bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural dynamics of AAA+ ATPase Drg1 and mechanism of benzo-diazaborine inhibition
Authors: Gao Ning , Ma Chengying , Wu Damu , Chen Qian 
Published: January 2022

Abstract
The AAA+ ATPase Drg1 is a ribosome assembly factor in yeast, and functions to release Rlp24, another assembly factor, from the pre-60S particle just exported from nucleus to initiate its further cytoplasmic maturation. Being a type II AAA+ protein with two ATPase domains (D1 and D2), its activity in ribosome assembly can be inhibited by a drug molecule diazaborine. In human, mutations of Drg1 homologue has been linked to a disease condition called epilepsy, hearing loss, and mental retardation syndrome. Although the general structure of Drg1 hexamer was recently reported, its complete structure and dynamic conformational rearrangements driven by ATP-hydrolysis are poorly understood. Here, we report a comprehensive structural characterization of Drg1 hexamers in different nucleotide-binding and benzo-diazaborine treated states. Our data show that Drg1 hexamers transits between two extreme conformations, characterized by a planar or helical arrangement of its six protomers. By forming covalent adducts with the ATP molecules in the active centers of both D1 and D2, benzo-diazaborine locks Drg1 hexamers in a more symmetric and non-productive conformation. In addition, we obtained the structure of a mutant Drg1 hexamer (Walker B mutations) with a polypeptide trapped in the central channel, representing a 3D snapshot of its functional, substrate-processing form. Conserved pore loops on the ATPase domains of Drg1 form a spiral staircase to interact with the substrate through a sequence-independent manner. These results suggest that Drg1, similar as Cdc48/p97, acts as a molecular unfoldase to remodel pre-60S particles, and benzo-diazaborine inhibits both the inter-protomer and inter-ring communication to disable the conformational cycling of Drg1 protomers required for the unfolding activity.
The Effects and Mechanisms of Action of TC-G 1008, GPR39 Agonist, in Animal Models of Seizures and Epilepsy
Authors: Doboszewska Urszula , Socala Katarzyna , Pieróg Mateusz , Nieoczym Dorota , Sawicki Jan , Szafarz Małgorzata , Gaweł Kinga , Rafalo-Ulińska Anna , Wyska Elżbieta , Esguerra Camila V. , Szewczyk Bernadeta , Maćkowiak Marzena , Młyniec Katarzyna , Nowak Gabriel , Sowa Ireneusz , Wlaź Piotr 
Published: January 2022

Abstract
Background and purpose: The G-protein coupled receptor 39 (GPR39) may be activated by zinc ions. Activation of GPR39 was suggested as a novel pharmacological strategy for treating seizures. Experimental approach: We utilized a specific agonist of GPR39, TC-G 1008, and the nonspecific agonist, zinc chloride and a variety of models of acute seizures or a chronic model of epilepsy which were induced in non-genetically modified mice, GPR39 knockout mice or in zebrafish larvae. We examined total serum zinc (by Inductively Coupled Plasma Optical Emission Spectrometry) as well as intracellular zinc ([Zn2+]I) (by Zinpyr-1 staining) concentrations and the expression of selected proteins (by Western blot) which are associated with GPR39 signaling in the hippocampus. Key results: Liquid chromatography tandem mass spectrometry analysis showed that TC-G 1008 is brain penetrant. TC-G 1008 decreased the seizure threshold in the maximal electroshock seizure (MES) threshold test, but it increased the seizure threshold in the 6-Hz induced seizure threshold test. The behavioral effects of TC-G 1008 and MES or 6-Hz seizure were accompanied by alterations in hippocampal [Zn2+]I. TC-G 1008 increased the mean duration of EEG discharges in response to pentylenetetrazole (PTZ) in zebrafish larvae and facilitated the development of PTZ kindling in mice. Using GPR39 knockout mouse line, generated by the CRISPR-Cas-9 method, we showed that GPR39 is a target for TC-G 1008 regarding PTZ-induced epileptogenesis. Conclusion and implications: Our in vivo data obtained using TC-G 1008 generally argue against GPR39 activation as a therapeutic strategy for alleviating seizures/epilepsy.
The Effects of Short-term Pm 2.5 Exposure on Pulmonary Function Among Children With Asthma——A Panel Study in Shanghai, China
Authors: Zhou Ji , Lei Ruoyi , Xu Jianming , Li Peng , Ye Xiaofang , Yang Dandan , Yang Sixu , Yin Yong , Zhang Renhe 
Published: January 2022

