bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of Volatile‐Induced Melting in the Northeast Asian Upper Mantle
Authors: Sun Yizhuo , Hier‐Majumder Saswata , Tauzin Benoit , Walter Michael , Ballmer Maxim , Xu Yigang , Kim Seongryong
Published: October 2021

A seismic low velocity layer (LVL) above the mantle transition zone (MTZ), often thought to be caused by volatile‐induced melting, can significantly modulate planetary volatile cycles. In this work, we show that an LVL observed beneath northeast Asia is characterized by small, 0.8 0.5 vol%, average degrees of partial melting. Seismically derived P‐T conditions of the LVL indicate that slab‐derived , possibly combined with small amounts of O, is necessary to induce melting. Modeling the reactive infiltration instability of the melt in a stationary mantle above a stalled slab, we demonstrate that the volatile‐rich melt slowly rises above the stalled slab in the MTZ, with percolation velocities of 200–500 m/yr. The melt remains stable within the LVL for this geologically significant period of time, potentially transferring up to 52 Mt/yr of from the subducting slab to the mantle for an LVL similar in areal extent () to the northeast Asian LVL. Reaction between the melt channels and the LVL mantle precipitates up to 200 ppmw solid C in localized zones. Using the inferred small melt volume fraction to model trace element abundances and isotopic signatures, we show that interaction between this melt and the surrounding mantle can over the long‐term produce rocks bearing a HIMU like geochemical signature.
Canine hyperactivity, impulsivity, and inattention share similar demographic risk factors and behavioural comorbidities with human ADHD
Authors: Sulkama Sini , Puurunen Jenni , Salonen Milla , Mikkola Salla , Hakanen Emma , Araujo César , Lohi Hannes
Published: October 2021

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder impairing the quality of life of the affected individuals. The domestic dog can spontaneously manifest high hyperactivity/impulsivity and inattention which are components of human ADHD. Therefore, a better understanding of demographic, environmental and behavioural factors influencing canine hyperactivity/impulsivity and inattention could benefit both humans and dogs. We collected comprehensive behavioural survey data from over 11,000 Finnish pet dogs and quantified their level of hyperactivity/impulsivity and inattention. We performed generalised linear model analyses to identify factors associated with these behavioural traits. Our results indicated that high levels of hyperactivity/impulsivity and inattention were more common in dogs that are young, male and spend more time alone at home. Additionally, we showed several breed differences suggesting a substantial genetic basis for these traits. Furthermore, hyperactivity/impulsivity and inattention had strong comorbidities with compulsive behaviour, aggressiveness and fearfulness. Multiple of these associations have also been identified in humans, strengthening the role of the dog as an animal model for ADHD.
FKBP51 promotes invasion and migration by increasing the autophagic degradation of TIMP3 in clear cell renal cell carcinoma
Authors: Mao Shaowei , Zhang Di , Chen Luan , Tan Jie , Chu Yunpeng , Huang Sijia , Zhou Wenqi , Qin Hengwei , Xia Qinghua , Zhao Yueran , Li Rongxiu , Qin Shengying , Wei Muyun
Published: October 2021

The occurrence of metastasis is a serious risk for renal cell carcinoma (RCC) patients. In order to develop novel therapeutic approaches to control the progression of metastatic RCC, it is of urgent need to understand the molecular mechanisms underlying RCC metastasis and identify prognostic markers of metastatic risk. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been known to be closely associated with extracellular matrix (ECM) turnover, which plays a highly active role in tumor metastasis. Recent studies have shown that immunophilin FK-506-binding protein 51 (FKBP51) may be important for the regulation of ECM function, and exert effects on the invasion and migration of tumor cells. However, the mechanisms underlying these activities remain unclear. The present study detected the role of FKBP51 in clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, and found that FKBP51 significantly promotes ccRCC invasion and migration by binding with the TIMP3, connecting TIMP3 with Beclin1 complex and increasing autophagic degradation of TIMP3. Given the important roles that TIMPs/MMPs play in ECM regulation and remodeling, our findings will provide new perspective for future investigation of the regulation of metastasis of kidney cancer and other types of cancer.
Sclareol and linalyl acetate are produced by glandular trichomes through the MEP pathway
Authors: Chalvin Camille , Drevensek Stéphanie , Gilard Françoise , Mauve Caroline , Chollet Christel , Morin Halima , Nicol Edith , Héripré Eva , Kriegshauser Lucie , Gakière Bertrand , Dron Michel , Bendahmane Abdelhafid , Boualem Adnane
Published: October 2021

