than the concentration reached by the current dosing. Because the slowly released Beta Ac results in prolonged fetal exposure, a drug containing Beta Ac is not ideal for ACS use.

Impact

Using sheep and monkey models, we have defined the minimum corticosteroid exposure for a fetal lung maturation.

These results should generate new clinical trials of antenatal corticosteroids (ACS) at much lower fetal exposures to ACS, possibly given orally, with fewer risks for the fetus.
Examining cognitive change in magnetic resonance-guided focused ultrasound capsulotomy for psychiatric illness
Authors: Davidson Benjamin , Hamani Clement , Meng Ying , Baskaran Anusha , Sharma Sachie , Abrahao Agessandro , Richter Margaret Anne , Levitt Anthony , Giacobbe Peter , Lipsman Nir , Rabin Jennifer S.
Published: November 2020

Magnetic resonance-guided focused ultrasound (MRgFUS) anterior capsulotomy is a novel treatment option for patients with refractory obsessive compulsive disorder (OCD) or major depressive disorder (MDD). However, there is concern that lesional psychiatric surgery procedures may have adverse effects on cognition. In this study, we examined whether MRgFUS capsulotomy causes cognitive decline in patients with psychiatric illness. Ten patients with refractory OCD (n = 5) or MDD (n = 5) underwent MRgFUS capsulotomy. Cognitive functioning was measured at baseline as well as 6 months and 12 months postoperatively, with a battery of neuropsychological tests assessing domains of executive function, memory, and processing speed. Scores were analyzed at the individual-level, and changes ≥2 standard deviations were considered clinically significant. We also examined whether changes in clinical symptoms were associated with changes in cognitive performance. At baseline intellectual functioning was in the average to high-average range for the group. Following MRgFUS capsulotomy, there were no deteriorations in cognition that reached ≥2 standard deviations at 6 or 12 months. Eight out of ten patients demonstrated a ≥2 standard deviation improvement in at least one cognitive score at 6 or 12 months postoperatively. Improvements in clinical symptoms correlated significantly with self-reported improvements in frontal lobe function (p < 0.05), but not with objective measures of cognitive functioning. To summarize, MRgFUS capsulotomy did not result in cognitive decline in this cohort of patients with refractory OCD or MDD, suggesting that this procedure can be offered to patients with a very low risk of cognitive side effects.
Cancer cell metabolic reprogramming: a keystone for the response to immunotherapy
Authors: Cerezo Michaël , Rocchi Stéphane
Published: November 2020

By targeting the tumor microenvironment to stimulate antitumor immunity, immunotherapies have revolutionized cancer treatment. However, many patients do not respond initially or develop secondary resistance. Based on the limited resources in the tumor microenvironment and competition between tumor and immune cells, the field of immune metabolism has produced extensive knowledge showing that targeting metabolism could help to modulate antitumor immunity. However, among all the different potentially targetable metabolic pathways, it remains unclear which have more potential to overcome resistance to immune checkpoint inhibitors. Here, we explore metabolic reprogramming in cancer cells, which might inhibit antitumor immunity, and strategies that can be used to favor the antitumor response.
IL-22 ameliorates LPS-induced acute liver injury by autophagy activation through ATF4-ATG7 signaling
Authors: Shao Lujing , Xiong Xi , Zhang Yucai , Miao Huijie , Ren Yuqian , Tang Xiaomeng , Song Jia , Wang Chunxia
Published: November 2020

Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the underlying mechanisms of IL-22 involved in lipopolysaccharide (LPS) - induced acute liver injury (ALI) in mice. Serum IL-22 levels in patients with SALI were significantly lower than in septic patients without liver injury, and the area under receiver operating characteristic (ROC) curve of IL-22 for discriminating SALI was 0.765 (95% CI: 0.593–0.937). Pre-administration of recombinant murine IL-22 alleviated LPS-induced ALI in mice, and serum IL-6 levels and the mRNA levels of TNF-α, IL-1β, and IL-6 in livers were decreased in response to IL-22 pre-treatment in mice. More importantly, IL-22 pre-treatment activated hepatic autophagy mediated by activating transcription factor 4 (ATF4)-autophagy-related gene 7 (ATG7) signaling in vivo and in vitro in response to LPS administration. Moreover, knockdown of ATF4 in mice aggravated LPS-induced ALI, which was associated with suppressed ATG7-related autophagy. In addition, the protective effects of IL-22 on LPS-induced ALI was partially blocked by ATF4 knockdown, which was associated with lower expression of LC3II/I in the livers of ATF4 knockdown (HT or Atf4+/−) mice compared with wild-type mice (WT or Atf4+/+) mice. In conclusion, low serum IL-22 level is associated with SALI occurrence, and IL-22 pre-administration activates autophagy in hepatocytes and protects mice against LPS-induced ALI partially related to ATF4-ATG7 signaling pathway.
MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity
Authors: Hanada Yuki , Ishihara Naotada , Wang Lixiang , Otera Hidenori , Ishihara Takaya , Koshiba Takumi , Mihara Katsuyoshi , Ogawa Yoshihiro , Nomura Masatoshi
Published: November 2020

