bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of choroidal blood flow with autonomic dysfunction in patients with normal tension glaucoma
Authors: Shin Da Young , Hong Kyung Euy , Lee Na Young , Park Chan Kee , Park Hae Young L. 
Published: March 2022

AbstractThere is increasing evidence that autonomic dysfunction is an important factor in the progression of glaucoma. Mechanism of the association between autonomic dysfunction and progression of glaucoma is poorly understood. Since blood circulation is basically regulated by the autonomic nervous system, autonomic dysfunction may contribute to unstable or fluctuating blood pressure. Therefore, It is hypothesized that autonomic dysfunction may contribute to impaired ocular blood flow and lead to glaucoma progression. However, no clinical study yet has evaluated the relationship between ocular blood flow and autonomic nervous function. We enrolled 152 open angle glaucoma patient. Ocular blood flow was assessed by measuring vessel density (VD) using optical coherence tomography angiography, and autonomic nervous function was evaluated with heart-rate variability (HRV) parameters. The low frequency/high frequency (LF/HF) ratio, which is one of the HRV parameters, quantified the degree of sympathovagal balance. This indicator could represent autonomic dysfunction. Higher LF/HF ratio was associated with reduction of the deep parapapillary VD (R =  − 0.243, P = 0.003). Linear regression analysis showed a significant negative association between parapapillary choroidal VD and LF/HF ratio (β =  − 0.249; 95% confidential interval =  − 1.193 to − 0.249; P = 0.002) in multivariate analysis. We demonstarted the association between impaired ocular blood flow (parapapillary choroidal vessel density) and autonomic dysfunction (LF/HF ratio). This study could help understand the role of the autonomic dysfunction in pathophysiology of glaucoma progression.
MicroRNA-mediated post-transcriptional regulation of Pinus pinaster response and resistance to pinewood nematode
Authors: Modesto Inês , Inácio Vera , Van de Peer Yves , Miguel Célia M. 
Published: March 2022

AbstractPine wilt disease (PWD), caused by the parasitic nematode Bursaphelenchus xylophilus, or pinewood nematode (PWN), is a serious threat to pine forests in Europe. Pinus pinaster is highly susceptible to the disease and it is currently the most affected European pine species. In this work, we investigated the role of small RNAs (sRNAs) in regulating P. pinaster–PWN interaction in an early stage of infection. After performing an artificial PWN inoculation assay, we have identified 105 plant microRNAs (miRNAs) responsive to PWN. Based on their predicted targets, part of these miRNAs was associated with roles in jasmonate-response pathway, ROS detoxification, and terpenoid biosynthesis. Furthermore, by comparing resistant and susceptible plants, eight miRNAs with putative functions in plant defence and resistance to PWN have been identified. Finally, we explored the possibility of bidirectional trans-kingdom RNA silencing, identifying several P. pinaster genes putatively targeted by PWN miRNAs, which was supported by degradome analysis. Targets for P. pinaster miRNAs were also predicted in PWN, suggesting a role for trans-kingdom miRNA transfer and gene silencing both in PWN parasitism as in P. pinaster resistance to PWD. Our results provide new insights into previously unexplored roles of sRNA post-transcriptional regulation in P. pinaster response and resistance to PWN.
The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ
Authors: Toth Robert , Halmai Miklos , Gyorfy Zsuzsanna , Balint Eva , Unk Ildiko 
Published: March 2022

AbstractPCNA is a central orchestrator of cellular processes linked to DNA metabolism. It is a binding platform for a plethora of proteins and coordinates and regulates the activity of several pathways. The outer side of PCNA comprises most of the known interacting and regulatory surfaces, whereas the residues at the inner side constitute the sliding surface facing the DNA double helix. Here, by investigating the L154A mutation found at the inner side, we show that the inner surface mediates protein interactions essential for genome stability. It forms part of the binding site of Rad18, a key regulator of DNA damage tolerance, and is required for PCNA sumoylation which prevents unscheduled recombination during replication. In addition, the L154 residue is necessary for stable complex formation between PCNA and the replicative DNA polymerase δ. Hence, its absence increases the mutation burden of yeast cells due to faulty replication. In summary, the essential role of the L154 of PCNA in guarding and maintaining stable replication and promoting DNA damage tolerance reveals a new connection between these processes and assigns a new coordinating function to the central channel of PCNA.
Study on parameter optimization of deep hole cumulative blasting in low permeability coal seams
Authors: Zhao Dan , Shen Zhiyuan , Li Minghao , Liu Baichen , Chen Yinuo , Xie Lina 
Published: March 2022