Sclareol, an antifungal specialized metabolite produced by clary sage, Salvia sclarea, is the starting plant natural molecule used for the hemisynthesis of the perfume ingredient ambroxide. Sclareol is mainly produced in clary sage flower calyces; however, the cellular localization of the sclareol biosynthesis remains unknown. To elucidate the site of sclareol biosynthesis, we analyzed its spatial distribution in the clary sage calyx epidermis using laser desorption/ionization mass spectrometry imaging (LDI–FTICR-MSI) and investigated the expression profile of sclareol biosynthesis genes in isolated glandular trichomes (GTs). We showed that sclareol specifically accumulates in GTs’ gland cells in which sclareol biosynthesis genes are strongly expressed. We next isolated a glabrous beardless mutant and demonstrate that more than 90% of the sclareol is produced by the large capitate GTs. Feeding experiments, using 1-13C-glucose, and specific enzyme inhibitors further revealed that the methylerythritol-phosphate (MEP) biosynthetic pathway is the main source of isopentenyl diphosphate (IPP) precursor used for the biosynthesis of sclareol. Our findings demonstrate that sclareol is an MEP-derived diterpene produced by large capitate GTs in clary sage emphasing the role of GTs as biofactories dedicated to the production of specialized metabolites.
Frequent germplasm exchanges drive the high genetic diversity of Chinese-cultivated common apricot germplasm
Authors: Zhang Qiuping , Zhang Diyang , Yu Kang , Ji Jingjing , Liu Ning , Zhang Yuping , Xu Ming , Zhang Yu-Jun , Ma Xiaoxue , Liu Shuo , Sun Wei-Hong , Yu Xia , Hu Wenqi , Lan Si-Ren , Liu Zhong-Jian , Liu Weisheng
Published: October 2021

The genetic diversity of germplasm is critical for exploring genetic and phenotypic resources and has important implications for crop-breeding sustainability and improvement. However, little is known about the factors that shape and maintain genetic diversity. Here, we assembled a high-quality chromosome-level reference of the Chinese common apricot ‘Yinxiangbai’, and we resequenced 180 apricot accessions that cover four major ecogeographical groups in China and other accessions from occidental countries. We concluded that Chinese-cultivated common apricot germplasms possessed much higher genetic diversity than those cultivated in Western countries. We also detected seven migration events among different apricot groups, where 27% of the genome was identified as being introgressed. Remarkably, we demonstrated that these introgressed regions drove the current high level of germplasm diversity in Chinese-cultivated common apricots by introducing different genes related to distinct phenotypes from different cultivated groups. Our results highlight the consideration that introgressed regions may provide an important reservoir of genetic resources that can be used to sustain modern breeding programs.
Genomic and transcriptomic analyses of Citrus sinensis varieties provide insights into Valencia orange fruit mastication trait formation
Authors: Feng Guizhi , Ai Xiu , Yi Hualin , Guo Wenwu , Wu Juxun
Published: October 2021

Valencia orange (Citrus sinensis Osbeck) (VO) is a type of late-ripening sweet orange whose ripening occurs 4 to 5 months later than that of the mid-ripening common sweet orange (CO). Notably, the mastication trait of VO fruit is inferior to that of CO fruit. To date, how inferior pulp mastication trait forms in VO has not been determined. In this study, 13 VO varieties and 12 CO varieties were subjected to whole-genome resequencing. A total of 2.98 million SNPs were identified from 25 varieties, and a SNP molecular marker was developed to distinguish VO and CO. Moreover, 144 and 141 genes identified by selective sweep analysis were selected during VO and CO evolution, respectively. Based on gene functional enrichment analysis, most of the selected VO genes were related to the stress response and lignin biosynthesis. Simultaneously, we comparatively analyzed the transcriptome profiles of peel and pulp tissues among three VO varieties and three CO varieties, and the results demonstrated differences in lignin biosynthesis between VO and CO fruits. Furthermore, coexpression network analysis was performed to identify hub genes of lignin-related and variety-specific networks, which included CsERF74, CsNAC25, CsHSFB3, CsSPL4/13, etc. Overall, this study provides important insights into the mastication trait formation of Valencia orange fruit.
Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle
Authors: Liu Xiuxiu , Pu Wenjuan , He Lingjuan , Li Yan , Zhao Huan , Li Yi , Liu Kuo , Huang Xiuzhen , Weng Wendong , Wang Qing-Dong , Shen Linghong , Zhong Tao , Sun Kun , Ardehali Reza , He Ben , Zhou Bin
Published: October 2021

Cardiac regeneration involves the generation of new cardiomyocytes from cycling cardiomyocytes. Understanding cell-cycle activity of pre-existing cardiomyocytes provides valuable information to heart repair and regeneration. However, the anatomical locations and in situ dynamics of cycling cardiomyocytes remain unclear. Here we develop a genetic approach for a temporally seamless recording of cardiomyocyte-specific cell-cycle activity in vivo. We find that the majority of cycling cardiomyocytes are positioned in the subendocardial muscle of the left ventricle, especially in the papillary muscles. Clonal analysis revealed that a subset of cycling cardiomyocytes have undergone cell division. Myocardial infarction and cardiac pressure overload induce regional patterns of cycling cardiomyocytes. Mechanistically, cardiomyocyte cell cycle activity requires the Hippo pathway effector YAP. These genetic fate-mapping studies advance our basic understanding of cardiomyocyte cell cycle activity and generation in cardiac homeostasis, repair, and regeneration.
Neurofibromin 1 in mushroom body neurons mediates circadian wake drive through activating cAMP–PKA signaling
Authors: Machado Almeida Pedro , Lago Solis Blanca , Stickley Luca , Feidler Alexis , Nagoshi Emi
Published: October 2021

