bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered H3K27 trimethylation contributes to flowering time variations in polyploid Arabidopsis thaliana ecotypes
Authors: Cheng Jinping , Zhang Guiqian , Xu Linhao , Liu Chang , Jiang Hua 
Published: October 2021

Abstract
Polyploidy is a widespread phenomenon in flowering plant species. Polyploid plants frequently exhibit considerable transcriptomic alterations after whole-genome duplication (WGD). It is known that the transcriptomic response to tetraploidization is ecotype-dependent in Arabidopsis; however, the biological significance and the underlying mechanisms are unknown. In this study, we found that 4x Col-0 presents a delayed flowering time whereas 4x Ler does not. The expression of FLOWERING LOCUS C (FLC), the major repressor of flowering, was significantly increased in 4x Col-0 but only a subtle change was present in 4x Ler. Moreover, the level of a repressive epigenetic mark, trimethylation of histone H3 at lysine 27 (H3K27me3), was significantly decreased in 4x Col-0 but not in 4x Ler, potentially leading to the differences in FLC transcription levels and flowering times. Hundreds of other genes in addition to FLC showed H3K27me3 alterations in 4x Col-0 and 4x Ler. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) and transcription factors required for H3K27me3 deposition presented transcriptional changes between the two ecotypes, potentially accounting for the different H3K27me3 alterations. We also found that the natural 4x Arabidopsis ecotype Wa-1 presented an early flowering time, which was associated with low expression of FLC. Taken together, our results demonstrate a role of H3K27me3 alterations in response to genome duplication in Arabidopsis autopolyploids, and that variation in flowering time potentially functions in autopolyploid speciation.
Associations between ACE Genotypes, +8.5 Gz Tolerance, and Body Composition in F-15 Pilot Candidates
Authors: Shin Seunghwan , Son Seokhee 
Published: October 2021

ABSTRACT

Introduction
Pilots' +8.5Gz tolerance is related with their selection, safety and special mission suitability. The preliminary study about F-15 pilot candidates were rare, especially related with genetic effect like ACE (angiotensin converting enzyme) gene.

Background
This study aimed to investigate the associations between the +8.5 Gz test qualification and angiotensin converting enzyme (ACE) genotypes in Korean F-15 pilot candidates for pilot special mission suitability and cadet body composition education.

Materials and methods
We performed +8.5Gz test (15 seconds), target gene (ACE) identified and body composition measurements from twenty Korean F-15 pilot candidates (ages 23.0-28.6 years). The +8.5Gz test results (pass and not-passed), body composition parameters and their relationship with the ACE genotype were evaluated.

Results
Four (20%), six (30%), and 10 (50%) pilots had the DD, DI, and II genotypes based on the ACE gene identification results, respectively. Ten (50%) pilots passed by maintaining consciousness during the +Gz test. Of them, three (75%, 3/4), four (66.7%, 4/6), and three (30%, 3/10) had the DD, DI, and II genotypes (P &lt; .05, DD &gt; II), respectively. Compared with other genotypes, the DD genotype was associated with overall higher values of body composition indices, and this association was more prominent among pilots who passed the +8.5 Gz test.

Discussion
In some ethnic groups, the DD genotype has been found to have an effect on elite players’ high-intensity performance, including muscle power and strength. The DD genotype exhibited the highest performance in terms of passing rate, longest mean breathing interval(s), and higher values of body composition parameters in pilots who passed the +8.5 Gz test.

Conclusions
In this study, the group with the DD genotype exhibited a higher pass rate and heavier body composition parameters than the group with the II genotype. These results require further investigation to determine their significance and applicability in other ethnic groups.
Characterization of the metalloproteome of Pseudoalteromonas (BB2-AT2): biogeochemical underpinnings for zinc, manganese, cobalt, and nickel cycling in a ubiquitous marine heterotroph
Authors: Mazzotta Michael G , McIlvin Matthew R , Moran Dawn M , Wang David T , Bidle Kay D , Lamborg Carl H , Saito Mak A 
Published: October 2021

