bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy
Authors: Wanior Marek , Krämer Andreas , Knapp Stefan , Joerger Andreas C. 
Published: May 2021

AbstractMulti-subunit ATPase-dependent chromatin remodelling complexes SWI/SNF (switch/sucrose non-fermentable) are fundamental epigenetic regulators of gene transcription. Functional genomic studies revealed a remarkable mutation prevalence of SWI/SNF-encoding genes in 20–25% of all human cancers, frequently driving oncogenic programmes. Some SWI/SNF-mutant cancers are hypersensitive to perturbations in other SWI/SNF subunits, regulatory proteins and distinct biological pathways, often resulting in sustained anticancer effects and synthetic lethal interactions. Exploiting these vulnerabilities is a promising therapeutic strategy. Here, we review the importance of SWI/SNF chromatin remodellers in gene regulation as well as mechanisms leading to assembly defects and their role in cancer development. We will focus in particular on emerging strategies for the targeted therapy of SWI/SNF-deficient cancers using chemical probes, including proteolysis targeting chimeras, to induce synthetic lethality.
The genome of the warm-season turfgrass African bermudagrass (Cynodon transvaalensis)
Authors: Cui Fengchao , Taier Geli , Li Manli , Dai Xiaoxia , Hang Nan , Zhang Xunzhong , Wang Xiangfeng , Wang Kehua 
Published: May 2021

Abstract
Cynodon species can be used for multiple purposes and have high economic and ecological significance. However, the genetic basis of the favorable agronomic traits of Cynodon species is poorly understood, partially due to the limited availability of genomic resources. In this study, we report a chromosome-scale genome assembly of a diploid Cynodon species, C. transvaalensis, obtained by combining Illumina and Nanopore sequencing, BioNano, and Hi-C. The assembly contains 282 scaffolds (~423.42 Mb, N50 = 5.37 Mb), which cover ~93.2% of the estimated genome of C. transvaalensis (~454.4 Mb). Furthermore, 90.48% of the scaffolds (~383.08 Mb) were anchored to nine pseudomolecules, of which the largest was 60.78 Mb in length. Evolutionary analysis along with transcriptome comparison provided a preliminary genomic basis for the adaptation of this species to tropical and/or subtropical climates, typically with dry summers. The genomic resources generated in this study will not only facilitate evolutionary studies of the Chloridoideae subfamily, in particular, the Cynodonteae tribe, but also facilitate functional genomic research and genetic breeding in Cynodon species for new leading turfgrass cultivars in the future.
Interaction of gibberellin and other hormones in almond anthers: phenotypic and physiological changes and transcriptomic reprogramming
Authors: Li Peng , Tian Jia , Guo Changkui , Luo Shuping , Li Jiang 
Published: May 2021

Abstract
Low temperature causes anther dysfunction, severe pollen sterility and, ultimately, major yield losses in crop plants. Previous studies have shown that the gibberellic acid (GA) metabolic pathway plays an important role in this process by regulating tapetum function and pollen development. However, the interaction mechanism of GA with other hormones mediating anther development is still unclear. Herein, we collected and analyzed almond (Amygdalus communis L.) anthers at the meiosis, tetrad, 1-nucleus, and mature 2-nucleus stages. The growth rate per 1000 anthers exhibited a significant positive correlation with the total bioactive GA compound content, and the levels of all bioactive GA compounds were highest in the 1-nucleus pollen stage. GA3 treatment experiments indicated that exogenous GA3 increased the levels of indole-3-acetic acid (IAA), trans-zeatin (tZ), and jasmonic acid (JA) and decreased the levels of salicylic acid (SA) and abscisic acid (ABA); moreover, GA3 improved pollen viability and quantities under cold conditions, whereas PP333 (paclobutrazol, an inhibitor of GA biosynthesis) was antagonistic with GA3 in controlling anther development. RNA-seq and qRT-PCR results showed that GA played an important role in anther development by regulating the expression of other phytohormone pathway genes, dehydration-responsive element-binding/C-repeat binding factor (DREB1/CBF)-mediated signaling genes, and anther development pathway genes. Our results reveal the novel finding that GA interacts with other hormones to balance anther development under normal- and low-temperature conditions in almond.
Underpinning the molecular programming attributing heat stress associated thermotolerance in tea (Camellia sinensis (L.) O. Kuntze)
Authors: Seth Romit , Maritim Tony Kipkoech , Parmar Rajni , Sharma Ram Kumar 
Published: May 2021