Mitochondria are multifunctional organelles that produce energy and are critical for various signaling pathways. Mitochondrial antiviral signaling (MAVS) is a mitochondrial outer membrane protein essential for the anti-RNA viral immune response, which is regulated by mitochondrial dynamics and energetics; however, the molecular link between mitochondrial metabolism and immunity is unclear. Here we show in cultured mammalian cells that MAVS is activated by mitochondrial fission factor (Mff), which senses mitochondrial energy status. Mff mediates the formation of active MAVS clusters on mitochondria, independent of mitochondrial fission and dynamin-related protein 1. Under mitochondrial dysfunction, Mff is phosphorylated by the cellular energy sensor AMP-activated protein kinase (AMPK), leading to the disorganization of MAVS clusters and repression of the acute antiviral response. Mff also contributes to immune tolerance during chronic infection by disrupting the mitochondrial MAVS clusters. Taken together, Mff has a critical function in MAVS-mediated innate immunity, by sensing mitochondrial energy metabolism via AMPK signaling.
The cryo-EM structure of a γ-TuSC elucidates architecture and regulation of minimal microtubule nucleation systems
Authors: Zupa Erik , Zheng Anjun , Neuner Annett , Würtz Martin , Liu Peng , Böhler Anna , Schiebel Elmar , Pfeffer Stefan
Published: November 2020

The nucleation of microtubules from αβ-tubulin subunits is mediated by γ-tubulin complexes, which vary in composition across organisms. Aiming to understand how de novo microtubule formation is achieved and regulated by a minimal microtubule nucleation system, we here determined the cryo-electron microscopy structure of the heterotetrameric γ-tubulin small complex (γ-TuSC) from C. albicans at near-atomic resolution. Compared to the vertebrate γ-tubulin ring complex (γ-TuRC), we observed a vastly remodeled interface between the SPC/GCP-γ-tubulin spokes, which stabilizes the complex and defines the γ-tubulin arrangement. The relative positioning of γ-tubulin subunits indicates that a conformational rearrangement of the complex is required for microtubule nucleation activity, which follows opposing directionality as predicted for the vertebrate γ-TuRC. Collectively, our data suggest that the assembly and regulation mechanisms of γ-tubulin complexes fundamentally differ between the microtubule nucleation systems in lower and higher eukaryotes.
Electrochemical deposition of N-heterocyclic carbene monolayers on metal surfaces
Authors: Amit Einav , Dery Linoy , Dery Shahar , Kim Suhong , Roy Anirban , Hu Qichi , Gutkin Vitaly , Eisenberg Helen , Stein Tamar , Mandler Daniel , Dean Toste F. , Gross Elad
Published: November 2020

N-heterocyclic carbenes (NHCs) have been widely utilized for the formation of self-assembled monolayers (SAMs) on various surfaces. The main methodologies for preparation of NHCs-based SAMs either requires inert atmosphere and strong base for deprotonation of imidazolium precursors or the use of specifically-synthesized precursors such as NHC(H)[HCO3] salts or NHC–CO2 adducts. Herein, we demonstrate an electrochemical approach for surface-anchoring of NHCs which overcomes the need for dry environment, addition of exogenous strong base or restricting synthetic steps. In the electrochemical deposition, water reduction reaction is used to generate high concentration of hydroxide ions in proximity to a metal electrode. Imidazolium cations were deprotonated by hydroxide ions, leading to carbenes formation that self-assembled on the electrode’s surface. SAMs of NO2-functionalized NHCs and dimethyl-benzimidazole were electrochemically deposited on Au films. SAMs of NHCs were also electrochemically deposited on Pt, Pd and Ag films, demonstrating the wide metal scope of this deposition technique.
Organized cannabinoid receptor distribution in neurons revealed by super-resolution fluorescence imaging
Authors: Li Hui , Yang Jie , Tian Cuiping , Diao Min , Wang Quan , Zhao Simeng , Li Shanshan , Tan Fangzhi , Hua Tian , Qin Ya , Lin Chao-Po , Deska-Gauthier Dylan , Thompson Garth J. , Zhang Ying , Shui Wenqing , Liu Zhi-Jie , Wang Tong , Zhong Guisheng
Published: November 2020