Abstract
Pseudoalteromonas (BB2-AT2) is a ubiquitous marine heterotroph, often associated with labile organic carbon sources in the ocean (e.g. phytoplankton blooms and sinking particles). Heterotrophs hydrolyze exported photosynthetic materials, components of the biological carbon pump, with the use of diverse metalloenzymes containing zinc (Zn), manganese (Mn), cobalt (Co), and nickel (Ni). Studies on the metal requirements and cytosolic utilization of metals for marine heterotrophs are scarce, despite their relevance to global carbon cycling. Here, we characterized the Zn, Mn, Co, and Ni metallome of BB2-AT2. We found that the Zn metallome is complex and cytosolic Zn is associated with numerous proteins for transcription (47.2% of the metallome, obtained from singular value decomposition of the metalloproteomic data), translation (33.5%), proteolysis (12.8%), and alkaline phosphatase activity (6.4%). Numerous proteolytic enzymes also appear to be putatively associated with Mn, and to a lesser extent, Co. Putative identification of the Ni-associated proteins, phosphoglucomutase and a protein in the cupin superfamily, provides new insights for Ni utilization in marine heterotrophs. BB2-AT2 relies on numerous transition metals for proteolytic and phosphatase activities, inferring an adaptative potential to metal limitation. Our field observations of increased alkaline phosphatase activity upon addition of Zn in field incubations suggest that such metal limitation operates in sinking particulate material collected from sediment traps. Taken together, this study improves our understanding of the Zn, Mn, Co, and Ni metallome of marine heterotrophic bacteria and provides novel and mechanistic frameworks for understanding the influence of nutrient limitation on biogeochemical cycling.
Multidimensional genome-wide screening in yeast provides mechanistic insights into europium toxicity
Authors: Pallares Roger M , An Dahlia D , Hébert Solène , Faulkner David , Loguinov Alex , Proctor Michael , Villalobos Jonathan A , Bjornstad Kathleen A , Rosen Chris J , Vulpe Christopher , Abergel Rebecca J 
Published: October 2021

AbstractEuropium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans. By using a multidimensional approach and functional and network analyses, we have identified a group of genes and proteins associated with the yeast responses to ameliorate metal toxicity, which include metal discharge paths through vesicle-mediated transport, paths to regulate biologically relevant cations, and processes to reduce metal-induced stress. Furthermore, the analyses indicated that europium promotes yeast toxicity by disrupting the function of chaperones and cochaperones, which have metal-binding sites. Several of the genes and proteins highlighted in our study have human orthologues, suggesting they may participate in europium-induced toxicity in humans. By identifying the endogenous targets of europium as well as the already existing paths that can decrease its toxicity, we can determine specific genes and proteins that may help to develop future therapeutic strategies.
Improved dsDNA recombineering enables versatile multiplex genome engineering of kilobase-scale sequences in diverse bacteria
Authors: Wang Xue , Zheng Wentao , Zhou Haibo , Tu Qiang , Tang Ya-Jie , Stewart A Francis , Zhang Youming , Bian Xiaoying 
Published: October 2021

Abstract
Recombineering assisted multiplex genome editing generally uses single-stranded oligonucleotides for site directed mutational changes. It has proven highly efficient for functional screens and to optimize microbial cell factories. However, this approach is limited to relatively small mutational changes. Here, we addressed the challenges involved in the use of double-stranded DNA substrates for multiplex genome engineering. Recombineering is mediated by phage single-strand annealing proteins annealing ssDNAs into the replication fork. We apply this insight to facilitate the generation of ssDNA from the dsDNA substrate and to alter the speed of replication by elevating the available deoxynucleoside triphosphate (dNTP) levels. Intracellular dNTP concentration was elevated by ribonucleotide reductase overexpression or dNTP addition to establish double-stranded DNA Recombineering-assisted Multiplex Genome Engineering (dReaMGE), which enables rapid and flexible insertional and deletional mutagenesis at multiple sites on kilobase scales in diverse bacteria without the generation of double-strand breaks or disturbance of the mismatch repair system. dReaMGE can achieve combinatorial genome engineering works, for example, alterations to multiple biosynthetic pathways, multiple promoter or gene insertions, variations of transcriptional regulator combinations, within a few days. dReaMGE adds to the repertoire of bacterial genome engineering to facilitate discovery, functional genomics, strain optimization and directed evolution of microbial cell factories.
Assessing genome-wide dynamic changes in enhancer activity during early mESC differentiation by FAIRE-STARR-seq
Authors: Glaser Laura V , Steiger Mara , Fuchs Alisa , van Bömmel Alena , Einfeldt Edda , Chung Ho-Ryun , Vingron Martin , Meijsing Sebastiaan H 
Published: October 2021