AbstractThe most daunting issue of global climate change is the deleterious impact of extreme temperatures on tea productivity and quality, which has resulted in a quest among researchers and growers. The current study aims to unravel molecular programming underpinning thermotolerance by characterizing heat tolerance and sensitivity response in 20 tea cultivars. The significantly higher negative influence of heat stress was recorded in a sensitive cultivar with reduced water retention (47%), chlorophyll content (33.79%), oxidation potential (32.48%), and increase in membrane damage (76.4%). Transcriptional profiling of most tolerant and sensitive cultivars identified 78 differentially expressed unigenes with chaperon domains, including low and high molecular weight heat shock protein (HSP) and heat shock transcription factors (HSFs) involved in heat shock response (HSR). Further, predicted transcriptional interactome network revealed their key role in thermotoleranceviawell-co-ordinated transcriptional regulation of aquaporins, starch metabolism, chlorophyll biosynthesis, calcium, and ethylene mediated plant signaling system. The study identified the key role of HSPs (CsHSP90) in regulating HSR in tea, wherein, structure-based molecular docking revealed the inhibitory role of geldanamycin (GDA) onCsHSP90 by blocking ATP binding site at N-terminal domain of predicted structure. Subsequently, GDA mediated leaf disc inhibitor assay further affirmed enhanced HSR with higher expression ofCsHSP17.6,CsHSP70, HSP101, andCsHSFA2 genes in tea. Through the current study, efforts were made to extrapolate a deeper understanding of chaperons mediated regulation of HSR attributing thermotolerance in tea.
CmMLO17 and its partner CmKIC potentially support Alternaria alternata growth in Chrysanthemum morifolium
Authors: Xin Jingjing , Liu Ye , Li Huiyun , Chen Sumei , Jiang Jiafu , Song Aiping , Fang Weimin , Chen Fadi 
Published: May 2021

AbstractTheMildew Resistance Locus O(MLO) gene family has been investigated in many species. However, there are few studies on chrysanthemumMLOgenes. We report in this study thatCmMLO17inChrysanthemum morifoliumwas upregulated afterAlternaria alternatainfection. Silencing ofCmMLO17by artificial microRNA resulted in reduced susceptibility of chrysanthemum toA. alternatainfection. Genes in the abscisic acid (ABA) and Ca2+signaling pathways were upregulated in theCmMLO17-silenced line R20 compared to the wild-type plants. We speculated thatCmMLO17-silenced plants had a faster and stronger defense response that was mediated by the ABA and Ca2+signaling pathways, resulting in reduced susceptibility of chrysanthemum toA. alternatainfection. In addition, a candidate gene,CmKIC, that may interact with CmMLO17 was discovered by the yeast two-hybrid assay. The interaction between CmMLO17 and CmKIC was confirmed using the yeast two-hybrid assay and bimolecular fluorescence complementation (BiFC) analysis. CmMLO17 and CmKIC were both located on the plasma membrane, and CmKIC was also located on the nucleus.CmKICoverexpression increased the susceptibility of chrysanthemum toA. alternata, whereasCmKICsilencing resulted in reduced susceptibility. Therefore, CmMLO17 and CmKIC may work together inC. morifoliumto support the growth ofA. alternata. The results of this study will provide insight into the potential function of MLO and improve the understanding of plant defense responses to necrotrophic pathogens.
Comparative transcriptomic analysis highlights contrasting levels of resistance of Vitis vinifera and Vitis amurensis to Botrytis cinerea
Authors: Wan Ran , Guo Chunlei , Hou Xiaoqing , Zhu Yanxun , Gao Min , Hu Xiaoyan , Zhang Songlin , Jiao Chen , Guo Rongrong , Li Zhi , Wang Xiping 
Published: May 2021

