bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced maternal age perturbs mouse embryo development and alters the phenotype of derived embryonic stem cells
Authors: Khurana Pooja , Smyth Neil R. , Sheth Bhavwanti , Velazquez Miguel A. , Eckert Judith J. , Fleming Tom P. 
Published: July 2021

AbstractAdvanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos. Young (7–8 weeks) and Old (7–8 months) C57BL/6 female mice were mated with young males. Preimplantation embryos from Old dams displayed developmental retardation in blastocyst morphogenesis. mESC lines established from these blastocysts using conventional techniques revealed differences in genetic, cellular and molecular criteria conserved over several passages in the standardised medium. mESCs from embryos from AMA dams displayed increased incidence of aneuploidy following Giemsa karyotyping compared with those from Young dams. Moreover, AMA caused an altered pattern of expression of pluripotency markers (Sox2, OCT4) in mESCs. AMA further diminished mESC survival and proliferation and reduced the expression of cell proliferation marker, Ki-67. These changes coincided with altered expression of the epigenetic marker, Dnmt3a and other developmental regulators in a sex-dependent manner. Collectively, our data demonstrate the feasibility to utilise mESCs to reveal developmental mechanisms underlying AMA in the absence of maternal senescence and with reduced animal use.
Identification of a paraquat-resistant goosegrass (Eleusine indica) population from a central Alabama vegetable production field
Authors: McElroy J. Scott , Harris James R. , Price Andrew , Harkess Alex , Li Xiao 
Published: July 2021

AbstractA goosegrass [Eleusine indica (L.) Gaertn.] population uncontrolled by paraquat (R) in a vegetable production field in St. Clair County, AL, was collected in summer 2019. Research was conducted to assess the level of resistance of the suspected resistant population compared with three populations with no suspected paraquat resistance (S1, S2, and S3). Visual injury at all rating dates and biomass reduction at 28 d after treatment (DAT) of S populations occurred exponentially to increasing paraquat rates. S biotypes were injured more than R at 3 DAT, with biomass recovery at 28 DAT only occurring at rates <0.28 kg ha−1. Plant death or biomass reduction did not occur for any rate at any date for R. Paraquat rates that induced 50% or 90% injury or reduced biomass 50% or 90% compared with the non-treated (I50 or I90, respectively) ranged from 10 to 124 times higher I50 for R compared with S and 54 to 116 times higher I90 for R compared with S biotypes. These data confirm a paraquat-resistant E. indica biotype in Alabama, providing additional germplasm for study of resistance to photosystem I electron-diverting (PSI-ED) resistance mechanisms.
Mitigating Prediction Error of Deep Learning Streamflow Models in Large Data‐Sparse Regions With Ensemble Modeling and Soft Data
Authors: Feng Dapeng , Lawson Kathryn , Shen Chaopeng 
Published: July 2021

AbstractPredicting discharge in contiguously data‐scarce or ungauged regions is needed for quantifying the global hydrologic cycle. We show that prediction in ungauged regions (PUR) has major, underrecognized uncertainty and is drastically more difficult than previous problems where basins can be represented by neighboring or similar basins (known as prediction in ungauged basins). While deep neural networks demonstrated stellar performance for streamflow predictions, performance nonetheless declined for PUR, benchmarked here with a new stringent region‐based holdout test on a US data set with 671 basins. We tested approaches to reduce such errors, leveraging deep network's flexibility to integrate “soft” data, such as satellite‐based soil moisture product, or daily flow distributions which improved low flow simulations. A novel input‐selection ensemble improved average performance and greatly reduced catastrophic failures. Despite challenges, deep networks showed stronger performance metrics for PUR than traditional hydrologic models. They appear competitive for geoscientific modeling even in data‐scarce settings.
Hyperoside promotes pollen tube growth by regulating the depolymerization effect of actin-depolymerizing factor 1 on microfilaments in okra
Authors: Dong Biying , Yang Qing , Song Zhihua , Niu Lili , Cao Hongyan , Liu Tengyue , Du Tingting , Yang Wanlong , Qi Meng , Chen Ting , Wang Mengying , Jin Haojie , Meng Dong , Fu Yujie 
Published: July 2021