Abstract
Embryonic stem cells (ESCs) can differentiate into any given cell type and therefore represent a versatile model to study the link between gene regulation and differentiation. To quantitatively assess the dynamics of enhancer activity during the early stages of murine ESC differentiation, we analyzed accessible genomic regions using STARR-seq, a massively parallel reporter assay. This resulted in a genome-wide quantitative map of active mESC enhancers, in pluripotency and during the early stages of differentiation. We find that only a minority of accessible regions is active and that such regions are enriched near promoters, characterized by specific chromatin marks, enriched for distinct sequence motifs, and modeling shows that active regions can be predicted from sequence alone. Regions that change their activity upon retinoic acid-induced differentiation are more prevalent at distal intergenic regions when compared to constitutively active enhancers. Further, analysis of differentially active enhancers verified the contribution of individual TF motifs toward activity and inducibility as well as their role in regulating endogenous genes. Notably, the activity of retinoic acid receptor alpha (RARα) occupied regions can either increase or decrease upon the addition of its ligand, retinoic acid, with the direction of the change correlating with spacing and orientation of the RARα consensus motif and the co-occurrence of additional sequence motifs. Together, our genome-wide enhancer activity map elucidates features associated with enhancer activity levels, identifies regulatory regions disregarded by computational prediction tools, and provides a resource for future studies into regulatory elements in mESCs.
JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles
Authors: Castro-Mondragon Jaime A , Riudavets-Puig Rafael , Rauluseviciute Ieva , Berhanu Lemma Roza , Turchi Laura , Blanc-Mathieu Romain , Lucas Jeremy , Boddie Paul , Khan Aziz , Manosalva Pérez Nicolás , Fornes Oriol , Leung Tiffany Y , Aguirre Alejandro , Hammal Fayrouz , Schmelter Daniel , Baranasic Damir , Ballester Benoit , Sandelin Albin , Lenhard Boris , Vandepoele Klaas , Wasserman Wyeth W , Parcy François , Mathelier Anthony 
Published: October 2021

Abstract
JASPAR (http://jaspar.genereg.net/) is an open-access database containing manually curated, non-redundant transcription factor (TF) binding profiles for TFs across six taxonomic groups. In this 9th release, we expanded the CORE collection with 341 new profiles (148 for plants, 101 for vertebrates, 85 for urochordates, and 7 for insects), which corresponds to a 19% expansion over the previous release. We added 298 new profiles to the Unvalidated collection when no orthogonal evidence was found in the literature. All the profiles were clustered to provide familial binding profiles for each taxonomic group. Moreover, we revised the structural classification of DNA binding domains to consider plant-specific TFs. This release introduces word clouds to represent the scientific knowledge associated with each TF. We updated the genome tracks of TFBSs predicted with JASPAR profiles in eight organisms; the human and mouse TFBS predictions can be visualized as native tracks in the UCSC Genome Browser. Finally, we provide a new tool to perform JASPAR TFBS enrichment analysis in user-provided genomic regions. All the data is accessible through the JASPAR website, its associated RESTful API, the R/Bioconductor data package, and a new Python package, pyJASPAR, that facilitates serverless access to the data.
Inactivating transcription factorOsWRKY5enhances drought tolerance through abscisic acid signaling pathways
Authors: Lim Chaemyeong , Kang Kiyoon , Shim Yejin , Yoo Soo-Cheul , Paek Nam-Chon 
Published: October 2021