Abstract
BackgroundFine particulate matter with aerodynamic diameter ≤ 2.5 mm (PM2.5) has been reported to be an important risk factor for asthma. Our study was designed to evaluate the relationship between air PM2.5 and lung function among children with asthma in Shanghai, China. MethodsFrom 2016 to 2019, a total of 70 Chinese children aged 4 to 14 in Pudong, Shanghai were recruited for this panel study. Upon entry to the group, questionnaire was used to collect basic information, and the lung function covering forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were carried out for each child more than two times during follow-up. Meanwhile, the simultaneous daily air atmospheric pollutants and meteorological data were collected. The linear mixed effect (LME) model was used to assess the relationship between air pollutants and lung function adjusting other covariates like sex, age, season and so on. ResultsA significantly negative association was found between PM2.5 level and lung function in children with asthma. In the single-pollutant model, the largest effect of PM2.5 on lung function were found on lag 0-2, FVC and FEV1 decreased by 0.91% [95% confidence interval (CI): -1.75, -0.07] and 1.05% (95% CI: -2.09, 0.00) for every 10 mg/m3 increase of PM2.5. In the multi-pollution model (adjusted PM2.5+SO2+O3), the maximum effect of PM2.5 on FVC and FEV1 also appeared on lag 0-2, FVC and FEV1 decreased by 1.57% (95% CI: -2.69, -0.44) and 1.67% (95% CI: -3.05, -0.26) for every 10 mg/m3 increase of PM2.5, respectively. In the subgroup analysis, boys, children and hot season more were sensitive. ConclusionThe short-term exposure of ambient PM2.5 is a risk factor for the lung function of children with asthma, particularly in boys, preschoolers (<6 years old) and in the hot season.
Mutations at Codon 641 of Exon 16 of EZH2 in Circulating Tumor DNA: A Biomarker for Relapse in Patients With Diffuse Large B-cell Lymphoma Treated With the R-CHOP Scheme.
Authors: Díaz-Chávez José , Gutiérrez-Hernández Olga , Taja-Chayeb Lucia , Gutiérrez-Chavarría Sindy , Aviles-Salas Alejandro , Candelaria Myrna 
Published: January 2022

Abstract
Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), methylates H3K27, resulting in transcriptional silencing. The mutation at Y646 amino acid in the EZH2 gene is mutated in up to 40 % of B-cell lymphomas. Methods: We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. The mutations were determined by sanger sequencing, and by ddPCR. We also evaluated the impact of these mutations on response, relapse, and survival. Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25-75) was 23 (7- 42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52 % and 99 %, respectively. After adding the ddPCR analysis, the Se and Sp increased to 95 and 100 %, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p=0.04), or EZH2 mutations were associated with relapse. The median PFS (95 % Interval confidence) was 27.7 (95 % IC: 14-40) vs 44.1 (95 % IC: 40-47.6) months for the mutated vs wt patients. Conclusions: The ctDNA is usefull to analyse EZH2 mutations, which have an impact in PFS.
One Bat’s Waste is Another Man’s Treasure: A DNA Metabarcoding Approach for the Assessment of Biodiversity and Ecosystem Services Using Bat Faeces
Authors: Curran Thomas , Browett Samuel , O'Neill David , O'Hanlon Aidan , O'Reilly Catherine , Harrington Andrew , McDevitt Allan , O'Meara Denise 
Published: January 2022

Abstract
Arthropod populations are constantly changing due to changes in climate and the globalisation of trade and travel. Effective and diverse monitoring techniques are required to understand these changes. DNA metabarcoding has facilitated the development of a broad monitoring method to sample arthropod diversity from environmental and faecal samples. In this study, we applied DNA metabarcoding to DNA extracted from bat faecal pellets of Rhinolophus hipposideros, the lesser horseshoe bat in Ireland, a highly protected bat species of conservation concern in Europe. From as few as 24 bat faecal pellets, we detected 161 arthropod species, spanning 11 orders, including 38 pest species of which five were determined to be priority pests, highlighting important ecosystem services. We also report the identification 14 species not previously reported in Ireland, but upon further investigation found that many of these are likely misidentified due to inadequacies in the genetic reference database. For the first time, we were able to use non-invasively collected bat samples to examine the role of sex in the diet of bats and found that the male and female diets did not differ significantly. However, sampling location did explain variation within the diet, highlighting how landscape features influence arthropod composition and diversity. We discuss the current limitations of the methodology in Ireland, how these can be overcome in future studies, and how this data can be used for biodiversity monitoring and informing conservation management of protected bat species.
Development of “NEC-SD-LAMP,” a New Non-Electrified Infectious Diseases Testing Method
Authors: Kimura Yusuke , Ikeuchi Masashi 
Published: January 2022