AbstractBotrytis cinereais a major grapevine (Vitisspp.) pathogen, but some genotypes differ in their degree of resistance. For example, theVitis viniferacultivar Red Globe (RG) is highly susceptible, butV. amurensisRupr Shuangyou (SY) is highly resistant. Here, we used RNA sequencing analysis to characterize the transcriptome responses of these two genotypes toB. cinereainoculation at an early infection stage. Approximately a quarter of the genes in RG presented significant changes in transcript levels during infection, the number of which was greater than that in the SY leaves. The genes differentially expressed between infected leaves of SY and RG included those associated with cell surface structure, oxidation, cell death and C/N metabolism. We found evidence that an imbalance in the levels of reactive oxygen species (ROS) and redox homeostasis probably contributed to the susceptibility of RG toB. cinerea. SY leaves had strong antioxidant capacities and improved ROS homeostasis following infection. Regulatory network prediction suggested that WRKY and MYB transcription factors are associated with the abscisic acid pathway. Weighted gene correlation network analysis highlighted preinfection features of SY that might contribute to its increased resistance. Moreover, overexpression ofVaWRKY10inArabidopsis thalianaandV. viniferaThompson Seedless enhanced resistance toB. cinerea. Collectively, our study provides a high-resolution view of the transcriptional changes of grapevine in response toB. cinereainfection and novel insights into the underlying resistance mechanisms.
Genetic analysis of the “head top shape” quality trait of Chinese cabbage and its association with rosette leaf variation
Authors: Sun Xiaoxue , Gao Ying , Lu Yin , Zhang Xiaomeng , Luo Shuangxia , Li Xing , Liu Mengyang , Feng Daling , Gu Aixia , Chen Xueping , Xuan Shuxin , Wang Yanhua , Shen Shuxing , Bonnema Guusje , Zhao Jianjun 
Published: May 2021

AbstractThe agricultural and consumer quality of Chinese cabbage is determined by its shape. The shape is defined by the folding of the heading leaves, which defines the head top shape (HTS). The overlapping HTS, in which the heading leaves curve inward and overlap at the top, is the shape preferred by consumers. To understand the genetic regulation of HTS, we generated a large segregating F2 population from a cross between pak choi and Chinese cabbage, with phenotypes ranging from nonheading to heading with either outward curving or inward curving overlapping heading leaves. HTS was correlated with plant height, outer/rosette leaf length, and petiole length. A high-density genetic map was constructed. Quantitative trait locus (QTL) analysis resulted in the identification of 22 QTLs for leafy head-related traits, which included five HTS QTLs. Bulked segregant analysis (BSA) was used to confirm HTS QTLs and identify candidate genes based on informative single-nucleotide polymorphisms. Interestingly, the HTS QTLs colocalized with QTLs for plant height, outer/rosette leaf, and petiole length, consistent with the observed phenotypic correlations. Combined QTL analysis and BSA laid a foundation for molecular marker-assisted breeding of Chinese cabbage HTS and directions for further research on the genetic regulation of this trait.
Co-located quantitative trait loci mediate resistance to Agrobacterium tumefaciens, Phytophthora cinnamomi, and P. pini in Juglans microcarpa × J. regia hybrids
Authors: Ramasamy Ramesh K. , Luo Ming-Cheng , Leslie Charles A. , Velasco Dianne , Ott Natalia , McClean Ali , Dandekar Abhaya M. , Aradhya Mallikarjuna , Brown Patrick J. , Browne Gregory T. , Kluepfel Daniel A. , Westphal Andreas , Dvorak Jan 
Published: May 2021

AbstractSoil-borne plant pathogens represent a serious threat that undermines commercial walnut (Juglans regia) production worldwide. Crown gall, caused byAgrobacterium tumefaciens, and Phytophthora root and crown rots, caused by variousPhytophthoraspp., are among the most devastating walnut soil-borne diseases. A recognized strategy to combat soil-borne diseases is adoption of resistant rootstocks. Here, resistance toA. tumefaciens, P. cinnamomi, andP. piniis mapped in the genome ofJuglans microcarpa, a North American wild relative of cultivated walnut. Half-sibJ. microcarpamother trees DJUG 31.01 and DJUG 31.09 were crossed withJ. regiacv. Serr, producing 353 and 400 hybrids, respectively. Clonally propagated hybrids were genotyped by sequencing to construct genetic maps for the two populations and challenged with the three pathogens. Resistance to each of the three pathogens was mapped as a major QTL on the long arm ofJ. microcarpachromosome 4D and was associated with the same haplotype, designated as haplotypeb, raising the possibility that the two mother trees were heterozygous for a single Mendelian gene conferring resistance to all three pathogens. The deployment of this haplotype in rootstock breeding will facilitate breeding of a walnut rootstock resistant to both crown gall and Phytophthora root and crown rots.
Genome-wide QTL analysis of tomato fruit cuticle deposition and composition
Authors: Barraj Barraj Rida , Segado Patricia , Moreno-González Rocío , Heredia Antonio , Fernández-Muñoz Rafael , Domínguez Eva 
Published: May 2021