Various behavioral and cognitive states exhibit circadian variations in animals across phyla including Drosophila melanogaster, in which only ~0.1% of the brain’s neurons contain circadian clocks. Clock neurons transmit the timing information to a plethora of non-clock neurons via poorly understood mechanisms. Here, we address the molecular underpinning of this phenomenon by profiling circadian gene expression in non-clock neurons that constitute the mushroom body, the center of associative learning and sleep regulation. We show that circadian clocks drive rhythmic expression of hundreds of genes in mushroom body neurons, including the Neurofibromin 1 (Nf1) tumor suppressor gene and Pka-C1. Circadian clocks also drive calcium rhythms in mushroom body neurons via NF1-cAMP/PKA-C1 signaling, eliciting higher mushroom body activity during the day than at night, thereby promoting daytime wakefulness. These findings reveal the pervasive, non-cell-autonomous circadian regulation of gene expression in the brain and its role in sleep.
A scalable, secure, and interoperable platform for deep data-driven health management
Authors: Bahmani Amir , Alavi Arash , Buergel Thore , Upadhyayula Sushil , Wang Qiwen , Ananthakrishnan Srinath Krishna , Alavi Amir , Celis Diego , Gillespie Dan , Young Gregory , Xing Ziye , Nguyen Minh Hoang Huynh , Haque Audrey , Mathur Ankit , Payne Josh , Mazaheri Ghazal , Li Jason Kenichi , Kotipalli Pramod , Liao Lisa , Bhasin Rajat , Cha Kexin , Rolnik Benjamin , Celli Alessandra , Dagan-Rosenfeld Orit , Higgs Emily , Zhou Wenyu , Berry Camille Lauren , Van Winkle Katherine Grace , Contrepois Kévin , Ray Utsab , Bettinger Keith , Datta Somalee , Li Xiao , Snyder Michael P.
Published: October 2021

The large amount of biomedical data derived from wearable sensors, electronic health records, and molecular profiling (e.g., genomics data) is rapidly transforming our healthcare systems. The increasing scale and scope of biomedical data not only is generating enormous opportunities for improving health outcomes but also raises new challenges ranging from data acquisition and storage to data analysis and utilization. To meet these challenges, we developed the Personal Health Dashboard (PHD), which utilizes state-of-the-art security and scalability technologies to provide an end-to-end solution for big biomedical data analytics. The PHD platform is an open-source software framework that can be easily configured and deployed to any big data health project to store, organize, and process complex biomedical data sets, support real-time data analysis at both the individual level and the cohort level, and ensure participant privacy at every step. In addition to presenting the system, we illustrate the use of the PHD framework for large-scale applications in emerging multi-omics disease studies, such as collecting and visualization of diverse data types (wearable, clinical, omics) at a personal level, investigation of insulin resistance, and an infrastructure for the detection of presymptomatic COVID-19.
CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
Authors: Kim Myung-Chul , Borcherding Nicholas , Ahmed Kawther K. , Voigt Andrew P. , Vishwakarma Ajaykumar , Kolb Ryan , Kluz Paige N. , Pandey Gaurav , De Umasankar , Drashansky Theodore , Helm Eric Y. , Zhang Xin , Gibson-Corley Katherine N. , Klesney-Tait Julia , Zhu Yuwen , Lu Jinglu , Lu Jinsong , Huang Xian , Xiang Hongrui , Cheng Jinke , Wang Dongyang , Wang Zheng , Tang Jian , Hu Jiajia , Wang Zhengting , Liu Hua , Li Mingjia , Zhuang Haoyang , Avram Dorina , Zhou Daohong , Bacher Rhonda , Zheng Song Guo , Wu Xuefeng , Zakharia Yousef , Zhang Weizhou
Published: October 2021

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD177 reduces the suppressive activity of Treg cells in vitro, while Treg-specific deletion of Cd177 leads to decreased tumor growth and reduced TI Treg frequency in mice. Our results thus uncover a functional CD177+ TI Treg population that may serve as a target for TI Treg-specific immunotherapy.
Budget constrained machine learning for early prediction of adverse outcomes for COVID-19 patients
Authors: Nguyen Sam , Chan Ryan , Cadena Jose , Soper Braden , Kiszka Paul , Womack Lucas , Work Mark , Duggan Joan M. , Haller Steven T. , Hanrahan Jennifer A. , Kennedy David J. , Mukundan Deepa , Ray Priyadip
Published: October 2021

The combination of machine learning (ML) and electronic health records (EHR) data may be able to improve outcomes of hospitalized COVID-19 patients through improved risk stratification and patient outcome prediction. However, in resource constrained environments the clinical utility of such data-driven predictive tools may be limited by the cost or unavailability of certain laboratory tests. We leveraged EHR data to develop an ML-based tool for predicting adverse outcomes that optimizes clinical utility under a given cost structure. We further gained insights into the decision-making process of the ML models through an explainable AI tool. This cohort study was performed using deidentified EHR data from COVID-19 patients from ProMedica Health System in northwest Ohio and southeastern Michigan. We tested the performance of various ML approaches for predicting either increasing ventilatory support or mortality. We performed post hoc analysis to obtain optimal feature sets under various budget constraints. We demonstrate that it is possible to achieve a significant reduction in cost at the expense of a small reduction in predictive performance. For example, when predicting ventilation, it is possible to achieve a 43% reduction in cost with only a 3% reduction in performance. Similarly, when predicting mortality, it is possible to achieve a 50% reduction in cost with only a 1% reduction in performance. This study presents a quick, accurate, and cost-effective method to evaluate risk of deterioration for patients with SARS-CoV-2 infection at the time of clinical evaluation.
Size-induced twinning in InSb semiconductor during room temperature deformation
Authors: Mignerot Florent , Kedjar Bouzid , Bahsoun Hadi , Thilly Ludovic
Published: October 2021