AbstractMature pollen germinates rapidly on the stigma, extending its pollen tube to deliver sperm cells to the ovule for fertilization. The success of this process is an important factor that limits output. The flavonoid content increased significantly during pollen germination and pollen tube growth, which suggests it may play an important role in these processes. However, the specific mechanism of this involvement has been little researched. Our previous research found that hyperoside can prolong the flowering period of Abelmoschus esculentus (okra), but its specific mechanism is still unclear. Therefore, in this study, we focused on the effect of hyperoside in regulating the actin-depolymerizing factor (ADF), which further affects the germination and growth of pollen. We found that hyperoside can prolong the effective pollination period of okra by 2–3-fold and promote the growth of pollen tubes in the style. Then, we used Nicotiana benthamiana cells as a research system and found that hyperoside accelerates the depolymerization of intercellular microfilaments. Hyperoside can promote pollen germination and pollen tube elongation in vitro. Moreover, AeADF1 was identified out of all AeADF genes as being highly expressed in pollen tubes in response to hyperoside. In addition, hyperoside promoted AeADF1-mediated microfilament dissipation according to microfilament severing experiments in vitro. In the pollen tube, the gene expression of AeADF1 was reduced to 1/5 by oligonucleotide transfection. The decrease in the expression level of AeADF1 partially reduced the promoting effect of hyperoside on pollen germination and pollen tube growth. This research provides new research directions for flavonoids in reproductive development.
An efficient papaya leaf distortion mosaic potyvirus vector for virus-induced gene silencing in papaya
Authors: Tuo Decai , Yan Pu , Zhao Guangyuan , Cui Hongguang , Zhu Guopeng , Liu Yang , Yang Xiukun , Wang He , Li Xiaoying , Shen Wentao , Zhou Peng 
Published: July 2021

AbstractPapaya (Carica papaya L.) is regarded as an excellent model for genomic studies of tropical trees because of its short generation time and its small genome that has been sequenced. However, functional genomic studies in papaya depend on laborious genetic transformations because no rapid tools exist for this species. Here, we developed a highly efficient virus-induced gene silencing (VIGS) vector for use in papaya by modifying an artificially attenuated infectious clone of papaya leaf distortion mosaic virus (PLDMV; genus: Potyvirus), PLDMV-E, into a stable Nimble Cloning (NC)-based PLDMV vector, pPLDMV-NC, in Escherichia coli. The target fragments for gene silencing can easily be cloned into pPLDMV-NC without multiple digestion and ligation steps. Using this PLDMV VIGS system, we silenced and characterized five endogenous genes in papaya, including two common VIGS marker genes, namely, phytoene desaturase, Mg-chelatase H subunit, putative GIBBERELLIN (GA)-INSENSITIVE DWARF1A and 1B encoding GA receptors; and the cytochrome P450 gene CYP83B1, which encodes a key enzyme involved in benzylglucosinolate biosynthesis. The results demonstrate that our newly developed PLDMV VIGS vector is a rapid and convenient tool for functional genomic studies in papaya.
EjBZR1 represses fruit enlargement by binding to the EjCYP90 promoter in loquat
Authors: Su Wenbing , Shao Zikun , Wang Man , Gan Xiaoqing , Yang Xianghui , Lin Shunquan 
Published: July 2021