Abstract
Here, non-electric-control SalivaDirect loop-mediated isothermal amplification (NEC-SD-LAMP), which can detect infections by analyzing viral gene expression in saliva without electrical control systems, was developed. In this method, viral genes are purified from saliva using SalivaDirect, and gene expression is analyzed by loop-mediated isothermal amplification (LAMP) by adding water to the device, and the results can be visually confirmed. Melting palmitic acid maintains the optimal temperature for the LAMP reaction, as the temperature of palmitic acid is maintained at 62.9°C, its melting point. By taking advantage of the proximity of this melting point to the optimal temperature for LAMP, it is possible to perform LAMP without electricity. Using this method, adenovirus DNA was detected in saliva. Furthermore, the detection limit was 2 copies per µL, indicating that it is possible to detect viral infections in saliva even before the onset of SARS-CoV-2 infection.
The Effect of Low Intensity Pulsed Ultrasound on Endometrial Receptivity in Infertile Patients with Adenomyosis
Authors: Long Ling , Zhou Ling , Zhu Jing , He Xuan 
Published: January 2022

Abstract
Objective: Adenomyosis (AM) is an important cause of female infertility, and its disease mechanism remains unclear. This study preliminarily investigated the expression of endometrial receptivity markers homeobox A10 (HOXA10) and leukemia inhibitory factor (LIF) in infertile patients with AM and described the effects of low intensity pulsed ultrasound (LIPUS) on it. Methods: In vivo, tissues were obtained from the infertile female AM patient group (AG group, n=10) and healthy control group (CG group, n=11). The expression of HOXA10 and LIF in the two groups was detected by immunohistochemistry (IHC) and western blotting. In vitro, primary cells were extracted and cultured from the two groups, and the expression of HOXA10 and LIF protein was detected by western blotting. Then the AG cells were treated with 15, 30, and 60 mW/cm2 of LIPUS for 7 days (20 min/day), and detected the cell adhesion rate. Finally, treat the AG cells with 30mW/cm2 LIPUS for 7 days (20 min/day), and detect the expression level of ICAM-1 in the cell supernatant by ELISA. The AG cells was treated with 30 mW/cm2 LIPUS for 4 days (20 min/day), and the expression levels of HOXA10 and LIF were detected by western blotting, RT-PCR, and agarose gel electrophoresis. Results: In vivo, IHC staining showed that HOXA10 and LIF proteins were mainly localized in endometrial epithelial cells. Both IHC and western blot showed that the levels of HOXA10 and LIF in the AG group were significantly lower than those in the CG group (P<0.01, P<0.05). In vitro, the expression levels of HOXA10 and LIF protein in the AG cell was significantly lower than those in the CG cell (P<0.001). Then, the cell adhesion ability of the 30 and 60 mW/cm2 groups was higher than that of the 15 mW/cm2 group after LIPUS treatment. Finally, The concentration of ICAM-1 in the supernatant of AG cells treated with LIPUS was significantly higher than that of the control group (P<0.01), and the AG cells were treated with 30 mW/cm2 LIPUS for 4 days (20 min/day), the protein and mRNA expression levels of HOXA10 and LIF were higher than those of the control group (P<0.001). Conclusion: The reduction of HOXA10 and LIF may be one of the reasons for the decreased endometrial receptivity in AM. The LIPUS promoted the adhesion and the expression of HOXA10 and LIF of EEECs from the AM group, thereby increasing endometrial receptivity.
DD-KARB: Data-Driven Compliance to Quality by Rule Based Benchmarking
Authors: Besharati Mohammad Reza , Izadi Mohammad 
Published: January 2022