Room-temperature deformation mechanism of InSb micro-pillars has been investigated via a multi-scale experimental approach, where micro-pillars of 2 µm and 5 µm in diameter were first fabricated by focused ion beam (FIB) milling and in situ deformed in the FIB-SEM by micro-compression using a nano-indenter equipped with a flat tip. Strain rate jumps have been performed to determine the strain rate sensitivity coefficient and the related activation volume. The activation volume is found to be of the order of 3–5 b3, considering that plasticity is mediated by Shockley partial dislocations. Transmission electron microscopy (TEM) thin foils were extracted from deformed micro-pillars via the FIB lift-out technique: TEM analysis reveals the presence of nano-twins as major mechanism of plastic deformation, involving Shockley partial dislocations. The presence of twins was never reported in previous studies on the plasticity of bulk InSb: this deformation mechanism is discussed in the context of the plasticity of small-scale samples.
In silico identification of variations in microRNAs with a potential impact on dairy traits using whole ruminant genome SNP datasets
Authors: Bourdon Céline , Boussaha Mekki , Bardou Philippe , Sanchez Marie-Pierre , Le Guillou Sandrine , Tribout Thierry , Larroque Hélène , Boichard Didier , Rupp Rachel , Le Provost Fabienne , Tosser-Klopp Gwenola
Published: October 2021

MicroRNAs are small noncoding RNAs that have important roles in the lactation process and milk biosynthesis. Some polymorphisms have been studied in various livestock species from the perspective of pathology or production traits. To target variants that could be the causal variants of dairy traits, genetic variants of microRNAs expressed in the mammary gland or present in milk and localized in dairy quantitative trait loci (QTLs) were investigated in bovine, caprine, and ovine species. In this study, a total of 59,124 (out of 28 millions), 13,427 (out of 87 millions), and 4761 (out of 38 millions) genetic variants in microRNAs expressed in the mammary gland or present in milk were identified in bovine, caprine, and ovine species, respectively. A total of 4679 of these detected bovine genetic variants are located in dairy QTLs. In caprine species, 127 genetic variants are localized in dairy QTLs. In ovine species, no genetic variant was identified in dairy QTLs. This study leads to the detection of microRNA genetic variants of interest in the context of dairy production, taking advantage of whole genome data to identify microRNA genetic variants expressed in the mammary gland and localized in dairy QTLs.
Critically coupled Fabry–Perot cavity with high signal contrast for refractive index sensing
Authors: Park Gyeong Cheol , Park Kwangwook
Published: October 2021

Perfect absorption at a resonance wavelength and extremely low absorption at the wavelength range of off-resonance in a one-port optical cavity is required for refractive index (RI) sensing with high signal contrast. Here, we propose and analyze an absorption-enhanced Fabry–Perot (MAFP) cavity based on a critical coupling condition in a near-infrared wavelength range. For a one-port cavity, a thick bottom Au is used as a mirror and an absorber. To achieve the critical coupling condition, a top dielectric metasurface is employed and tailored to balance the radiation coupling and the absorption coupling rates, and the one-port cavity is theoretically analyzed using temporal coupled-mode theory. We investigate two types of MAFP structures for gas and liquid. The gas MAFP cavity shows a sensitivity of ~ 1388 nm/RIU and a full-width at half-maximum of less than 0.7 nm. This MAFP cavity resolves the RI change of 5 × 10−4 with a reflectance signal margin of 50% and achieves a signal contrast of ~ 100%. The liquid MAFP cavity shows a sensitivity of ~ 996 nm/RIU when RI of liquid changes from 1.30 to 1.38. With tailoring the period of the metasurface maintaining its thickness, a signal contrast of ~ 100% is achieved for each specific RI range.
Three-dimensional culture method enhances the therapeutic efficacies of tonsil-derived mesenchymal stem cells in murine chronic colitis model
Authors: Song Eun Mi , Joo Yang Hee , Choe A. Reum , Park Yehyun , Tae Chung Hyun , Hong Ji Teak , Moon Chang Mo , Kim Seong-Eun , Jung Hye-Kyung , Shim Ki-Nam , Cho Kyung-Ah , Jo Inho , Jung Sung-Ae
Published: October 2021

Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-β, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P < 0.05). At days 18 and 30 after inducing chronic colitis, disease activity index scores were estimated to be significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001 and P < 0.001, respectively) and 2D-TMSC-treated groups (P = 0.022 and P = 0.004, respectively). Body weight loss was significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001) and 2D-TMSC-treated groups (P = 0.005). Colon length shortening was significantly recovered in the 3D-TMSC-treated group compared to that in the 2D-TMSC-treated group (P = 0.001). Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002). These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression.
Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans
Authors: Chenoweth Meghan J. , Cox Lisa Sanderson , Nollen Nikki L. , Ahluwalia Jasjit S. , Benowitz Neal L. , Lerman Caryn , Knight Jo , Tyndale Rachel F.
Published: October 2021

Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.
Acoustic emissions and kinematic instability of the osteoarthritic knee joint: comparison with radiographic findings
Authors: Nevalainen Mika T. , Veikkola Olli , Thevenot Jerome , Tiulpin Aleksei , Hirvasniemi Jukka , Niinimäki Jaakko , Saarakkala Simo S.
Published: October 2021

To evaluate the acoustic emissions (AE) and kinematic instability (KI) of the osteoarthritic (OA) knee joints, and to compare these signals to radiographic findings. Sixty-six female and 43 male participants aged 44–67 were recruited. On radiography, joint-space narrowing, osteophytes and Kellgren–Lawrence (KL) grade were evaluated. Based on radiography, 54 subjects (the study group) were diagnosed with radiographic OA (KL-grade ≥ 2) while the remaining 55 subjects (KL-grade < 2) formed the control group. AE and KI were recorded with a custom-made prototype and compared with radiographic findings using area-under-curve (AUC) and independent T-test. Predictive logistic regression models were constructed using leave-one-out cross validation. In females, the parameters reflecting consistency of the AE patterns during specific tasks, KI, BMI and age had a significant statistical difference between the OA and control groups (p = 0.001–0.036). The selected AE signals, KI, age and BMI were used to construct a predictive model for radiographic OA with AUC of 90.3% (95% CI 83.5–97.2%) which showed a statistical improvement of the reference model based on age and BMI, with AUC of 84.2% (95% CI 74.8–93.6%). In males, the predictive model failed to improve the reference model. AE and KI provide complementary information to detect radiographic knee OA in females.
Relationship between objective measures of hearing discrimination elicited by non-linguistic stimuli and speech perception in adults
Authors: Sohier Hugo , Bardy Fabrice , Ching Teresa Y. C.
Published: October 2021

Some people using hearing aids have difficulty discriminating between sounds even though the sounds are audible. As such, cochlear implants may provide greater benefits for speech perception. One method to identify people with auditory discrimination deficits is to measure discrimination thresholds using spectral ripple noise (SRN). Previous studies have shown that behavioral discrimination of SRN was associated with speech perception, and behavioral discrimination was also related to cortical responses to acoustic change or ACCs. We hypothesized that cortical ACCs could be directly related to speech perception. In this study, we investigated the relationship between subjective speech perception and objective ACC responses measured using SRNs. We tested 13 normal-hearing and 10 hearing-impaired adults using hearing aids. Our results showed that behavioral SRN discrimination was correlated with speech perception in quiet and in noise. Furthermore, cortical ACC responses to phase changes in the SRN were significantly correlated with speech perception. Audibility was a major predictor of discrimination and speech perception, but direct measures of auditory discrimination could contribute information about a listener’s sensitivity to acoustic cues that underpin speech perception. The findings lend support for potential application of measuring ACC responses to SRNs for identifying people who may benefit from cochlear implants.
Controlling the thermal conductivity of multilayer graphene by strain
Authors: Nakagawa Kaito , Satoh Kazuo , Murakami Shuichi , Takei Kuniharu , Akita Seiji , Arie Takayuki
Published: October 2021

Straintronics is a new concept to enhance electronic device performances by strain for next-generation information sensors and energy-saving technologies. The lattice deformation in graphene can modulate the thermal conductivity because phonons are the main heat carriers. However, the device fabrication process affects graphene’s heat transport properties due to its high stretchability. This study experimentally investigates the change in the thermal conductivity when biaxial tensile strain is applied to graphene. To eliminate non-strain factors, two mechanisms are considered: pressure-induced and electrostatic attraction–induced strain. Raman spectroscopy and atomic force microscopy precisely estimate the strain. The thermal conductivity of graphene decreases by approximately 70% with a strain of only 0.1%. Such thermal conductivity controllability paves the way for applying graphene as high-efficiency thermal switches and diodes in future thermal management devices.
Refinement of microbiota analysis of specimens from patients with respiratory infections using next-generation sequencing
Authors: Ikegami Hiroaki , Noguchi Shingo , Fukuda Kazumasa , Akata Kentaro , Yamasaki Kei , Kawanami Toshinori , Mukae Hiroshi , Yatera Kazuhiro
Published: October 2021

Next-generation sequencing (NGS) technologies have been applied in bacterial flora analysis. However, there is no standardized protocol, and the optimal clustering threshold for estimating bacterial species in respiratory infection specimens is unknown. This study was conducted to investigate the optimal threshold for clustering 16S ribosomal RNA gene sequences into operational taxonomic units (OTUs) by comparing the results of NGS technology with those of the Sanger method, which has a higher accuracy of sequence per single read than NGS technology. This study included 45 patients with pneumonia with aspiration risks and 35 patients with lung abscess. Compared to Sanger method, the concordance rates of NGS technology (clustered at 100%, 99%, and 97% homology) with the predominant phylotype were 78.8%, 71.3%, and 65.0%, respectively. With respect to the specimens dominated by the Streptococcus mitis group, containing several important causative agents of pneumonia, Bray Curtis dissimilarity revealed that the OTUs obtained at 100% clustering threshold (versus those obtained at 99% and 97% thresholds; medians of 0.35, 0.69, and 0.71, respectively) were more similar to those obtained by the Sanger method, with statistical significance (p < 0.05). Clustering with 100% sequence identity is necessary when analyzing the microbiota of respiratory infections using NGS technology.
Toward understanding of the methoxylated flavonoid biosynthesis pathway in Dracocephalum kotschyi Boiss
Authors: Poursalavati Abdonaser , Rashidi-Monfared Sajad , Ebrahimi Amin
Published: October 2021