Abstract
Loquat (Eriobotrya japonica) is a subtropical tree that bears fruit that ripens during late spring. Fruit size is one of the dominant factors inhibiting the large-scale production of this fruit crop. To date, little is known about fruit size regulation. In this study, we first discovered that cell size is more important to fruit size than cell number in loquat and that the expression of the EjBZR1 gene is negatively correlated with cell and fruit size. Virus-induced gene silencing (VIGS) of EjBZR1 led to larger cells and fruits in loquat, while its overexpression reduced cell and plant size in Arabidopsis. Moreover, both the suppression and overexpression of EjBZR1 inhibited the expression of brassinosteroid (BR) biosynthesis genes, especially that of EjCYP90A. Further experiments indicated that EjCYP90A, a cytochrome P450 gene, is a fruit growth activator, while EjBZR1 binds to the BRRE (CGTGTG) motif of the EjCYP90A promoter to repress its expression and fruit cell enlargement. Overall, our results demonstrate a possible pathway by which EjBZR1 directly targets EjCYP90A and thereby affects BR biosynthesis, which influences cell expansion and, consequently, fruit size. These findings help to elucidate the molecular functions of BZR1 in fruit growth and thus highlight a useful genetic improvement that can lead to increased crop yields by repressing gene expression.
Glandular trichomes: new focus on horticultural crops
Authors: Feng Zhongxuan , Bartholomew Ezra S. , Liu Ziyu , Cui Yuanyuan , Dong Yuming , Li Sen , Wu Haoying , Ren Huazhong , Liu Xingwang 
Published: July 2021

AbstractPlant glandular trichomes (GTs) are epidermal outgrowths with the capacity to biosynthesize and secrete specialized metabolites, that are of great scientific and practical significance. Our understanding of the developmental process of GTs is limited, and no single plant species serves as a unique model. Here, we review the genetic mechanisms of GT initiation and development and provide a summary of the biosynthetic pathways of GT-specialized metabolites in nonmodel plant species, especially horticultural crops. We discuss the morphology and classification of GT types. Moreover, we highlight technological advancements in methods employed for investigating GTs. Understanding the molecular basis of GT development and specialized metabolites not only offers useful avenues for research in plant breeding that will lead to the improved production of desirable metabolites, but also provides insights for plant epidermal development research.
A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease
Authors: Pedersen Camilla Christina , Lange Johannes , Førland Marthe Gurine Gunnarsdatter , Macleod Angus D. , Alves Guido , Maple-Grødem Jodi 
Published: July 2021

AbstractThere is great heterogeneity in both the clinical presentation and rate of disease progression among patients with Parkinson’s disease (PD). This can pose prognostic difficulties in a clinical setting, and a greater understanding of the risk factors that contribute to modify disease course is of clear importance for optimizing patient care and clinical trial design. Genetic variants in SNCA are an established risk factor for PD and are candidates to modify disease presentation and progression. This systematic review aimed to summarize all available primary research reporting the association of SNCA polymorphisms with features of PD. We systematically searched PubMed and Web of Science, from inception to 1 June 2020, for studies evaluating the association of common SNCA variants with age at onset (AAO) or any clinical feature attributed to PD in patients with idiopathic PD. Fifty-eight studies were included in the review that investigated the association between SNCA polymorphisms and a broad range of outcomes, including motor and cognitive impairment, sleep disorders, mental health, hyposmia, or AAO. The most reproducible findings were with the REP1 polymorphism or rs356219 and an earlier AAO, but no clear associations were identified with an SNCA polymorphism and any individual clinical outcome. The results of this comprehensive summary suggest that, while there is evidence that genetic variance in the SNCA region may have a small impact on clinical outcomes in PD, the mechanisms underlying the association of SNCA polymorphisms with PD risk may not be a major factor driving clinical heterogeneity in PD.
The interindividual variability of sleep timing and circadian phase in humans is influenced by daytime and evening light conditions
Authors: Papatsimpa C. , Schlangen L. J. M. , Smolders K. C. H. J. , Linnartz J.-P. M. G. , de Kort Y. A. W. 
Published: July 2021