AbstractDuring crop cultivation, water-deficit conditions retard growth, thus reducing crop productivity. Therefore, uncovering the mechanisms behind drought tolerance is a critical task for crop improvement. Here, we show that the rice (Oryza sativa) WRKY transcription factor OsWRKY5 negatively regulates drought tolerance. We determined that OsWRKY5 was mainly expressed in developing leaves at the seedling and heading stages, and that its expression was reduced by drought stress and by treatment with NaCl, mannitol, and abscisic acid (ABA). Notably, the genome-edited loss-of-function alleles oswrky5-2 and oswrky5-3 conferred enhanced drought tolerance, measured as plant growth under water-deficit conditions. Conversely, the overexpression of OsWRKY5 in the activation-tagged line oswrky5-D resulted in higher susceptibility under the same conditions. The loss of OsWRKY5 activity increased sensitivity to ABA, thus promoting ABA-dependent stomatal closure. Transcriptome deep sequencing and reverse transcription quantitative polymerase chain reaction analyses demonstrated that the expression of abiotic stress-related genes including rice MYB2 (OsMYB2) was upregulated in oswrky5 knockout mutants and downregulated in oswrky5-D mutants. Moreover, dual-luciferase, yeast one-hybrid, and chromatin immunoprecipitation assays showed that OsWRKY5 directly binds to the W-box sequences in the promoter region of OsMYB2 and represses OsMYB2 expression, thus downregulating genes downstream of OsMYB2 in the ABA signaling pathways. Our results demonstrate that OsWRKY5 functions as a negative regulator of ABA-induced drought stress tolerance, strongly suggesting that inactivation of OsWRKY5 or manipulation of key OsWRKY5 targets could be useful to improve drought tolerance in rice cultivars.
Increasing loop flexibility affords low-temperature adaptation of a moderate thermophilic malate dehydrogenase from Geobacillus stearothermophilus
Authors: Shimozawa Yuya , Himiyama Tomoki , Nakamura Tsutomu , Nishiya Yoshiaki 
Published: October 2021

Abstract
Malate dehydrogenase (MDH) catalyzes the reversible reduction of nicotinamide adenine dinucleotide from oxaloacetate to L-malate. MDH from moderate thermophilic Geobacillus stearothermophilus (gs-MDH) has high thermal stability and substrate specificity and is used as a diagnostic reagent. In this study, gs-MDH was engineered to increase its catalytic activity at low temperatures. Based on sequential and structural comparison with lactate dehydrogenase from G. stearothermophilus, we selected G218 as a mutation site to increase the loop flexibility pivotal for MDH catalysis. The G218 mutants showed significantly higher specific activities than the wild type at low temperatures and maintained thermal stability. The crystal structure of the G218Y mutant, which had the highest catalytic efficiency among all the G218 mutants, suggested that the flexibility of the mobile loop was successfully increased by the bulky side chain. Therefore, this study demonstrated the low-temperature adaptation of MDH by facilitating conformational changes during catalysis.
Calcium silicate enhances immunosuppressive function of MSCs to indirectly modulate the polarization of macrophages
Authors: Li Haiyan , Wang Wenrui , Chang Jiang 
Published: October 2021

Abstract
Bioactive silicate ceramics (BSCs) have been widely reported to be able to induce bone tissue regeneration, but the underlying mechanisms have not been fully elucidated. Previous studies have reported that ionic products of BSCs can promote bone regeneration by directly simulating osteogenic differentiation of mesenchymal stem cells (MSCs) and modulating the polarization of macrophages to create a favorable inflammation microenvironment for initiating bone regeneration cascades. However, the immunomodulatory ability of MSCs also plays a critical role in bone regeneration but the effects of BSCs on the immunomodulatory ability of MSCs have been rarely investigated. This study aims to investigate the effects of ionic products of BSCs on the immunoregulatory ability of MSCs to further understand the mechanism of BSCs enhancing bone regeneration. Results showed that ionic products of calcium silicate (CS), one of the representative BSCs, could enhance the immunosuppressive function of human bone marrow mesenchymal stem cells (HBMSCs) by up-regulating the expression of immunosuppressive factors in HBMSCs via NF-κB pathway. In addition, CS-activated HBMSCs showed stronger stimulatory effects on M2 polarization of macrophages than CS ionic products. Furthermore, the macrophages educated by CS-activated HBMSCs showed stronger stimulatory effects on the early osteogenic differentiation of HBMSCs than the ones regulated by CS ionic products. These results not only provide further understanding on the mechanism of BSCs enhancing bone regeneration but also suggest that it is critical to consider the effects of biomaterials on the immunomodulatory function of the tissue forming cells when the immunomodulatory function of biomaterials is investigated.
Plasma exosomal RNAs have potential as both clinical biomarkers and therapeutic targets of dermatomyositis
Authors: Li Liya , Zuo Xiaoxia , Liu Di , Luo Hui , Zhang Huali , Peng Qinglin , Wang Guochun , Zhu Honglin 
Published: October 2021