Nowadays, with the development and advancement of next-generation sequencing technologies, a new path has been provided for transcriptomic studies. In this study, the transcriptome of Dracocephalum kotschyi Boiss., as an endemic and endangered plant which is contained a large amount of valuable secondary metabolites with antioxidant and anticancer properties, was sequenced. Then functional annotation and gene ontology analysis for 165,597 assembled transcripts were performed, most were associated with the metabolic pathways. This might be because there are various active biochemical pathways in this plant. Furthermore, after comprehensive transcript annotation, the putative genes involved in the main metabolic pathways of D. kotschyi were identified. Then, the biosynthetic pathway of its valuable methoxylated flavones was proposed. Finally, the accumulations of important methoxylated-flavone metabolites in three different tissues were quantified by HPLC. The relative expression of the genes involved in the proposed pathway was investigated by qRT-PCR, which indicated high expression levels in the bud tissue. The present results may lead to the design strategies to preserve the genetic diversity of endangered D. kotschyi plants and apply the new methods for engineering its valuable methoxylated-flavones pathway.
Label-free fiber-optic spherical tip biosensor to enable picomolar-level detection of CD44 protein
Authors: Bekmurzayeva Aliya , Ashikbayeva Zhannat , Myrkhiyeva Zhuldyz , Nugmanova Aigerim , Shaimerdenova Madina , Ayupova Takhmina , Tosi Daniele
Published: October 2021

Increased level of CD44 protein in serum is observed in several cancers and is associated with tumor burden and metastasis. Current clinically used detection methods of this protein are time-consuming and use labeled reagents for analysis. Therefore exploring new label-free and fast methods for its quantification including its detection in situ is of importance. This study reports the first optical fiber biosensor for CD44 protein detection, based on a spherical fiber optic tip device. The sensor is easily fabricated from an inexpensive material (single-mode fiber widely used in telecommunication) in a fast and robust manner through a CO2laser splicer. The fabricated sensor responded to refractive index change with a sensitivity of 95.76 dB/RIU. The spherical tip was further functionalized with anti-CD44 antibodies to develop a biosensor and each step of functionalization was verified by an atomic force microscope. The biosensor detected a target of interest with an achieved limit of detection of 17 pM with only minor signal change to two control proteins. Most importantly, concentrations tested in this work are very broad and are within the clinically relevant concentration range. Moreover, the configuration of the proposed biosensor allows its potential incorporation into an in situ system for quantitative detection of this biomarker in a clinical setting.
Radiologists can visually predict mortality risk based on the gestalt of chest radiographs comparable to a deep learning network
Authors: Weiss Jakob , Taron Jana , Jin Zexi , Mayrhofer Thomas , Aerts Hugo J. W. L. , Lu Michael T. , Hoffmann Udo
Published: October 2021

Deep learning convolutional neural network (CNN) can predict mortality from chest radiographs, yet, it is unknown whether radiologists can perform the same task. Here, we investigate whether radiologists can visually assess image gestalt (defined as deviation from an unremarkable chest radiograph associated with the likelihood of 6-year mortality) of a chest radiograph to predict 6-year mortality. The assessment was validated in an independent testing dataset and compared to the performance of a CNN developed for mortality prediction. Results are reported for the testing dataset only (n = 100; age 62.5 ± 5.2; male 55%, event rate 50%). The probability of 6-year mortality based on image gestalt had high accuracy (AUC: 0.68 (95% CI 0.58–0.78), similar to that of the CNN (AUC: 0.67 (95% CI 0.57–0.77); p = 0.90). Patients with high/very high image gestalt ratings were significantly more likely to die when compared to those rated as very low (p ≤ 0.04). Assignment to risk categories was not explained by patient characteristics or traditional risk factors and imaging findings (p ≥ 0.2). In conclusion, assessing image gestalt on chest radiographs by radiologists renders high prognostic accuracy for the probability of mortality, similar to that of a specifically trained CNN. Further studies are warranted to confirm this concept and to determine potential clinical benefits.
Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
Authors: Naik Abhijit S. , Wang Su Q. , Chowdhury Mahboob , Aqeel Jawad , O’Connor Christopher L. , Wiggins Jocelyn E. , Bitzer Markus , Wiggins Roger C.
Published: October 2021

Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic stress resulting in proteinuria and glomerulosclerosis, implying that GV increase could serve as a therapeutic target to prevent progression. In this report we examine how Angiotensin Converting Enzyme inhibition (ACEi), started before uninephrectomy can reduce compensatory GV increase in wild-type Fischer344 rats. An unbiased computer-assisted method was used for morphometric analysis. Urine Insulin-like growth factor-1 (IGF-1), the major diver of body and kidney growth, was used as a readout. In long-term (40-week) studies of uni-nephrectomized versus sham-nephrectomized rats a 2.2-fold increase in GV was associated with reduced podocyte density, increased proteinuria and glomerulosclerosis. Compensatory GV increase was largely prevented by ACEi started a week before but not after uni-nephrectomy with no measurable impact on long-term eGFR. Similarly, in short-term (14-day) studies, ACEi started a week before uni-nephrectomy reduced both GV increase and urine IGF-1 excretion. Thus, timing of ACEi in relation to uni-nephrectomy had significant impact on post-nephrectomy “compensatory” glomerular growth and outcomes that could potentially be used to improve kidney transplantation and live kidney donation outcomes.
Interferon-inducible protein, IFIX, has tumor-suppressive effects in oral squamous cell carcinoma
Authors: Wang Shan , Li Fang , Fan Haixia
Published: October 2021