AbstractCoal seam gas extraction is an important means of exploiting and utilizing gas resources, as well as a means of preventing coal mine disasters. To improve gas extraction efficiency in high gas and low permeability coal seams while ensuring blasting security, deep hole cumulative blasting parameters were optimized. ANSYS/LS-DYNA software is used to establish a 3-dimensional cumulative blasting model. By comparing and analyzing the blasting stress nephograms, stress time-history curves, and crack expansion curves, the optimal blasthole diameter, charge position, and charge length are obtained. Based on the numerical simulation results, a field test was carried out in the No. 10 coal seam of the Pingdingshan coal mine. The test results show that after cumulative blasting, the gas concentration was increased by an average of 2.25 times, the gas purity was increased by an average of 3.78 times, the permeability coefficient of the coal seam was increased by 21 times, and the effective radius of blasting was up to 7 m. The positive effects of deep hole cumulative blasting parameter optimization on the pressure relief and permeability enhancement of a high gas and low permeability coal seam were determined, which can provide a reference for other similar working faces to implement this technology.
Exploration of a modified stage for pN0 colon cancer patients
Authors: Liu Yunxiao , Zhang Hao , Wang Yuliuming , Zheng Mingyu , Wang Chunlin , Hu Hanqing , Tang Qingchao , Wang Guiyu 
Published: March 2022

AbstractExploring a modified stage (mStage) for pN0 colon cancer patients. 39,637 pN0 colon cancer patients were collected from the SEER database (2010–2015) (development cohort) and 455 pN0 colon cancer patients from the Second Affiliated Hospital of Harbin Medical University (2011–2015) (validation cohort). The optimal lymph nodes examined (LNE) stratification for cancer-specific survival (CSS) was obtained by X-tile software in the development cohort. LNE is combined with conventional T stage to form the mStage. The novel N stage was built based on the LNE (N0a: LNE ≥ 26, N0b: LNE = 11–25 and N0c: LNE ≤ 10). The mStage include mStageA (T1N0a, T1N0b, T1N0c and T2N0a), mStageB (T2N0b, T2N0c and T3N0a), mStageC (T3N0b), mStageD (T3N0c, T4aN0a and T4bN0a), mStageE (T4aN0b and T4bN0b) and mStageF (T4aN0c and T4bN0c). Cox regression model showed that mStage was an independent prognostic factor. AUC showed that the predictive accuracy of mStage was better than the conventional T stage for 5-year CSS in the development (0.700 vs. 0.678, P < 0.001) and validation cohort (0.649 vs. 0.603, P = 0.018). The C-index also showed that mStage had a superior model-fitting. Besides, calibration curves for 3-year and 5-year CSS revealed good consistencies between observed and predicted survival rates. For pN0 colon cancer patients, mStage might be superior to conventional T stage in predicting the prognosis.
In vitro characterisation of the MS2 RNA polymerase complex reveals host factors that modulate emesviral replicase activity
Authors: Wagner Alexander , Weise Laura I. , Mutschler Hannes 
Published: March 2022

AbstractThe RNA phage MS2 is one of the most important model organisms in molecular biology and virology. Despite its comprehensive characterisation, the composition of the RNA replication machinery remained obscure. Here, we characterised host proteins required to reconstitute the functional replicase in vitro. By combining a purified replicase sub-complex with elements of an in vitro translation system, we confirmed that the three host factors, EF-Ts, EF-Tu, and ribosomal protein S1, are part of the active replicase holocomplex. Furthermore, we found that the translation initiation factors IF1 and IF3 modulate replicase activity. While IF3 directly competes with the replicase for template binding, IF1 appears to act as an RNA chaperone that facilitates polymerase readthrough. Finally, we demonstrate in vitro formation of RNAs containing minimal motifs required for amplification. Our work sheds light on the MS2 replication machinery and provides a new promising platform for cell-free evolution.
Brain connectivity fingerprinting and behavioural prediction rest on distinct functional systems of the human connectome
Authors: Mantwill Maron , Gell Martin , Krohn Stephan , Finke Carsten 
Published: March 2022

AbstractThe prediction of inter-individual behavioural differences from neuroimaging data is a rapidly evolving field of research focusing on individualised methods to describe human brain organisation on the single-subject level. One method that harnesses such individual signatures is functional connectome fingerprinting, which can reliably identify individuals from large study populations. However, the precise relationship between functional signatures underlying fingerprinting and behavioural prediction remains unclear. Expanding on previous reports, here we systematically investigate the link between discrimination and prediction on different levels of brain network organisation (individual connections, network interactions, topographical organisation, and connection variability). Our analysis revealed a substantial divergence between discriminatory and predictive connectivity signatures on all levels of network organisation. Across different brain parcellations, thresholds, and prediction algorithms, we find discriminatory connections in higher-order multimodal association cortices, while neural correlates of behaviour display more variable distributions. Furthermore, we find the standard deviation of connections between participants to be significantly higher in fingerprinting than in prediction, making inter-individual connection variability a possible separating marker. These results demonstrate that participant identification and behavioural prediction involve highly distinct functional systems of the human connectome. The present study thus calls into question the direct functional relevance of connectome fingerprints.
PowerBacGWAS: a computational pipeline to perform power calculations for bacterial genome-wide association studies
Authors: Coll Francesc , Gouliouris Theodore , Bruchmann Sebastian , Phelan Jody , Raven Kathy E. , Clark Taane G. , Parkhill Julian , Peacock Sharon J. 
Published: March 2022