G-protein-coupled receptors (GPCRs) play important roles in cellular functions. However, their intracellular organization is largely unknown. Through investigation of the cannabinoid receptor 1 (CB1), we discovered periodically repeating clusters of CB1 hotspots within the axons of neurons. We observed these CB1 hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB1 signaling. Furthermore, we found that CB1 hotspot periodicity increased upon CB1 agonist application, and these activated CB1 displayed less dynamic movement compared to non-activated CB1. Our results suggest that CB1 forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy upon activation.
TranSPHIRE: automated and feedback-optimized on-the-fly processing for cryo-EM
Authors: Stabrin Markus , Schoenfeld Fabian , Wagner Thorsten , Pospich Sabrina , Gatsogiannis Christos , Raunser Stefan
Published: November 2020

Single particle cryo-EM requires full automation to allow high-throughput structure determination. Although software packages exist where parts of the cryo-EM pipeline are automated, a complete solution that offers reliable on-the-fly processing, resulting in high-resolution structures, does not exist. Here we present TranSPHIRE: A software package for fully-automated processing of cryo-EM datasets during data acquisition. TranSPHIRE transfers data from the microscope, automatically applies the common pre-processing steps, picks particles, performs 2D clustering, and 3D refinement parallel to image recording. Importantly, TranSPHIRE introduces a machine learning-based feedback loop to re-train its picking model to adapt to any given data set live during processing. This elegant approach enables TranSPHIRE to process data more effectively, producing high-quality particle stacks. TranSPHIRE collects and displays all metrics and microscope settings to allow users to quickly evaluate data during acquisition. TranSPHIRE can run on a single work station and also includes the automated processing of filaments.
The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice
Authors: Yesbolatova Aisha , Saito Yuichiro , Kitamoto Naomi , Makino-Itou Hatsune , Ajima Rieko , Nakano Risako , Nakaoka Hirofumi , Fukui Kosuke , Gamo Kanae , Tominari Yusuke , Takeuchi Haruki , Saga Yumiko , Hayashi Ken-ichiro , Kanemaki Masato T.
Published: November 2020

Protein knockdown using the auxin-inducible degron (AID) technology is useful to study protein function in living cells because it induces rapid depletion, which makes it possible to observe an immediate phenotype. However, the current AID system has two major drawbacks: leaky degradation and the requirement for a high dose of auxin. These negative features make it difficult to control precisely the expression level of a protein of interest in living cells and to apply this method to mice. Here, we overcome these problems by taking advantage of a bump-and-hole approach to establish the AID version 2 (AID2) system. AID2, which employs an OsTIR1(F74G) mutant and a ligand, 5-Ph-IAA, shows no detectable leaky degradation, requires a 670-times lower ligand concentration, and achieves even quicker degradation than the conventional AID. We demonstrate successful generation of human cell mutants for genes that were previously difficult to deal with, and show that AID2 achieves rapid target depletion not only in yeast and mammalian cells, but also in mice.
Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19
Authors: Tosif Shidan , Neeland Melanie R. , Sutton Philip , Licciardi Paul V. , Sarkar Sohinee , Selva Kevin J. , Do Lien Anh Ha , Donato Celeste , Quan Toh Zheng , Higgins Rachel , Van de Sandt Carolien , Lemke Melissa M. , Lee Christina Y. , Shoffner Suzanne K. , Flanagan Katie L. , Arnold Kelly B. , Mordant Francesca L. , Mulholland Kim , Bines Julie , Dohle Kate , Pellicci Daniel G. , Curtis Nigel , McNab Sarah , Steer Andrew , Saffery Richard , Subbarao Kanta , Chung Amy W. , Kedzierska Katherine , Burgner David P. , Crawford Nigel W.
Published: November 2020

Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.
Review of corrosion interactions between different materials relevant to disposal of high-level nuclear waste
Authors: Guo Xiaolei , Gin Stephane , Frankel Gerald S.
Published: November 2020

