bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals
Authors: Li Yan , Leveau Aymeric , Zhao Qiang , Feng Qi , Lu Hengyun , Miao Jiashun , Xue Zheyong , Martin Azahara C. , Wegel Eva , Wang Jing , Orme Anastasia , Rey Maria-Dolores , Karafiátová Miroslava , Vrána Jan , Steuernagel Burkhard , Joynson Ryan , Owen Charlotte , Reed James , Louveau Thomas , Stephenson Michael J. , Zhang Lei , Huang Xuehui , Huang Tao , Fan Danling , Zhou Congcong , Tian Qilin , Li Wenjun , Lu Yiqi , Chen Jiaying , Zhao Yan , Lu Ying , Zhu Chuanrang , Liu Zhenhua , Polturak Guy , Casson Rebecca , Hill Lionel , Moore Graham , Melton Rachel , Hall Neil , Wulff Brande B. H. , Doležel Jaroslav , Langdon Tim , Han Bin , Osbourn Anne 
Published: May 2021

AbstractNon-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat—the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a ‘self-poisoning’ scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.
Development of a valid Chinese version of the Cumberland Ankle Instability Tool in Chinese-speaking patients with chronic ankle instability disorders
Authors: Wang Wei , Liao Dongfa , Kang Xia , Zheng Wei , Xu Wei , Chen Song , Xie Qingyun 
Published: May 2021

AbstractAs an effective scale for the condition assessment of patients with chronic ankle instability (CAI), the Cumberland Ankle Instability Tool (CAIT) is the most widely used scale, and its original version is written in English. Therefore, the purpose of our study is to apply the CAIT to Chinese patients and evaluate its responsiveness, reliability, and validity in terms of Chinese patients with CAI. First, we adapted the CAIT into the Chinese edition (CAIT-C), through which cross-cultural adaptation and translation can be carried out in a five-step procedure. Next, recruited patients completed the three periods of the Foot and Ankle Ability Measure (FAAM), CAIT-C, and the Medical Outcomes Study Short-Form 36 (SF-36) scales. Afterward, to assess the responsiveness, reliability, and validity, we calculated the standardized response mean (SRM), effect size (ES), Spearman's correlation coefficient (rs), minimal detectable change (MDC), standard error of measurement (SEM), intraclass correlation coefficient (ICC), and Cronbach’s alpha. Generally, in the use of CAI, 131, 119, and 86 patients favorably completed the three periods of the scales. The CAIT-C was proven to have good test–retest reliability (ICC = 0.930) and fine internal consistency (Cronbach’s alpha = 0.845–0.878). The low-value of MDC (0.04–2.28) and SEM (1.73) show it is possible to detect clinical changes when we take advantage of CAIT-C. Good or moderate correlations (rs = 0.422–0.738) were gained from the physical subscales of the SF-36 and the subscales of the FAAM and the CAIT-C. Fair or poor correlations (rs = 0.003–0.360) were gained between the mental subscales of the SF-36 and the CAIT-C, which sufficiently indicated that the CAIT-C had good validity. Moreover, good responsiveness was observed in the CAIT-C (ES = 1.316, SRM = 1.418). The CAIT-C scale is an effective, valid, and reliable tool to evaluate Chinese CAI patients.
Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise
Authors: Abend M. , Amundson S. A. , Badie C. , Brzoska K. , Hargitai R. , Kriehuber R. , Schüle S. , Kis E. , Ghandhi S. A. , Lumniczky K. , Morton S. R. , O’Brien G. , Oskamp D. , Ostheim P. , Siebenwirth C. , Shuryak I. , Szatmári T. , Unverricht-Yeboah M. , Ainsbury E. , Bassinet C. , Kulka U. , Oestreicher U. , Ristic Y. , Trompier F. , Wojcik A. , Waldner L. , Port M. 
Published: May 2021

AbstractLarge-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5–40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 °C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5–8 h varying exposure times; second: varying dose rates of 0.5–8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in ≥ 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 °C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 °C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 °C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.
Tracking the time course of reproduction number and lockdown’s effect on human behaviour during SARS-CoV-2 epidemic: nonparametric estimation
Authors: Pillonetto G. , Bisiacco M. , Palù G. , Cobelli C. 
Published: May 2021