AbstractGenome-wide association studies (GWAS) are increasingly being applied to investigate the genetic basis of bacterial traits. However, approaches to perform power calculations for bacterial GWAS are limited. Here we implemented two alternative approaches to conduct power calculations using existing collections of bacterial genomes. First, a sub-sampling approach was undertaken to reduce the allele frequency and effect size of a known and detectable genotype-phenotype relationship by modifying phenotype labels. Second, a phenotype-simulation approach was conducted to simulate phenotypes from existing genetic variants. We implemented both approaches into a computational pipeline (PowerBacGWAS) that supports power calculations for burden testing, pan-genome and variant GWAS; and applied it to collections of Enterococcus faecium, Klebsiella pneumoniae and Mycobacterium tuberculosis. We used this pipeline to determine sample sizes required to detect causal variants of different minor allele frequencies (MAF), effect sizes and phenotype heritability, and studied the effect of homoplasy and population diversity on the power to detect causal variants. ﻿Our pipeline and user documentation are made available and can be applied to other bacterial populations. PowerBacGWAS can be used to determine sample sizes required to find statistically significant associations, or the associations detectable with a given sample size. We recommend to perform power calculations using existing genomes of the bacterial species and population of study.
Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires FcγRIIB and virus-antibody complex with bivalent interaction
Authors: Wang Shuang , Wang Junchao , Yu Xiaojuan , Jiang Wen , Chen Shuo , Wang Rongjuan , Wang Mingzhu , Jiao Shasha , Yang Yingying , Wang Wenbo , Chen Huilin , Chen Ben , Gu Chunying , Liu Chuang , Wang An , Wang Min , Li Gang , Guo Cuicui , Liu Datao , Zhang Jinchao , Zhang Min , Wang Lan , Gui Xun 
Published: March 2022

AbstractUnderstanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal structure determination and S trimer-binding modeling showed that MW01 and MW05 could bind to RBDs in S trimer with both “up” and “down” states. While, the neutralizing mAb MW07, which has no ADE activity only binds to RBD in S trimer with “up” state. Monovalent MW01 and MW05 completely diminished the ADE activity compared with their bivalent counterparts. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral infection. Blocking endosome transportation and lysosome acidification could inhibit the ADE activity mediated by MW05. Together, our results identified a novel ADE mechanism of SARS-CoV-2 pseudovirus in vitro, FcγRIIB-mediated uptake of SARS-CoV-2/mAb complex with bivalent interaction.
Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation
Authors: Ahn Jinsook , Jeong Soyeon , Kang So-mi , Jo Inseong , Park Bum-Joon , Ha Nam-Chul 
Published: March 2022

AbstractLamins are intermediate filaments that form a 3-D meshwork in the periphery of the nuclear envelope. The recent crystal structure of a long fragment of human lamin A/C visualized the tetrameric assembly unit of the central rod domain as a polymerization intermediate. A genetic mutation of S143F caused a phenotype characterized by both progeria and muscular dystrophy. In this study, we determined the crystal structure of the lamin A/C fragment harboring the S143F mutation. The obtained structure revealed the X-shaped interaction between the tetrameric units in the crystals, potentiated by the hydrophobic interactions of the mutated Phe143 residues. Subsequent studies indicated that the X-shaped interaction between the filaments plays a crucial role in disrupting the normal lamin meshwork. Our findings suggest the assembly mechanism of the 3-D meshwork and further provide a molecular framework for understanding the aging process by nuclear deformation.
Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family
Authors: Stogios Peter J. , Bordeleau Emily , Xu Zhiyu , Skarina Tatiana , Evdokimova Elena , Chou Sommer , Diorio-Toth Luke , D’Souza Alaric W. , Patel Sanket , Dantas Gautam , Wright Gerard D. , Savchenko Alexei 
Published: March 2022

AbstractThe environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment.
Secretory quality control constrains functional selection-associated protein structure innovation
Authors: Cheng Bin , Lv Jian-Min , Liang Yu-Lin , Zhu Li , Huang Xiao-Ping , Li Hai-Yun , Potempa Lawrence A. , Ji Shang-Rong , Wu Yi 
Published: March 2022

AbstractBiophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.
Multiscale reconstruction of various vessels in the intact murine liver lobe
Authors: Zhang Qi , Li Anan , Chen Siqi , Yuan Jing , Jiang Tao , Li Xiangning , Luo Qingming , Feng Zhao , Gong Hui 
Published: March 2022