This review covers the corrosion interactions between different materials that are relevant to the disposal of high-level nuclear waste, in particular the waste forms and containers. The materials of interest are borosilicate glass, crystalline ceramics, metal alloys, and any corrosion products that might form. The available data show that these interactions depend on the structure, chemistry, thermodynamic history, and proximity of the materials in contact, as well as the environmental attributes, such as temperature, solution chemistry, and radiation. Several key mechanisms that govern these interactions are highlighted. Scientific gaps and open questions are summarized and discussed.
A band-gap database for semiconducting inorganic materials calculated with hybrid functional
Authors: Kim Sangtae , Lee Miso , Hong Changho , Yoon Youngchae , An Hyungmin , Lee Dongheon , Jeong Wonseok , Yoo Dongsun , Kang Youngho , Youn Yong , Han Seungwu
Published: November 2020

Semiconducting inorganic materials with band gaps ranging between 0 and 5 eV constitute major components in electronic, optoelectronic and photovoltaic devices. Since the band gap is a primary material property that affects the device performance, large band-gap databases are useful in selecting optimal materials in each application. While there exist several band-gap databases that are theoretically compiled by density-functional-theory calculations, they suffer from computational limitations such as band-gap underestimation and metastable magnetism. In this data descriptor, we present a computational database of band gaps for 10,481 materials compiled by applying a hybrid functional and considering the stable magnetic ordering. For benchmark materials, the root-mean-square error in reference to experimental data is 0.36 eV, significantly smaller than 0.75–1.05 eV in the existing databases. Furthermore, we identify many small-gap materials that are misclassified as metals in other databases. By providing accurate band gaps, the present database will be useful in screening materials in diverse applications.
Electroporation outperforms in vivo-jetPEI for intratumoral DNA-based reporter gene transfer
Authors: Jacobs Liesl , De Smidt Elien , Geukens Nick , Declerck Paul , Hollevoet Kevin
Published: November 2020

Intratumoral delivery of drug-encoding plasmid DNA (pDNA) enables localised in vivo expression of biological drugs, offering an attractive alternative to conventional protein treatment. However, this requires physical or chemical methods to enhance the low transfection efficiency of naked pDNA. Electroporation and complexation with the polycation in vivo-jetPEI are both evaluated in the clinic for intratumoral pDNA delivery, but lack head-to-head comparison. This study therefore compared both methods for intratumoral DNA-based reporter gene transfer in a subcutaneous mouse tumour model. Intratumoral electroporation resulted in strong reporter expression that was restricted to the tumour area and persisted for at least ten days. Intratumoral expression after injection of pDNA-jetPEI complexes was two to three logs lower, did not exceed the background in most mice, and lasted less than five days even with repeated dosing. Remarkably, reporter expression was primarily detected in the lungs, presumably due to leakage of pDNA-jetPEI complexes into the systemic circulation. In conclusion, electroporation enabled more efficient, prolonged and tumour-specific reporter expression compared to intratumoral injection of pDNA complexed with in vivo-jetPEI. These results favour the use of electroporation for intratumoral DNA-based gene transfer, and suggest further optimisation of pDNA-jetPEI complexes is needed to improve their efficacy and biosafety.
Prevalence and risk factors of primary sarcopenia in community-dwelling outpatient elderly: a cross-sectional study
Authors: Therakomen Visaratana , Petchlorlian Aisawan , Lakananurak Narisorn
Published: November 2020

No previous study has investigated the prevalence and risk factors for primary sarcopenia in outpatient setting. This study aims to evaluate the prevalence and factors associated with primary sarcopenia in outpatient elderly. Additionally, we compared the severity of sarcopenia based on the 2014 and 2019 Asian Working Group for Sarcopenia (AWGS) criteria. This cross-sectional study was performed in 330 subjects aged over 60 years in an outpatient setting. The muscle strength, muscle performance and muscle mass were assessed using the handheld dynamometer, 6-m gait speed, and bioelectrical impedance analysis, respectively. The prevalence of sarcopenia was 10% as per the 2014 and 2019 AWGS criteria. The development of sarcopenia was positively correlated with the age with an odds ratio (OR) of 6.87 [95% confidence interval (CI) 1.63–28.88] in the middle-old group (70–79 years), and 13.71 (95%CI 3.66–51.41; p = 0.009) in the very old group (≥ 80 years). Prefrailty and low physical activity were significantly associated with sarcopenia with an OR of 4.75 (95%CI 1.90—11.89) in prefrailty, 15.35 (95%CI 1.69–139.47) in the middle activity group, and 17.99 (95%CI 1.95–165.73) in the lowest activity group. In conclusion, primary sarcopenia was found in one-tenth of outpatient elderly. Age, prefrailty, and low activity were independent factors associated with sarcopenia.
Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
Authors: Dutta Noton K. , Tornheim Jeffrey A. , Fukutani Kiyoshi F. , Paradkar Mandar , Tiburcio Rafael T. , Kinikar Aarti , Valvi Chhaya , Kulkarni Vandana , Pradhan Neeta , Shivakumar Shri Vijay Bala Yogendra , Kagal Anju , Gupte Akshay , Gupte Nikhil , Mave Vidya , Gupta Amita , Andrade Bruno B. , Karakousis Petros C.
Published: November 2020