AbstractGenetics of traits related to fruit cuticle deposition and composition was studied in two red-fruited tomato species. Two mapping populations derived from the cross between the cultivated tomato (Solanum lycopersicumL.) and its closest relative wild speciesSolanum pimpinellifoliumL. were employed to conduct a QTL analysis. A combination of fruit cuticle deposition, components and anatomical traits were investigated and the individual effect of each QTL evaluated. A total of 70 QTLs were identified, indicating that all the cuticle traits analyzed have a complex polygenic nature. A combination of additive and epistatic interactions was observed for all the traits, with positive contribution of both parental lines to most of them. Colocalization of QTLs for various traits uncovered novel genomic regions producing extensive changes in the cuticle. Cuticle density emerges as an important trait since it can modulate cuticle thickness and invagination thus providing a strategy for sustaining mechanical strength without compromising palatability. Two genomic regions, located in chromosomes 1 and 12, are responsible for the negative interaction between cuticle waxes and phenolics identified in tomato fruit. Several candidate genes, including transcription factors and structural genes, are postulated and their expression analyzed throughout development.
Whole-genome sequencing reveals rare off-target mutations in CRISPR/Cas9-edited grapevine
Authors: Wang Xianhang , Tu Mingxing , Wang Ya , Yin Wuchen , Zhang Yu , Wu Hongsong , Gu Yincong , Li Zhi , Xi Zhumei , Wang Xiping 
Published: May 2021

AbstractThe CRISPR (clustered regularly interspaced short palindromic repeats)-associated protein 9 (Cas9) system is a powerful tool for targeted genome editing, with applications that include plant biotechnology and functional genomics research. However, the specificity of Cas9 targeting is poorly investigated in many plant species, including fruit trees. To assess the off-target mutation rate in grapevine (Vitis vinifera), we performed whole-genome sequencing (WGS) of seven Cas9-edited grapevine plants in which one of two genes was targeted by CRISPR/Cas9 and three wild-type (WT) plants. In total, we identified between 202,008 and 272,397 single nucleotide polymorphisms (SNPs) and between 26,391 and 55,414 insertions/deletions (indels) in the seven Cas9-edited grapevine plants compared with the three WT plants. Subsequently, 3272 potential off-target sites were selected for further analysis. Only one off-target indel mutation was identified from the WGS data and validated by Sanger sequencing. In addition, we found 243 newly generated off-target sites caused by genetic variants between the Thompson Seedless cultivar and the grape reference genome (PN40024) but no true off-target mutations. In conclusion, we observed high specificity of CRISPR/Cas9 for genome editing of grapevine.
A cell surface-exposed protein complex with an essential virulence function in Ustilago maydis
Authors: Ludwig Nicole , Reissmann Stefanie , Schipper Kerstin , Gonzalez Carla , Assmann Daniela , Glatter Timo , Moretti Marino , Ma Lay-Sun , Rexer Karl-Heinz , Snetselaar Karen , Kahmann Regine 
Published: May 2021

AbstractPlant pathogenic fungi colonizing living plant tissue secrete a cocktail of effector proteins to suppress plant immunity and reprogramme host cells. Although many of these effectors function inside host cells, delivery systems used by pathogenic bacteria to translocate effectors into host cells have not been detected in fungi. Here, we show that five unrelated effectors and two membrane proteins from Ustilago maydis, a biotrophic fungus causing smut disease in corn, form a stable protein complex. All seven genes appear co-regulated and are only expressed during colonization. Single mutants arrest in the epidermal layer, fail to suppress host defence responses and fail to induce non-host resistance, two reactions that likely depend on translocated effectors. The complex is anchored in the fungal membrane, protrudes into host cells and likely contacts channel-forming plant plasma membrane proteins. Constitutive expression of all seven complex members resulted in a surface-exposed form in cultured U. maydis cells. As orthologues of the complex-forming proteins are conserved in smut fungi, the complex may become an interesting fungicide target.
Update Breast Cancer 2021 Part 2 – Advanced Stages, Long-Term Consequences and Biomarkers
Authors: Ditsch Nina , Stickeler Elmar , Behrens Annika , Belleville Erik , Fasching Peter A. , Fehm Tanja N. , Hartkopf Andreas D. , Jackisch Christian , Janni Wolfgang , Kolberg-Liedtke Cornelia , Kolberg Hans-Christian , Lüftner Diana , Lux Michael P. , Müller Volkmar , Schneeweiss Andreas , Schütz Florian , Schulmeyer Carla E. , Tesch Hans , Thomssen Christoph , Uleer Christoph , Untch Michael , Welslau Manfred , Wöckel Achim , Wurmthaler Lena A. , Würstlein Rachel , Thill Marc , Aktas Bahriye 
Published: May 2021