AbstractUnderstanding the SARS-CoV-2 dynamics has been subject of intense research in the last months. In particular, accurate modeling of lockdown effects on human behaviour and epidemic evolution is a key issue in order e.g. to inform health-care decisions on emergency management. In this regard, the compartmental and spatial models so far proposed use parametric descriptions of the contact rate, often assuming a time-invariant effect of the lockdown. In this paper we show that these assumptions may lead to erroneous evaluations on the ongoing pandemic. Thus, we develop a new class of nonparametric compartmental models able to describe how the impact of the lockdown varies in time. Our estimation strategy does not require significant Bayes prior information and exploits regularization theory. Hospitalized data are mapped into an infinite-dimensional space, hence obtaining a function which takes into account also how social distancing measures and people’s growing awareness of infection’s risk evolves as time progresses. This also permits to reconstruct a continuous-time profile of SARS-CoV-2 reproduction number with a resolution never reached before in the literature. When applied to data collected in Lombardy, the most affected Italian region, our model illustrates how people behaviour changed during the restrictions and its importance to contain the epidemic. Results also indicate that, at the end of the lockdown, around$$12\%$$12%of people in Lombardy and$$5\%$$5%in Italy was affected by SARS-CoV-2, with the fatality rate being 1.14%. Then, we discuss how the situation evolved after the end of the lockdown showing that the reproduction number dangerously increased in the summer, due to holiday relax, reaching values larger than one on August 1, 2020. Finally, we also document how Italy faced the second wave of infection in the last part of 2020. Since several countries still observe a growing epidemic and others could be subject to other waves, the proposed reproduction number tracking methodology can be of great help to health care authorities to prevent SARS-CoV-2 diffusion or to assess the impact of lockdown restrictions on human behaviour to contain the spread.
Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn’s disease
Authors: Li Yuan , Wang Zhiming , Wu Xiuwen , Wang Gefei , Gu Guosheng , Ren Huajian , Hong Zhiwu , Ren Jianan 
Published: May 2021

AbstractThe purpose of this study was to evaluate genome-wide DNA methylation changes in intestinal mucosa tissue of adult patients with Crohn's disease comprehensively. DNA methylation chip was used to analyze abnormal methylation sites among penetrating and non-penetrating intestinal mucosa tissue of Crohn's disease and normal intestinal mucosa tissue of healthy controls. Methylation abnormalities of different locus were verified by pyrosequencing and quantitative polymerase chain reaction. Differential DNA methylation sites were participated in the positive regulation of apoptosis and the positive regulation of IL-8 production and were enriched in signaling pathways related to inflammatory bowel disease and extracellular matrix receptor interaction signaling pathways. Correlation analysis showed that the methylation abnormalities of HLA-DRB1 (r = − 0.62, P < 0.001), MUC1 (r = − 0.45, P = 0.01), YPEL5 (r = − 0.55, P = 0.001) and CBLB (r = − 0.62, P < 0.001) were significantly negatively correlated with their relative expression levels. The degree of methylation abnormality of MUC1 was negatively correlated with the disease activity score of Crohn's disease (r = − 0.50, P = 0.01). Apoptosis, interleukin-8 production and abnormal extracellular matrix might be involved in the mechanism of penetrating intestinal mucosal lesions in Crohn's disease. The degree of abnormal methylation of MUC1 was negatively correlated with the disease activity of Crohn's disease.
Immunocompatibility of a new dual modality contrast agent based on radiolabeled iron-oxide nanoparticles
Authors: Karageorgou Maria-Argyro , Stamopoulos Dimosthenis 
Published: May 2021

AbstractRadiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications. The immunocompatibility of a new DMCA is a prerequisite for subsequent in vivo applications. Here, a new DMCA, namely Fe3O4 nanoparticles radiolabeled with 68Ga, is subjected to immunocompatibility tests both in vitro and in vivo. The in vitro immunocompatibility of the DMCA relied on incubation with donated human WBCs and PLTs (five healthy individuals). Optical microscopy (OM) and atomic force microscopy (AFM) were employed for the investigation of the morphological characteristics of WBCs and PLTs. A standard hematology analyzer (HA) provided information on complete blood count. The in vivo immunocompatibility of the DMCA was assessed through its biodistribution among the basic organs of the mononuclear phagocyte system in normal and immunodeficient mice (nine in each group). In addition, Magnetic Resonance Imaging (MRI) data were acquired in normal mice (three). The combined OM, AFM and HA in vitro data showed that although the DMCA promoted noticeable activation of WBCs and PLTs, neither degradation nor clustering were observed. The in vivo data showed no difference of the DMCA biodistribution between the normal and immunodeficient mice, while the MRI data prove the efficacy of the particular DMCA when compared to the non-radiolabeled, parent CA. The combined in vitro and in vivo data prove that the particular DMCA is a promising candidate for future in vivo applications.
Understanding the structural, optical, and dielectric characteristics of SrLaLiTe1−xMnxO6 perovskites
Authors: Halizan M. Z. M. , Mohamed Z. , Yahya A. K. 
Published: May 2021