Pediatric tuberculosis (TB) remains a major global health problem. Improved pediatric diagnostics using readily available biosources are urgently needed. We used liquid chromatography-mass spectrometry to analyze plasma metabolite profiles of Indian children with active TB (n = 16) and age- and sex-matched, Mycobacterium tuberculosis-exposed but uninfected household contacts (n = 32). Metabolomic data were integrated with whole blood transcriptomic data for each participant at diagnosis and throughout treatment for drug-susceptible TB. A decision tree algorithm identified 3 metabolites that correctly identified TB status at distinct times during treatment. N-acetylneuraminate achieved an area under the receiver operating characteristic curve (AUC) of 0.66 at diagnosis. Quinolinate achieved an AUC of 0.77 after 1 month of treatment, and pyridoxate achieved an AUC of 0.87 after successful treatment completion. A set of 4 metabolites (gamma-glutamylalanine, gamma-glutamylglycine, glutamine, and pyridoxate) identified treatment response with an AUC of 0.86. Pathway enrichment analyses of these metabolites and corresponding transcriptional data correlated N-acetylneuraminate with immunoregulatory interactions between lymphoid and non-lymphoid cells, and correlated pyridoxate with p53-regulated metabolic genes and mitochondrial translation. Our findings shed new light on metabolic dysregulation in children with TB and pave the way for new diagnostic and treatment response markers in pediatric TB.
Discovery and comparative genomic analysis of elk circovirus (ElkCV), a novel circovirus species and the first reported from a cervid host
Authors: Fisher Mathew , Harrison Thomas M. R. , Nebroski Michelle , Kruczkiewicz Peter , Rothenburger Jamie L. , Ambagala Aruna , Macbeth Bryan , Lung Oliver
Published: November 2020

The complete genome sequence of a novel circovirus (elk circovirus (ElkCV) Banff/2019) was determined via high throughput sequencing of liver tissue from a euthanized Rocky Mountain elk (Cervus canadensis nelsoni) from Alberta, Canada. The genome is circular and 1,787 nucleotides long, with two major ORFs encoding predicted proteins. Comparative genomic analysis to 4,164 publicly available complete and near complete circovirus genomes showed that ElkCV shares approximately 65% pairwise genome-wide nucleotide identity with the most closely related circovirus species, porcine circoviruses (PCV) 1 and 2 and bat-associated circovirus (BatACV) 11. ElkCV features a stem-loop within the origin of replication region characteristic of circoviruses. However, it differs from those found in PCV1, PCV2 and BatACV11 since it has a longer stem and contains hexamer repeats that overlap the stem in opposing orientations. Interestingly, stem-loop structures of similar length featuring repeats in a similar position and orientation are also seen in some avian circoviruses. Based on the demarcation threshold established by the International Committee on Taxonomy of Viruses (ICTV) for members of Circoviridae (80% pairwise genome-wide nucleotide identity), ElkCV represents a novel species and is the first complete circovirus genome reported from a cervid host.
Enhanced risk of cancer in companion animals as a response to the longevity
Authors: Tanaka Moeko , Yamaguchi Sachi , Iwasa Yoh
Published: November 2020