Abstract

Objectives
DM is characterized by skeletal muscle weakness and cutaneous manifestations. Plasma exosomes (EXOs) contain proteins, RNAs, DNA, and lipid cargoes and are transferred among cells. If thoroughly investigated, plasma EXO RNAs could potentially improve our understanding of DM pathogenesis. We aimed to identify potential new biomarkers and therapeutic targets for DM.

Methods
The RNA (mRNA, miRNA and lncRNA) profiles of plasma EXOs were evaluated by sequencing on the Illumina HiSeq 3000 platform. Differentially expressed (DE) RNAs and bioinformatic analyses were performed. Human skeletal muscle myoblasts cells (HSkMCs) were stimulated with plasma EXOs, rapamycin or IFN-β. Real-time PCR and western blot analysis were used to detect related genes and proteins.

Results
A total of 689 DE mRNAs, 53 DE miRNAs and 452 DE lncRNAs were identified in DM plasma EXOs. Bioinformatic analysis inferred that plasma EXOs were secreted mainly by CD8+ T cells, regulatory T cells and natural killer cells. The DE miRNAs participated in the autophagy, TGF-β and Wnt signalling pathways. Three DE miRNAs (hsa-miR-125a-3p, hsa-miR-1246 and hsa-miR-3614-5p) were correlated with serological indices, organ involvement and myositis-specific autoantibodies. The DE lncRNAs participated in autophagy, IFN-β production and mTOR signalling. DM plasma EXOs can induce autophagy in HSkMCs by regulating three miRNAs (hsa-miR-125a-3p, hsa-miR-1246 and hsa-miR-3614-5p) and three lncRNAs (ENST00000584157.1, ENST00000523380.1 and ENST00000560054.1), which formed an autophagy network, playing a role in muscle damage.

Conclusion
Our study provides an overview of distinct RNA profiles in DM plasma EXOs, and verified some miRNAs as potential biomarkers and therapeutic targets. The findings provide important clues for more in-depth explorations of plasma EXOs in DM.
Global, regional and national trends in sex- and age-specific disability-adjusted life years of musculoskeletal disorders, 1990–2019
Authors: Jin Ziyi , Feng Xuebing , Wang Dandan , Zhu Yun , Liang Jun , Zhang Huayong , Zhao Jinkou , Sun Lingyun 
Published: October 2021

Abstract

Objective
To quantify the temporal trend of sex- and age-specific disability-adjusted life years (DALYs) for musculoskeletal (MSK) disorders by region and cause.

Methods
Data were collected from the Global Burden of Diseases Study 2019. The estimated annual percentage change (EAPC) by sex, age, region and cause was calculated to examine the temporal trend of the age-standardized DALYs rate (ASDR). The sociodemographic index (SDI) and risk exposures were also examined.

Results
Between 1990 and 2019, the global ASDR for MSK disorders remained almost stable by sex and age group but decreased among females ages 0–14 years (EAPC = −0.27). Such age and sex patterns were nearly the same by SDI, except for high SDI regions, where ASDR increased in all subgroups except those ages 15–49 years. The trend in ASDR of MSK disorders for females and males ages 50–74 and ≥75 years increased in ∼80% of countries and territories. The greatest increase was in El Salvador for males ages 15–49 years (EAPC = 1.30), followed by Nicaragua. The association between EAPC and SDI was positive in developing regions, particularly among females ages 15–49 years, and negative in developed regions. A decreasing trend in ASDR was mainly driven by the decrease in low back pain, while the increasing trend was largely due to other MSK disorders and gout across sexes and age groups.

Conclusions
There are great disparities in the age- and sex-specific trends in ASDR by cause on the global, regional and national levels. More differentiated prevention and management strategies are needed for MSK disorders.