IFIX, a newly discovered member of the interferon-inducible HIN-200 family, has been identified as a tumor suppressor in breast cancer; however, the involvement of IFIX in oral cancer are poorly understood. Here, we demonstrate a relationship between the level of IFIX expression and the invasive or migratory abilities of oral squamous cell carcinoma. Higher IFIX expression significantly correlated with clinicopathological parameters such as the histopathological grade of clinical samples. In vitro, IFIX overexpression suppressed the invasiveness of human tongue squamous cell carcinoma CAL-27 cells, and this inhibitory effect was mediated by stabilization of the cytoskeleton through various cytokeratins along with downregulation of paxillin, an intracellular adaptor protein that promotes tumor invasion. This inhibitory effect does not appear to affect the transformation of cancer stem-like cells in this cell culture model. Altogether, these data provide novel insights into the tumor-suppressive function of IFIX, namely, stabilization of the cancer cell cytoskeleton.
Revealing the influence of steric bulk on the triplet–triplet annihilation upconversion performance of conjugated polymers
Authors: O’shea Riley , Kendrick William J. , Gao Can , Owyong Tze Cin , White Jonathan M. , Ghiggino Kenneth P. , Wong Wallace W. H.
Published: October 2021

A series of poly(phenylene-vinylene)-based copolymers are synthesized using the Gilch method incorporating monomers with sterically bulky sidechains. The photochemical upconversion performance of these polymers as emitters are investigated using a palladium tetraphenyltetrabenzoporphyrin triplet sensitizer and MEH-PPV as reference. Increased incorporation of sterically bulky monomers leads to a reduction in the upconversion efficiency despite improved photoluminescence quantum yield. A phosphorescence quenching study indicates issues with the energy transfer process between the triplet sensitizer and the copolymers. The best performance with 0.18% upconversion quantum yield is obtained for the copolymer containing 10% monomer with bulky sidechains.
Exome-wide association study of levodopa-induced dyskinesia in Parkinson’s disease
Authors: König Eva , Nicoletti Alessandra , Pattaro Cristian , Annesi Grazia , Melotti Roberto , Gialluisi Alessandro , Schwienbacher Christine , Picard Anne , Blankenburg Hagen , Pichler Irene , Modugno Nicola , Ciullo Marina , Esposito Teresa , Domingues Francisco S. , Hicks Andrew A. , Zappia Mario , Pramstaller Peter P.
Published: October 2021

Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson’s disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component. We performed an hypothesis-free whole-exome sequencing (WES)-based screening of time-to-LID onset and attempted replication of previously published candidate gene studies. A WES association analysis was carried out in 134 PD patients in a meta-analytical framework. Replication was attempted in an independent study of 97 PD patients. Variants from previously reported candidate genes (OPRM1, COMT, BDNF) were also specifically examined. We significantly replicated, for the first time, an association of variant rs1799971 in the OPRM1 gene with time-to-LID onset. Furthermore, we identified two novel potentially functional variants, in the MAD2L2 (rs2233019) and MAP7 (rs35350783) genes, which were significantly associated at the discovery stage. In the replication study, the two variants showed direction-consistent effects but did not achieve the replication significance threshold. Our study provides the first WES results for time-to-LID onset, where we replicate association at OPRM1, and suggest new variants in MAD2L2 and MAP7 genes that are significant in discovery, but require larger datasets for replication. The results are being made publicly available to allow for independent external validation.
A novel thiol-labile cysteine protecting group for peptide synthesis based on a pyridazinedione (PD) scaffold
Authors: Spears Richard J. , McMahon Clíona , Shamsabadi Monika , Bahou Calise , Thanasi Ioanna A. , Rochet Léa N. C. , Forte Nafsika , Thoreau Fabien , Baker James R. , Chudasama Vijay
Published: October 2021

Herein we establish the compatibility of pyridazinediones (PDs) as thiol-labile cysteine protecting groups in solid phase peptide synthesis (SPPS).
Polydopamine-coated bimetallic ZIF derivatives as an air cathode for acidic Zn–air batteries with super-high potential
Authors: Chi Zhenzhen , Feng Yingying , Ma Yiru , Kong Dezhi , Yin Huixiang , Li Shaoxiang , Li Lin , Guo Ziyang , Wang Lei
Published: October 2021

NC@Co-HPNC is prepared and used as a bifunctional catalyst for acid–alkali dual-electrolyte-based Zn–air batteries that exhibit an ultra-high voltage of 2.1 V.
Reactive force fields for aqueous and interfacial magnesium carbonate formation
Authors: Zare Siavash , Qomi Mohammad Javad Abdolhosseini
Published: October 2021