Cancer is caused by the lifetime accumulation of multiple somatic deformations of the genome and epigenome. At a very low rate, mistakes occur during genomic replication (e.g., mutations or modified epigenetic marks). Long-lived species, such as elephants, are suggested to have evolved mechanisms to slow down the cancer progression. Recently, the life span of companion dogs has increased considerably than before, owing to the improvement of their environment, which has led to an increase in the fraction of companion dogs developing cancer. These findings suggest that short-term responses of cancer risk to longevity differ from long-term responses. In this study, to clarify the situation, we used a simple multi-step model for cancer. The rates of events leading to malignant cancer are assumed to be proportional to those of genomic replication error. Perfect removal of replication error requires a large cost, resulting in the evolution of a positive rate of genomic replication error. The analysis of the model revealed: that, when the environment suddenly becomes benign, the relative importance of cancer enhances, although the age-dependent cancer risk remains unchanged. However, in the long run, the genomic error rate evolves to become smaller and mitigates the cancer risk.
A simple PCR-based method for the rapid and accurate identification of spider mites (Tetranychidae) on cassava
Authors: Ovalle Tatiana M. , Vásquez-Ordóñez Aymer Andrés , Jimenez Jenyfer , Parsa Soroush , Cuellar Wilmer J. , Becerra Lopez-Lavalle Luis A.
Published: November 2020

The morphological identification of mites entails great challenges. Characteristics such as dorsal setae and aedeagus are widely used, but they show variations between populations, and the technique is time consuming and demands specialized taxonomic expertise that is difficult to access. A successful alternative has been to exploit a region of the mitochondrial cytochrome oxidase I (COI) gene to classify specimens to the species level. We analyzed the COI sequences of four mite species associated with cassava and classified them definitively by detailed morphological examinations. We then developed an identification kit based on the restriction fragment length polymorphism–polymerase chain reaction of subunit I of the COI gene focused on the three restriction enzymes AseI, MboII, and ApoI. This set of enzymes permitted the simple, accurate identification of Mononychellus caribbeanae, M. tanajoa, M. mcgregori, and Tetranychus urticae, rapidly and with few resources. This kit could be a vital tool for the surveillance and monitoring of mite pests in cassava crop protection programs in Africa, Asia, and Latin America.
Quantitative measures of vortex veins in the posterior pole in eyes with pachychoroid spectrum diseases
Authors: Matsumoto Hidetaka , Hoshino Junki , Arai Yosuke , Mukai Ryo , Nakamura Kosuke , Kikuchi Yuka , Kishi Shoji , Akiyama Hideo
Published: November 2020

Pachychoroid spectrum diseases have attracted increasing attention, though their pathophysiology has yet to be fully elucidated. In this study, we assessed the vascular diameters of vortex veins in pachychoroid spectrum diseases such as central serous chorioretinopathy (CSC), pachychoroid neovasculopathy without polypoidal lesions (PNV), and pachychoroid neovasculopathy with polypoidal lesions (polypoidal choroidal vasculopathy: PCV). In a retrospective case series of 94 eyes with CSC, 60 eyes with PNV and 57 with PCV, we binarized en face optical coherence tomography (OCT) images of choroidal vortex veins and analyzed the mean diameter of vortex veins. The presence of anastomosis between the superior and inferior vortex veins and central choroidal thickness (CCT) were also evaluated using OCT images. CSC showed significantly larger mean diameter of vortex veins than PCV (P < 0.05). Anastomosis between superior and inferior vortex veins was observed in over 90% of eyes with each pachychoroid spectrum disease. The patients with CSC were the youngest, followed by PNV patients, and then patients with PCV. The largest CCT values were observed in CSC eyes, followed by PNV eyes, and then PCV eyes. CCT correlated with the mean diameter of vortex veins (rs = 0.51, P < 0.01). These findings suggest that congestion of vortex veins might show gradual amelioration corresponding to the development of anastomosis between the superior and inferior vortex veins during the course of progression of pachychoroid spectrum diseases. Moreover, the mean diameter of vortex veins can be used as a parameter indicating choroidal congestion.
Widespread elevated iridium in Upper Triassic–Lower Jurassic strata of the Newark Supergroup: implications for use as an extinction marker
Authors: Tanner Lawrence H. , Kyte Frank T. , Puffer John H.
Published: November 2020