Abstract
Rather than proof and logical evaluation, benchmarking can be used for compliance assessment. Naturally, a set of benchmarks can shape an applied solution to compliance assessment. This paper proposes the KARB solution system, i.e. preventing compliance anomalies through rule-based benchmarking. In fact, rule-based benchmarking means evaluating an under-compliance system with its symbolic specification and using a set of symbolic rules (on the behalf of the semantic logic of evaluation). A case study was conducted to demonstrate and analyze the KARB solution. The IR-QUMA study (Iranian Survey on Quality in Messenger Apps) was then conducted to evaluate the quality of some messenger applications. According to the evaluation results, the hybrid DD-KARB method (with a combination of semantics-awareness and data-drivenness) is more effective than solo methods and can compute a somehow good estimation for the messenger application user quality scores. Therefore, DD-KARB can be considered a method for quality benchmarking in this technical context.
Rethinking of The Zone of Proximal Development: The Role of Parental Engagement in Children's Language Learning Skills
Authors: Akbari Elham 
Published: January 2022

Abstract
The present research investigated the efficacy of parent engagement in children's learning and achievement in the English language. It is emphasized that adult guidance in foreign language learning cannot necessarily play an influential role in children's zone of proximal development (ZPD). It seems that parents or adults should enjoy relative linguistic skills, while in Vygotsky's theory, there is ambiguity over some concepts such as adult guidance characteristics.The statistical society consisted of sixty Iranian children ranging from 9 to 10, divided randomly into three groups of experimental 1, experimental 2, and control. Children received face-to-face education while Telegram was used for their parents. The research results showed significantly more learning, skill training, parent involvement, and shared activities between children and parents in the experimental1 and experimental 2 groups compared to the control group. Moreover, a positive correlation is found between parent involvement and children's achievement in all three groups. The results also showed that parents' involvement and teaching involvement, and language skills had the most influence on parents' involvement. Furthermore, teaching engagement to parents had the most significant influence on children's activities. In addition, children's activities and language skill training had the most influence on their learning.
b-value of what? Complex behavior of the magnitude distribution during and within the 2016–2017 central Italy sequence
Authors: Herrmann Marcus , Piegari Ester , Marzocchi Warner 
Published: January 2022

Abstract
The Magnitude–Frequency-Distribution (MFD) of earthquakes is typically modeled with the (tapered) Gutenberg–Richter relation. The main parameter of this relation, the b-value, controls the relative rate of small and large earthquakes. Resolving spatiotemporal variations of the b-value is critical to understanding the earthquake occurrence process and improving earthquake forecasting. However, this variation is not well understood. Here we present unexpected MFD variability using a high-resolution earthquake catalog of the 2016–2017 central Italy sequence. Isolation of seismicity clusters reveals that the MFD differs in nearby clusters, varies or remains constant in time depending on the cluster, and features an unexpected b-value increase in the cluster where the largest event will occur. These findings suggest a strong influence of the heterogeneity and complexity of tectonic structures on the MFD. Our findings raise the question of the appropriate spatiotemporal scale for resolving the b-value, which poses a serious obstacle to interpreting and using the MFD in earthquake forecasting.
Somatic Embryogenesis In Rosa Chinensis CV. ‘Parson’s Pink China’
Authors: Cai Yanfang , Tang Lintao , Chen Haixia , Li Yufan , Liu Rong , Chen Jiren 
Published: January 2022

Abstract
This study investigated the effects of explant type, plant growth regulator concentration, callis status, medium conversion time, and medium tilt on the growth of rose somatic embryos. The results showed that Rosa chinensis cv. ‘Parson’s Pink China’ leaves could induce normal embryogenic calli but petioles could not. When the 2,4-dichlorophenoxyacetic acid concentration was 3.0 mg/L, the callis induction rate was the highest in the embryo proliferation medium (EP medium) supplemented with 0.5mg/L kinetin, and white and reddish-brown translucent calli were the main type of embryogenic calli induced. As the culture time in EP medium was extended, the relative induction rate for secondary embryos and multicotyledon secondary embryos gradually increased when transferred to embryo maturation medium (EM medium), but the induction rate for somatic embryos decreased. Placing the EM medium at an angle of 45° made the somatic embryos germinate faster and the germination rate was also higher. The germination buds produced by the somatic embryos with two cotyledons showed the fastest germination and greatest survival rates. The results of this experiment will help improve somatic embryo regeneration rates and explore new ways of regeneration, and lays the foundation for further optimization of the somatic embryo genetic transformation system.
Spatial and molecular profiling of the classic Hodgkin lymphoma microenvironment reveals an immunosuppressive mononuclear phagocyte network
Authors: Stewart Benjamin , Fergie Martin , Young Matthew , Jones Claire , Sachdeva Ashwin , Blain Alex , Bacon Chris , Rand Vikki , Ferdinand John , James Kylie , Mahbubani Krishnaa , Hook Liz , Jonas Nicolaas , Coleman Nicholas , Saeb-Parsy Kourosh , Collin Matthew , Clatworthy Menna , Behjati Sam , Carey Christopher 
Published: January 2022