AbstractHuman cognitive functioning shows circadian variations throughout the day. However, individuals largely differ in their timing during the day of when they are more capable of performing specific tasks and when they prefer to sleep. These interindividual differences in preferred temporal organization of sleep and daytime activities define the chronotype. Since a late chronotype is associated with adverse mental and physical consequences, it is of vital importance to study how lighting environments affect chronotype. Here, we use a mathematical model of the human circadian pacemaker to understand how light in the built environment changes the chronotype distribution in the population. In line with experimental findings, we show that when individuals spend their days in relatively dim light conditions, this not only results in a later phase of their biological clock but also increases interindividual differences in circadian phase angle of entrainment and preferred sleep timing. Increasing daytime illuminance results in a more narrow distribution of sleep timing and circadian phase, and this effect is more pronounced for longer photoperiods. The model results demonstrate that modern lifestyle changes the chronotype distribution towards more eveningness and more extreme differences in eveningness. Such model-based predictions can be used to design guidelines for workplace lighting that help limiting circadian phase differences, and craft new lighting strategies that support human performance, health and wellbeing.
Canagliflozin protects against sepsis capillary leak syndrome by activating endothelial α1AMPK
Authors: Angé Marine , De Poortere Julien , Ginion Audrey , Battault Sylvain , Dechamps Mélanie , Muccioli Giulio G. , Roumain Martin , Morelle Johann , Druart Sébastien , Mathivet Thomas , Bertrand Luc , Castanares-Zapatero Diego , Horman Sandrine , Beauloye Christophe 
Published: July 2021

AbstractSepsis capillary leak syndrome (SCLS) is an independent prognostic factor for poor sepsis outcome. We previously demonstrated that α1AMP-activated protein kinase (α1AMPK) prevents sepsis-induced vascular hyperpermeability by mechanisms involving VE-cadherin (VE-Cad) stabilization and activation of p38 mitogen activated protein kinase/heat shock protein of 27 kDa (p38MAPK/HSP27) pathway. Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, has recently been proven to activate AMPK in endothelial cells. Therefore, we hypothesized that canagliflozin could be of therapeutic potential in patients suffering from SCLS. We herein report that canagliflozin, used at clinically relevant concentrations, counteracts lipopolysaccharide-induced vascular hyperpermeability and albumin leakage in wild-type, but not in endothelial-specific α1AMPK-knockout mice. In vitro, canagliflozin was demonstrated to activate α1AMPK/p38MAPK/HSP27 pathway and to preserve VE-Cad’s integrity in human endothelial cells exposed to human septic plasma. In conclusion, our data demonstrate that canagliflozin protects against SCLS via an α1AMPK-dependent pathway, and lead us to consider novel therapeutic perspectives for this drug in SCLS.
Prognostic and predictive value of ALDH1, SOX2 and SSEA-4 in bladder cancer
Authors: Blomqvist Matias , Koskinen Ilmari , Löyttyniemi Eliisa , Mirtti Tuomas , Boström Peter J. , Taimen Pekka 
Published: July 2021

AbstractTransurethral resection of bladder tumor (TUR-BT) and radical cystectomy (RC) are standard treatment options for bladder cancer (BC). Neoadjuvant chemotherapy (NAC) prior to RC improves outcome of some patients but currently there are no valid biomarkers to identify patients who benefit from NAC. Presence of cancer stem cells (CSC) has been associated with poor outcome and resistance to chemotherapy in various cancers. Here we studied the expression of stem cell markers ALDH1, SOX2 and SSEA-4 with immunohistochemistry in tissue microarray material consisting of 195 BC patients treated with RC and 74 patients treated with TUR-BT followed by NAC and RC. Post-operative follow-up data of up to 22 years was used. Negative to weak cytoplasmic SOX2 staining was associated with lymphovascular invasion and non-organ confined disease. It was also associated with shortened cancer-specific survival, but the finding was not statistically significant. Contrary to previous reports, none of the other tested biomarkers were associated with cancer-specific mortality or clinicopathological characteristics. Neither were they associated with response to NAC. Despite the promising results of previously published studies, our results suggest that CSC markers ALDH1, SOX2 and SSEA-4 have little if any prognostic or predictive value in BC treated with RC.
A comprehensive transcriptomic landscape of cholangiocarcinoma based on bioinformatics analysis from large cohort of patients
Authors: Li Hongguang , Qu Lingxin , Zhang Haibin , Liu Jun , Zhang Xiaolu 
Published: July 2021