Anomalous levels of iridium in sedimentary strata are associated with mass extinction events caused by impact events. In the case of the end-Triassic extinction event, the anomalies as well as the extinctions are linked to the eruption of the Central Atlantic Magmatic Province (CAMP) flood basalts. We report new data on concentrations of iridium in continental strata of the Fundy, Deerfield, Hartford and Newark basins, both above and below the oldest CAMP flows in these basins, that demonstrate that these anomalies are more common than previously known. We conclude that the enrichments were at least in some instances likely derived locally by concentration due to leaching directly from the lavas into sediments proximal to the CAMP flows due to post-eruptive hydrothermal activity. In other instances, the enrichments likely record the global fallout of aerosols and/or ash particles during the eruptions of the CAMP basalts. The common association of the highest levels of enrichment with organic matter suggests either redox control or stabilization by formation of organometallic complexes following post-eruptive redistribution. These findings demonstrate the importance of considering the distribution and magnitude of iridium anomalies in considering the source of the iridium and possible extinction mechanisms.
Human mesenchymal stromal/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats
Authors: Menezes Karla , Rosa Barbara Gomes , Freitas Catarina , da Cruz Aline Silva , de Siqueira Santos Raphael , Nascimento Marcos Assis , Alves Daiana Vieira Lopes , Bonamino Martin , Rossi Maria Isabel , Borojevic Radovan , Coelho-Sampaio Tatiana
Published: November 2020

Angiogenesis is considered to mediate the beneficial effects of mesenchymal cell therapy in spinal cord injury. After a moderate balloon-compression injury in rats, injections of either human adipose tissue-derived stromal/stem cells (hADSCs) or their conditioned culture media (CM-hADSC) elicited angiogenesis around the lesion site. Both therapies increased vascular density, but the presence of hADSCs in the tissue was required for the full maturation of new blood vessels. Only animals that received hADSC significantly improved their open field locomotion, assessed by the BBB score. Animals that received CM-hADSC only, presented haemorrhagic areas and lack pericytes. Proteomic analyses of human angiogenesis-related factors produced by hADSCs showed that both pro- and anti-angiogenic factors were produced by hADSCs in vitro, but only those related to vessel maturation were detectable in vivo. hADSCs produced PDGF-AA only after insertion into the injured spinal cord. hADSCs attracted resident pericytes expressing NG2, α-SMA, PDGF-Rβ and nestin to the lesion, potentially contributing to blood vessel maturation. We conclude that the presence of hADSCs in the injured spinal cord is essential for tissue repair.
Using static method to measure tolmetin solubility at different pressures and temperatures in supercritical carbon dioxide
Authors: Pishnamazi Mahboubeh , Zabihi Samyar , Sarafzadeh Pegah , Borousan Fatemeh , Marjani Azam , Pelalak Rasool , Shirazian Saeed
Published: November 2020

Tolmetin is a non-steroidal anti-inflammatory drug being used to decrease the level of hormones which are the reasons for pain, swelling, tiredness, and stiffness for osteoarthritis and rheumatoid arthritis cases. We evaluated its solubility in supercritical carbon dioxide (SC-CO2) with the aim of drug nanonization, considering temperature and pressure variations between 120 and 400 bar and 308–338 K, in the experiments. In this way, a PVT solubility cell based on static solubility approach coupled with a simple gravimetric procedure was utilized to evaluate the solubility of tolmetin. The solubility values between 5.00 × 10−5and 2.59 × 10−3 mol fraction were obtained for tolmetin depending on the pressure and temperature of the cell. The measured data demonstrated a direct correlation between pressure and solubility of tolmetin, while the effect of temperature was a dual effect depending on the crossover pressure (160 bar). The calculated solubility data were modeled using several semi-empirical correlations, and the fitting parameters were calculated using the experimental data via appropriate optimization method. The correlated solubility data revealed that the KJ model was the most accurate one with an average absolute relative deviation percent (AARD%) of 6.9. Moreover, the carried out self-consistency analysis utilizing these correlations illustrated great potential of these models to extrapolate the solubility of tolmetin beyond the measured conditions.
Effects of top electrode material in hafnium-oxide-based memristive systems on highly-doped Si
Authors: Saylan Sueda , Aldosari Haila M. , Humood Khaled , Abi Jaoude Maguy , Ravaux Florent , Mohammad Baker
Published: November 2020