AbstractThis review summarises and discusses significant aspects of recently published studies on patient treatment in advanced breast cancer and on biomarkers in breast cancer. In recent years, a large number of drugs for all molecular subtypes have been developed up to phase III trials. With regard to immune checkpoint inhibitors in metastasised breast cancer, the recent discussion has centred on the best candidate for combined chemotherapy. The oral taxanes could become a new type of oral chemotherapies. There is a growing body of data on biomarkers for the use of CDK4/6 inhibitors, which could also signify further development for other molecular subtypes. New substances have been developed for metastatic HER2+ breast cancer that still result in good remission even after massive prior treatment and/or cerebral metastasis. Similarly, knowledge is growing about targeted therapies with antibody-drug conjugates (ADC) against Trop-2, which could bolster our therapeutic armoury in triple-negative breast cancer (TNBC). In addition, the clinical focus is on understanding how to maintain fertility after breast cancer treatment. Here, pooled analyses provide new insights.
Iron-Driven Alterations on Red Blood Cell-Derived Microvesicles Amplify Coagulation during Hemolysis via the Intrinsic Tenase Complex
Authors: Jongerius Ilse , Zeerleder Sacha S. , Delvasto-Núñez Laura , Roem Dorina , Bakhtiari Kamran , van Mierlo Gerard , Meijers Joost C. M. 
Published: May 2021

AbstractHemolytic disorders characterized by complement-mediated intravascular hemolysis, such as autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria, are often complicated by life-threatening thromboembolic complications. Severe hemolytic episodes result in the release of red blood cell (RBC)-derived proinflammatory and oxidatively reactive mediators (e.g., extracellular hemoglobin, heme, and iron) into plasma. Here, we studied the role of these hemolytic mediators in coagulation activation by measuring factor Xa (FXa) and thrombin generation in the presence of RBC lysates. Our results show that hemolytic microvesicles (HMVs) formed during hemolysis stimulate thrombin generation through a mechanism involving FVIII and FIX, the so-called intrinsic tenase complex. Iron scavenging during hemolysis using deferoxamine decreased the ability of the HMVs to enhance thrombin generation. Furthermore, the addition of ferric chloride (FeCl3) to plasma propagated thrombin generation in a FVIII- and FIX-dependent manner suggesting that iron positively affects blood coagulation. Phosphatidylserine (PS) blockade using lactadherin and iron chelation using deferoxamine reduced intrinsic tenase activity in a purified system containing HMVs as source of phospholipids confirming that both PS and iron ions contribute to the procoagulant effect of the HMVs. Finally, the effects of FeCl3 and HMVs decreased in the presence of ascorbate and glutathione indicating that oxidative stress plays a role in hypercoagulability. Overall, our results provide evidence for the contribution of iron ions derived from hemolytic RBCs to thrombin generation. These findings add to our understanding of the pathogenesis of thrombosis in hemolytic diseases.
Applications of Fecal Microbiota Transplantation: Emphasis on Clostridioides difficile Infections
Authors: Signorette Juliana Peloso , Oliveira Rômulo Tadeu Dias de , Montiel José Maria , Longo Priscila Larcher 
Published: May 2021

Abstract
Objective This study aimed to perform a comprehensive review of clinical trials using fecal microbiota transplantation in cases of Clostridioides difficile infection.
Methods This manuscript reviews clinical studies published from 2003 to 2020 at the Scientific Electronic Library Online (SciELO Brazil), Latin American and Caribbean Health Sciences Literature (LILACS) and US National Library of Medicine (MedLine/PubMed) databases using the descriptors antibiotic/antimicrobial, Clostridium difficile/Clostridioides difficile, intestinal microbiota/intestinal microbiome and fecal transplantation.
Results Interventions on microbiota include the use of probiotics, prebiotics, and fecal microbiota transplantation as therapeutic methods. Results show that fecal microbiota transplantation is an excellent alternative for the treatment of recurrent C. difficile infections.