Abstract
Although a lymph node infiltrated by classic Hodgkin lymphoma is mostly composed of non-neoplastic immune cells, the malignant Hodgkin Reed-Sternberg cells (HRSC) successfully suppress an anti-tumor immune response, to create a cancer-permissive microenvironment. Accordingly, unleashing the dormant immune cells, for example by checkpoint inhibition, has been a central focus of recent therapeutic advances for this disease. Here, we profiled the global immune cell composition of normal and diseased lymph nodes by single-cell RNA sequencing, as a basis for interrogating the immediate vicinity of HRSC, first regionally and then at cellular resolution. Our analyses revealed specific immune cells and functional states associated with HRSC. Most prominently, we discovered a non-random spatial association of immunoregulatory mononuclear phagocytes positioned around HRSC, which express the immune checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO1. These findings provide a basis for rational targeting and activation of the anti-tumor immune response in classic Hodgkin lymphoma.
Restructuring of emergent grain boundaries at free surfaces – an interplay between core stabilization and elastic stress generation
Authors: Zhang Xiaopu , Wang Mengyuan , Wang Hailong , Upmanyu Moneesh , Boland John 
Published: January 2022

Abstract

Scanning tunneling microscopy and numerical calculations are used to study the structure and relaxation of grain boundaries at the surface of planar nanocrystalline copper (111) films and bicrystals. We show that the strong energetic preference for boundary cores to lie along close-packed planes introduces a restructuring that rotates adjoining grains and generates elastic stresses in the triple junction region. The interplay of this stress field and the core stabilization determines the length scale of the restructuring and controls the shape and magnitude of the displacement field around the triple junction. Depending on the in-plane angle, restructured boundaries can extend to depths of ~ 15 nm with the associated elastic stress fields extending to even greater depths. These results point to a new mechanism of boundary relaxation at surfaces that is expected to play an important role in grain coalescence and stress evolution in growing films.
On Channel Estimation and Power Control for Multi-cell Multi-path Massive MIMO TDD System
Authors: AMADID Jamal , Belhabib Abdelfettah , Boulouird Mohamed , Hassan Moha M’Rabet , Zeroual Abdelouhab 
Published: January 2022

Abstract
Some more practical channels that model the networks in a real environment is the multi-path communication channels. In order to investigate these communications channels. This work addressed Channel Estimation (CE) in the Uplink (UL) phase for a multi-cell multi-user massive multipleinput multiple-output (M-MIMO) system that studies multi-path communication between each user and its serving Base Station (BS). We suppose that the network operates under Time-Division Duplex (TDD) protocol. We studied and analyzed the multi-path channels and their benefit over CE since it presents a more realistic channel that displays a real propagation circumstance. on the flip side, we evaluated the CE quality using ideal MinimumMean Square Error (MMSE). This latter relies on an impractical property that can be explicated since the MMSE estimator considers foreknowledge on Large-Scale Fading (LSF) coefficients of interfering users. Thus, the suggested estimator is introduced to overcome this issue, where the suggested estimator tackled this problem and presented result asymptotic approaches to the performance of the MMSE estimator. Besides, we considered a more real communication in which the multi-path channels are either realized using Non-Line-of-Sight (NLoS) only or using both Line-of-Sight (LoS) and NLoS path depending on the distance at which the user is located from his serving BS. Otherwise, in numerous scenarios, users at the cell edge are strongly affected by Pilot Contamination (PC). Hence, we introduced a Power Control (PoC) policy so that the users at the cell edge are less affected by the PC problem. In the simulation results segment, the analytic and simulated results are introduced to assert our theoretical study.