AbstractIn electronic applications, good dielectric permittivity material has huge potential in the capacitive energy storage devices. Herein, in the present work the dielectric study of SrLaLiTe1−xMnxO6(x = 0.02, 0.04, 0.06, 0.08, and 0.10) double perovskites has been studied and discussed. These compounds were prepared through solid-state reaction method. All of the prepared compounds were confirmed to crystallized in monoclinic structure ofP21/nspace symmetry with better crystallization when dopant concentrations increased untilx = 0.08. The formation of Li–O–Te/Mn bonds in octahedral structures in all compounds were confirmed in this study. The existence of peaks at specific wavenumbers indicated vibrations of B–site cations’ bonds. When dopant amounts were increased fromx = 0.02 tox = 0.08, there was an increasing trend of grains sizes formation in the compounds. The discussions on effects of grain sizes towards dielectric properties were included in this paper. Other important results and discussions comprised of the significant effects of dopant on the optical band gap (Eopt) and absorption frequencies of the compounds. The decreasing trend ofEopttowards semiconductor range indicated the compounds’ promising potentials for optoelectronic device application.
High loading of trimethylglycine promotes aqueous solubility of poorly water-soluble cisplatin
Authors: Kadokawa Riki , Fujie Tetsuo , Sharma Gyanendra , Ishibashi Kojiro , Ninomiya Kazuaki , Takahashi Kenji , Hirata Eishu , Kuroda Kosuke 
Published: May 2021

AbstractTrimethylglycine (TMG) is a cheap, natural, and highly biocompatible compound. Therefore, it has been used in the fields of food and life sciences, but the application of solid TMG is limited to utilisation as an “additive”. In the present study, we focussed on the high solubility of TMG in water, derived from the aprotic zwitterionic structure, and proposed TMG as the chemical accounting for a major portion of the aqueous solution (e.g., 50 wt%). High loading of TMG shifted the properties of water and enabled the dissolution of poorly water-soluble cisplatin, an anticancer agent, at high concentration (solubility of cisplatin: 0.15 wt% in watervs1.7 wt% in TMG aqueous solution). For hepatic arterial infusion, this can reduce the amount of cisplatin administered from 40 to 4 mL. It enables simple injection using a syringe, without the need for catheters and automatic pumps, leading to critical alleviation of the risk to patients. Furthermore, we produced a dry powder from a cisplatin-containing TMG aqueous solution via freeze-drying. Powders can be conveniently stored and transported. Furthermore, cisplatin is often used as a mixture with other drugs, and cisplatin aqueous solutions are not preferred as they dilute the other drugs.
Characteristics of soil salt crust formed by mixing calcium chloride with sodium sulfate and the possibility of inhibiting wind-sand flow
Authors: Li Shenghui , Li Chengzhi , Fu Xiaolei 
Published: May 2021

AbstractSoil salt crust can change the structure of aeolian soil and improve its resistance to wind erosion. Four ions (Na+, Ca2+, Cl−, and SO42−) with high contents in aeolian soil were selected for a salt crust experiment. The experiment set a variety of gradients of soil salt contents and salt mixing ratios of Na2SO4 and CaCl2. The physical properties of the salt crust were tested, and the wind erosion resistance of the salt crust was discussed. The results showed that the soil salt contents and salt mixing ratio influenced the resistance of the salt crust, especially in terms of its compressive strength and toughness. The former affected the compressive strength of the salt crust by changing the amount of cemented soil salt. The latter affected the kinds of crystals by changing the ion ratio, thus changing the structure of the salt crust and affecting its wind erosion resistance. The wind erosion resistance of the salt crust is complicated by the interaction between the soil salt content and salt mixing ratio. A multilayer crust can be formed in mixed salt, which has a strong wind erosion resistance. This result provides new findings on flowing sand soil and a new method for the treatment of flowing sand soil.
Spotlight on PSMA as a new theranostic biomarker for bladder cancer
Authors: Tumedei Maria Maddalena , Ravaioli Sara , Matteucci Federica , Celli Monica , De Giorgi Ugo , Gunelli Roberta , Puccetti Maurizio , Paganelli Giovanni , Bravaccini Sara 
Published: May 2021

AbstractBladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.
Cold-induction of afadin in brown fat supports its thermogenic capacity
Authors: Lundh Morten , Altıntaş Ali , Tozzi Marco , Fabre Odile , Ma Tao , Shamsi Farnaz , Gerhart-Hines Zachary , Barrès Romain , Tseng Yu-Hua , Emanuelli Brice 
Published: May 2021

AbstractThe profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.
Low human dystrophin levels prevent cardiac electrophysiological and structural remodelling in a Duchenne mouse model
Authors: Marchal Gerard A. , van Putten Maaike , Verkerk Arie O. , Casini Simona , Putker Kayleigh , van Amersfoorth Shirley C. M. , Aartsma-Rus Annemieke , Lodder Elisabeth M. , Remme Carol Ann 
Published: May 2021

AbstractDuchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder caused by loss of dystrophin. This lack also affects cardiac structure and function, and cardiovascular complications are a major cause of death in DMD. Newly developed therapies partially restore dystrophin expression. It is unclear whether this will be sufficient to prevent or ameliorate cardiac involvement in DMD. We here establish the cardiac electrophysiological and structural phenotype in young (2–3 months) and aged (6–13 months) dystrophin-deficient mdx mice expressing 100% human dystrophin (hDMD), 0% human dystrophin (hDMDdel52-null) or low levels (~ 5%) of human dystrophin (hDMDdel52-low). Compared to hDMD, young and aged hDMDdel52-null mice displayed conduction slowing and repolarisation abnormalities, while only aged hDMDdel52-null mice displayed increased myocardial fibrosis. Moreover, ventricular cardiomyocytes from young hDMDdel52-null animals displayed decreased sodium current and action potential (AP) upstroke velocity, and prolonged AP duration at 20% and 50% of repolarisation. Hence, cardiac electrical remodelling in hDMDdel52-null mice preceded development of structural alterations. In contrast to hDMDdel52-null, hDMDdel52-low mice showed similar electrophysiological and structural characteristics as hDMD, indicating prevention of the cardiac DMD phenotype by low levels of human dystrophin. Our findings are potentially relevant for the development of therapeutic strategies aimed at restoring dystrophin expression in DMD.
Half-life modeling of basic fibroblast growth factor released from growth factor-eluting polyelectrolyte multilayers
Authors: Ding Ivan , Peterson Amy M. 
Published: May 2021

AbstractGrowth factor-eluting polymer systems have been widely reported to improve cell and tissue outcomes; however, measurements of actual growth factor concentration in cell culture conditions are limited. The problem is compounded by a lack of knowledge of growth factor half-lives, which impedes efforts to determine real-time growth factor concentrations. In this work, the half-life of basic fibroblast growth factor (FGF2) was determined using enzyme linked immunosorbent assay (ELISA). FGF2 release from polyelectrolyte multilayers (PEMs) was measured and the data was fit to a simple degradation model, allowing for the determination of FGF2 concentrations between 2 and 4 days of culture time. After the first hour, the FGF2 concentration for PEMs assembled at pH = 4 ranged from 2.67 ng/mL to 5.76 ng/mL, while for PEMs assembled at pH = 5, the concentration ranged from 0.62 ng/mL to 2.12 ng/mL. CRL-2352 fibroblasts were cultured on PEMs assembled at pH = 4 and pH = 5. After 2 days, the FGF2-eluting PEM conditions showed improved cell count and spreading. After 4 days, only the pH = 4 assembly condition had higher cells counts, while the PEM assembled at pH = 5 and PEM with no FGF2 showed increased spreading. Overall, the half-life model and cell culture study provide optimal concentration ranges for fibroblast proliferation and a framework for understanding how temporal FGF2 concentration may affect other cell types.