AbstractThe liver contains a variety of vessels and participates in miscellaneous physiological functions. While past studies generally focused on certain hepatic vessels, we simultaneously obtained all the vessels and cytoarchitectural information of the intact mouse liver lobe at single-cell resolution. Here, taking structural discrepancies of various vessels into account, we reconstruct and visualize the portal vein, hepatic vein, hepatic artery, intrahepatic bile duct, intrahepatic lymph of an intact liver lobe and peribiliary plexus in its selected local areas, providing a technology roadmap for studying the fine hepatic vascular structures and their spatial relationship, which will help research into liver diseases and evaluation of medical efficacies in the future.
The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression
Authors: Guo Xin , Zhang Bo-fang , Zhang Jing , Liu Gen , Hu Qi , Chen Jing 
Published: March 2022

AbstractOur prior studies have characterized the participation of histone demethylase KDM3A in diabetic vascular remodeling, while its roles in myocardial ischemia/reperfusion (I/R) injury (MIRI) remain to be illustrated. Here we show that KDM3A was significantly downregulated in rat I/R and cellular hypoxia/reoxygenation (H/R) models. Subsequently, gain- and loss-of-function experiments were performed to investigate the effects of KDM3A in the settings of MIRI. KDM3A knockout exacerbated cardiac dysfunction and cardiomyocytes injury both in vivo and in vitro. The deteriorated mitochondrial apoptosis, reactive oxygen species, and inflammation were simultaneously observed. Conversely, KDM3A overexpression developed the ameliorated alternations in MIRI. Mechanistically, the MIRI-alleviating effects of KDM3A were associated with the enhancement of ETS1 expression. ChIP-PCR affirmed that KDM3A bound to the ETS1 promoter and removed dimethylation of histone H3 lysine 9 (H3K9me2), thus promoting ETS1 transcription. Our findings suggest that KDM3A is available for alleviating multi-etiologies of MIRI through the regulation of ETS1.
Southeast Asia must narrow down the yield gap to continue to be a major rice bowl
Authors: Yuan Shen , Stuart Alexander M. , Laborte Alice G. , Rattalino Edreira Juan I. , Dobermann Achim , Kien Le Vu Ngoc , Thúy Lưu Thị , Paothong Kritkamol , Traesang Prachya , Tint Khin Myo , San Su Su , Villafuerte Marcelino Q. , Quicho Emma D. , Pame Anny Ruth P. , Then Rathmuny , Flor Rica Joy , Thon Neak , Agus Fahmuddin , Agustiani Nurwulan , Deng Nanyan , Li Tao , Grassini Patricio 
Published: March 2022

AbstractSoutheast Asia is a major rice-producing region with a high level of internal consumption and accounting for 40% of global rice exports. Limited land resources, climate change and yield stagnation during recent years have once again raised concerns about the capacity of the region to remain as a large net exporter. Here we use a modelling approach to map rice yield gaps and assess production potential and net exports by 2040. We find that the average yield gap represents 48% of the yield potential estimate for the region, but there are substantial differences among countries. Exploitable yield gaps are relatively large in Cambodia, Myanmar, Philippines and Thailand but comparably smaller in Indonesia and Vietnam. Continuation of current yield trends will not allow Indonesia and Philippines to meet their domestic rice demand. In contrast, closing the exploitable yield gap by half would drastically reduce the need for rice imports with an aggregated annual rice surplus of 54 million tons available for export. Our study provides insights for increasing regional production on existing cropland by narrowing existing yield gaps.
Demand side management for solving environment constrained economic dispatch of a microgrid system using hybrid MGWOSCACSA algorithm
Authors: Basak Sourav , Dey Bishwajit , Bhattacharyya Biplab 
Published: March 2022

AbstractMicrogrids are a type of restricted power distribution systems in which electricity is generated, transmitted, and distributed within a small geographic region. They are used to ensure that renewable energy sources are used to their full potential. Microgrids provide further benefits, such as lowering transmission losses and the expenses associated with them. This research compares and contrasts the aims of economic dispatch, emission dispatch, fractional programing based combined economic emission dispatch, and environmental restricted economic dispatch (ECED). A low‐voltage microgrid system is investigated for three different scenarios. As a study optimization tool, an innovative, resilient, and strong hybrid swarm‐intelligence optimization algorithm is utilised, which is based on combining the properties of the traditional grey‐wolf optimiser, sine‐cosine algorithm, and crow search algorithm. The employment of a time‐of‐use energy market pricing approach instead of a fixed pricing plan resulted in a 15% decrease in generation costs throughout the course of the research. When ECED was assessed with a 15%–20% demand side management based restructured load demand model for the microgrid system, the generation costs were reduced even further.