This work provides useful insights into the development of HfO2-based memristive systems with a p-type silicon bottom electrode that are compatible with the complementary metal–oxide–semiconductor technology. The results obtained reveal the importance of the top electrode selection to achieve unique device characteristics. The Ag/HfO2/Si devices have exhibited a larger memory window and self-compliance characteristics. On the other hand, the Au/HfO2/Si devices have displayed substantial cycle-to-cycle variation in the ON-state conductance. These device characteristics can be used as an indicator for the design of resistive-switching devices in various scenes such as, memory, security, and sensing. The current–voltage (I–V) characteristics of Ag/HfO2/Si and Au/HfO2/Si devices under positive and negative bias conditions have provided valuable information on the ON and OFF states of the devices and the underlying resistive switching mechanisms. Repeatable, low-power, and forming-free bipolar resistive switching is obtained with both device structures, with the Au/HfO2/Si devices displaying a poorer device-to-device reproducibility. Furthermore, the Au/HfO2/Si devices have exhibited N-type negative differential resistance (NDR), suggesting Joule-heating activated migration of oxygen vacancies to be responsible for the SET process in the unstable unipolar mode.
A novel cryo-embedding method for in-depth analysis of craniofacial mini pig bone specimens
Authors: Ticha Pavla , Pilawski Igor , Yuan Xue , Pan Jie , Tulu Ustun S. , Coyac Benjamin R. , Hoffmann Waldemar , Helms Jill A.
Published: November 2020

The disconnect between preclinical and clinical results underscores the imperative for establishing good animal models, then gleaning all available data on efficacy, safety, and potential toxicities associated with a device or drug. Mini pigs are a commonly used animal model for testing orthopedic and dental devices because their skeletons are large enough to accommodate human-sized implants. The challenge comes with the analyses of their hard tissues: current methods are time-consuming, destructive, and largely limited to histological observations made from the analysis of very few tissue sections. We developed and employed cryo-based methods that preserved the microarchitecture and the cellular/molecular integrity of mini pig hard tissues, then demonstrated that the results of these histological, histochemical, immunohistochemical, and dynamic histomorphometric analyses e.g., mineral apposition rates were comparable with similar data from preclinical rodent models. Thus, the ability to assess static and dynamic bone states increases the translational value of mini pig and other large animal model studies. In sum, this method represents logical means to minimize the number of animals in a study while simultaneously maximizing the amount of information collected from each specimen.
Multi-beam X-ray ptychography for high-throughput coherent diffraction imaging
Authors: Yao Yudong , Jiang Yi , Klug Jeffrey A. , Wojcik Michael , Maxey Evan R. , Sirica Nicholas S. , Roehrig Christian , Cai Zhonghou , Vogt Stefan , Lai Barry , Deng Junjing
Published: November 2020

X-ray ptychography is a rapidly developing coherent diffraction imaging technique that provides nanoscale resolution on extended field-of-view. However, the requirement of coherence and the scanning mechanism limit the throughput of ptychographic imaging. In this paper, we propose X-ray ptychography using multiple illuminations instead of single illumination in conventional ptychography. Multiple locations of the sample are simultaneously imaged by spatially separated X-ray beams, therefore, the obtained field-of-view in one scan can be enlarged by a factor equal to the number of illuminations. We have demonstrated this technique experimentally using two X-ray beams focused by a house-made Fresnel zone plate array. Two areas of the object and corresponding double illuminations were successfully reconstructed from diffraction patterns acquired in one scan, with image quality similar with those obtained by conventional single-beam ptychography in sequence. Multi-beam ptychography approach increases the imaging speed, providing an efficient way for high-resolution imaging of large extended specimens.
Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards
Authors: Nissen Karolina , Krambrich Janina , Akaberi Dario , Hoffman Tove , Ling Jiaxin , Lundkvist Åke , Svensson Lennart , Salaneck Erik
Published: November 2020

Evidence suggests that SARS-CoV-2, as well as other coronaviruses, can be dispersed and potentially transmitted by aerosols directly or via ventilation systems. We therefore investigated ventilation openings in one COVID-19 ward and central ducts that expel indoor air from three COVID-19 wards at Uppsala University Hospital, Sweden, during April and May 2020. Swab samples were taken from individual ceiling ventilation openings and surfaces in central ducts. Samples were subsequently subjected to rRT-PCR targeting the N and E genes of SARS-CoV-2. Central ventilation HEPA filters, located several stories above the wards, were removed and portions analyzed in the same manner. In two subsequent samplings, SARS-CoV-2 N and E genes were detected in seven and four out of 19 room vents, respectively. Central ventilation HEPA exhaust filters from the ward were found positive for both genes in three samples. Corresponding filters from two other, adjacent COVID-19 wards were also found positive. Infective ability of the samples was assessed by inoculation of susceptible cell cultures but could not be determined in these experiments. Detection of SARS-CoV-2 in central ventilation systems, distant from patient areas, indicate that virus can be transported long distances and that droplet transmission alone cannot reasonably explain this, especially considering the relatively low air change rates in these wards. Airborne transmission of SARS-CoV-2 must be taken into consideration for preventive measures.