AbstractCholangiocarcinoma (CCA) is a group of malignancies emerging in the biliary tree and is associated with a poor patient prognosis. Although the anatomical location is the only worldwide accepted classification basis, it still has bias. The current study integrates the whole-genome expression data from several big cohorts in the literature, to screen and provide a comprehensive bioinformatic analysis, in order to better classify molecular subtypes and explore an underlying cluster mechanism related to anatomy and geographical regions. Differentially expressed protein-coding genes (DEGs) were identified for CCA as well as subtypes. Biological function enrichment analysis—Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis—was applied and identified different DEGs enriched signaling pathways in CCA subtypes. A co-expression network was presented by Weighted gene co-expression network analysis package and modules related to specific phenotypes were identified. Combined with DEGs, hub genes in the given module were demonstrated through protein–protein interaction network analysis. Finally, DEGs which significantly related to patient overall survival and disease-free survival time were selected, including ARHGAP21, SCP2, UBIAD1, TJP2, RAP1A and HDAC9.
Prostasin regulates PD-L1 expression in human lung cancer cells
Authors: Chen Li-Mei , Chai Julius C , Liu Bin , Strutt Tara M , McKinstry K Kai , Chai Karl X 
Published: July 2021

The serine protease prostasin is a negative regulator of lipopolysaccharide-induced inflammation and has a role in the regulation of cellular immunity. Prostasin expression in cancer cells inhibits migration and metastasis, and reduces epithelial-mesenchymal transition. Programmed death-ligand 1 (PD-L1) is a negative regulator of the immune response and its expression in cancer cells interferes with immune surveillance. The aim of this study was to investigate if prostasin regulates PD-L1 expression. We established sublines over-expressing various forms of prostasin as well as a subline deficient for the prostasin gene from the Calu-3 human lung cancer cells. We report here that PD-L1 expression induced by interferon-gamma (IFNg) is further enhanced in cells over-expressing the wild-type membrane-anchored prostasin. The PD-L1 protein was localized on the cell surface and released into the culture medium in extracellular vesicles (EVs) with the protease-active prostasin. The epidermal growth factor-epidermal growth factor receptor (EGF-EGFR), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK) participated in the prostasin-mediated up-regulation of PD-L1 expression. A Gene Set Enrichment Analysis (GSEA) of patient lung tumors in The Cancer Genome Atlas (TCGA) database revealed that prostasin and PD-L1 regulate common signaling pathways during tumorigenesis and tumor progression.
New Antimycotics in the Pipeline – For Ophthalmology Too?
Authors: Behrens-Baumann Wolfgang J. 
Published: July 2021

AbstractSeven new antimycotics are presented that are at different points of development or approval. These substances are mainly first-in-class drugs. They are primarily developed for systemic administration. However, with the support of a pharmacist, the intravenous formulation may be used as eyedrops. In this short review, the activities of the substances against various fungal infections are described. After unsuccessful conventional therapy of fungal eye infections, one of these new substances might be suitable to cure the mycosis.
A study into hawler botanical garden (h.b.g) in comparison to some other botanical gardens of the world
Authors: Kareem Kardo N. , Maulood Bahram K. 
Published: July 2021

Abstract
The aim of establishing botanical garden (B.G) in any place, has now been well expanded. It is confined to creation of an aesthetically pleasant refuge form of life as perfect as possible. In fact, it is an outdoor and indoor living museum of plant. Recently it becomes a multi-purpose area in contrast to any traditional gardens, park or greenery. However, such, botanical garden is not found in Iraq and it is almost not available in whole Middle East countries. The present project is a first attempt to establish a botanical garden under the name of Hawler botanical garden (H.B.G) in Iraq. Its structure, design and composition are forwarded and discussed in the present paper. However, (H.B.G) goal is planned to be extended for creation of a herbarium, seed bank, gene bank, conservation of energy, also country local specific gardens and especially Kurdish gardens, all of which are not exist or found so far in the area. Undoubtedly, this will encourage establishing more such gardens in the region in order to increase greenery area and refresh the environment.