Bicarbonate deprotonates to carbonate through a reaction with a hydroxide ion that structurally diffuses from the surface.
peri-Acenoacene molecules: tuning of the singlet and triplet excitation energies by modifying their radical character
Authors: Omist A. , Ricci G. , Derradji A. , Pérez-Jiménez A. J. , San-Fabián E. , Olivier Y. , Sancho-García J. C.
Published: October 2021

Can open-shell peri-acenoacenes act as OLED emitters? A study using FT-DFT, TD-DFT, SF-TD-DFT, CIS, CIS(D), SCS-CC2, SA-CASSCF, and SC-NEVPT2 methods.
Real-time observation of photoionization-induced water migration dynamics in 4-methylformanilide–water by picosecond time-resolved infrared spectroscopy and ab initio molecular dynamics simulations
Authors: Miyazaki Mitsuhiko , Kamiya Tairiku , Wohlgemuth Matthias , Chatterjee Kuntal , Mitrić Roland , Dopfer Otto , Fujii Masaaki
Published: October 2021

Picosecond time-resolved IR spectroscopy and ab initio MD simulation revealed that a methyl group causes acceleration of water migration dynamics by a factor two through increased vibrational density of states arising from its free internal rotation.
Evidence of gas-phase pyranose-to-furanose isomerization in protonated peptidoglycans
Authors: Guan Shanshan , Bythell Benjamin J.
Published: October 2021

Protonated peptidoglycans isomerize prior to glycosidic bond cleavage.
Recent progress in hydrogenation of esters on heterogeneous bimetallic catalysts
Authors: Strekalova Anna A. , Shesterkina Anastasiya A. , Kustov Leonid M.
Published: October 2021

The development and research of highly effective heterogeneous catalysts for the hydrogenation of esters, providing high activity and selectivity of the formation of the corresponding alcohols, is an urgent task of modern heterogeneous catalysis.
A Cu2+-selective colorimetric-fluorometric sensor based on an anthracenyl-modified oxacalix[4]arene
Authors: Wang Shao-Guang , Pang Yu , Xue Min , Yang Yong
Published: October 2021

An anthracenyl-modified oxacalix[4]arene with imine linkages exhibits highly selective and sensitive detection of Cu2+via drastic colour change and enhanced FL.
Host-dependent heterologous expression of berninamycin gene cluster leads to linear thiopeptide antibiotics
Authors: De Bidhan Chandra , Zhang Wenjun , Zhang Guangtao , Liu Zhiwen , Tan Bin , Zhang Qingbo , Zhang Liping , Zhang Haibo , Zhu Yiguang , Zhang Changsheng
Published: October 2021

Linearized berninamycin analogues were generated by heterologous expression of the ber biosynthetic gene cluster from deep-sea derived Streptomyces sp. SCSIO 11878 in S. albus, but neither in S. lividans nor in S. coelicolor.
A binary all-nanoporous composite membrane constructed via vapor phase transformation for high-permeance gas separation
Authors: Bu Mengqi , Feng Yang , Li Qingxun , Wang Yiran , Feng Shou , Zhang Kai , Jiang Yujie , Fan Lili , Kang Zixi , Sun Daofeng
Published: October 2021

A COF with a large pore size was incorporated into a MOF matrix to construct an all-nanoporous composite membrane for high-permeance gas separation.
Chemical synthesis of Nd2Fe14B/Fe–Co nanocomposite with high magnetic energy product
Authors: Ngo Hieu Minh , Lee Gyutae , Haider Syed Kamran , Pal Umapada , Hawari Thomi , Kim Kyung Min , Kim Jongryoul , Kwon Hae-Woong , Kang Young Soo
Published: October 2021

Nd2Fe14B is one of the most popular permanent magnets (PMs) possessing the best energy product (BH)max among the common PM materials.
Development of highly gas-permeable polymers by metathesis copolymerization of 1-(p-trimethylsilyl)phenyl-1-propyne with tert-butyl and silyl group-containing diphenylacetylenes
Authors: Lin Yi , Dong Jianrong , Sakaguchi Toshikazu , Hashimoto Tamotsu
Published: October 2021

Metathesis copolymerization of 1-(p-trimethylsilyl)phenyl-1-propyne with diphenylacetylenes was achieved and the gas permeability of polymer membranes was improved by the incorporation of 20% phenylpropyne unit.
A multifunctional hollow TPU fiber filled with liquid metal exhibiting fast electrothermal deformation and recovery
Authors: Xiong Yan , Xiao Jieyu , Chen Juan , Xu Da , Zhao Shanshan , Chen Shangbi , Sheng Bin
Published: October 2021

We present a deformable conductive fiber composed of a hollow TPU fiber filled with liquid metal, which can realize fast shape transformation by electrothermal heating, for multifunctional applications.
Rationally designed yolk–shell Co9S8–Co1−xS hollow spheres for advanced sodium-ion storage
Authors: Luo Yuanyi , Shi Ludi , He Huanze , Cong Guangtao , Zhu Caizhen , Xu Jian
Published: October 2021

Rationally-designed nitrogen-doped carbon-coated Co9S8–Co1−xS yolk–shell hollow spheres are synthesized to buffer the volume fluctuation and enhance the electrical/ionic conductivity.