Scientific Reports

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ISSN / EISSN : 2045-2322 / 2045-2322
Current Publisher: Springer Science and Business Media LLC (10.1038)
Total articles ≅ 120,659
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Priya Singh, Neeraj Bharti, Amar Pal Singh, Siddharth Kaushal Tripathi, Saurabh Prakash Pandey, Abhishek Singh Chauhan, Abhijeet Kulkarni, Aniruddha P. Sane
Scientific Reports, Volume 10, pp 1-16; doi:10.1038/s41598-020-74144-3

Abstract:
Flowers of fragrant roses such as Rosa bourboniana are ethylene-sensitive and undergo rapid petal abscission while hybrid roses show reduced ethylene sensitivity and delayed abscission. To understand the molecular mechanism underlying these differences, a comparative transcriptome of petal abscission zones (AZ) of 0 h and 8 h ethylene-treated flowers from R. bourboniana was performed. Differential regulation of 3700 genes (1518 up, 2182 down) representing 8.5% of the AZ transcriptome was observed between 0 and 8 h ethylene-treated R. bourboniana petal AZ. Abscission was associated with large scale up-regulation of the ethylene pathway but prominent suppression of the JA, auxin and light-regulated pathways. Regulatory genes encoding kinases/phosphatases/F-box proteins and transcription factors formed the major group undergoing differential regulation besides genes for transporters, wall modification, defense and phenylpropanoid pathways. Further comparisons with ethylene-treated petals of R. bourboniana and 8 h ethylene-treated AZ (R. hybrida) identified a core set of 255 genes uniquely regulated by ethylene in R. bourboniana AZ. Almost 23% of these encoded regulatory proteins largely conserved with Arabidopsis AZ components. Most of these were up-regulated while an entire set of photosystem genes was prominently down-regulated. The studies provide important information on regulation of petal abscission in roses.
Olatunde P. Olademehin, Chengyin Liu, Binayak Rimal, Nathaniel F. Adegboyega, Fu Chen, Cheolho Sim, Sung Joon Kim
Scientific Reports, Volume 10, pp 1-13; doi:10.1038/s41598-020-74292-6

Abstract:
Culex pipiens is a major carrier of the West Nile Virus, the leading cause of mosquito-borne disease in the continental United States. Cx. pipiens survive overwinter through diapause which is an important survival strategy that is under the control of insulin signaling and Foxo by regulating energy metabolism. Three homologous candidate genes, glycogen synthase (glys), atp-binding cassette transporter (atp), and low-density lipoprotein receptor chaperone (ldlr), that are under the regulation of Foxo transcription factor were identified in Cx. pipiens. To validate the gene functions, each candidate gene was silenced by injecting the target dsi-RNA to female Cx. pipiens during the early phase of diapause. The dsi-RNA injected diapause-destined female post-adult eclosion were fed for 7 days with 10% glucose containing 1% d-[13C6]glucose. The effects of dsi-RNA knockdown on glucose metabolism in intact mosquitoes were monitored using 13C solid-state NMR and ATR-FTIR. Our finding shows that the dsi-RNA knockdown of all three candidate genes suppressed glycogen and lipid biosyntheses resulting in inhibition of long-term carbon energy storage in diapausing females.
Maria Kaltenbrunner, Walter Mayer, Kirsten Kerkhoff, Rita Epp, Hermann Rüggeberg, Rupert Hochegger, Margit Cichna-Markl
Scientific Reports, Volume 10, pp 1-11; doi:10.1038/s41598-020-72655-7

Abstract:
Appropriate analytical methods are needed for the detection of food authentication. We investigated the applicability of a duplex real-time PCR assay targeting chromosome 1 and two singleplex real-time PCR assays targeting chromosome 9, both published recently, for the qualitative and quantitative determination of wild boar and domestic pig in processed food products. In addition, two singleplex real-time PCR assays targeting chromosome 7 were tested for their suitability to differentiate the two subspecies. Even by targeting the three genome loci, the probability of misclassification was not completely eliminated. Application of the real-time PCR assays to a total of 35 commercial meat products, including 22 goulash products, revealed that domestic pig DNA was frequently present, even in 14 out of 15 products declared to consist of 100% wild boar. Quantitative results obtained with the real-time PCR assays for wild boar (p < 0.001) and those for domestic pig (p < 0.001) were significantly different. However, the results obtained with the real-time PCR assays for wild boar (r = 0.673; p < 0.001) and those for domestic pig (r = 0.505; p = 0.002) were found to be significantly correlated. If the rules given in the paper are followed, the real-time PCR assays are applicable for routine analysis.
Akanksha Raj, Anuradha Venkatakrishnan Chimata, Amit Singh
Scientific Reports, Volume 10, pp 1-15; doi:10.1038/s41598-020-73891-7

Abstract:
The phenomenon of RNA polymerase II (Pol II) pausing at transcription start site (TSS) is one of the key rate-limiting steps in regulating genome-wide gene expression. In Drosophila embryo, Pol II pausing is known to regulate the developmental control genes expression, however, the functional implication of Pol II pausing during later developmental time windows remains largely unknown. A highly conserved zinc finger transcription factor, Motif 1 Binding Protein (M1BP), is known to orchestrate promoter-proximal pausing. We found a new role of M1BP in regulating Drosophila eye development. Downregulation of M1BP function suppresses eye fate resulting in a reduced eye or a “no-eye” phenotype. The eye suppression function of M1BP has no domain constraint in the developing eye. Downregulation of M1BP results in more than two-fold induction of wingless (wg) gene expression along with robust induction of Homothorax (Hth), a negative regulator of eye fate. The loss-of-eye phenotype of M1BP downregulation is dependent on Wg upregulation as downregulation of both M1BP and wg, by using wgRNAi, shows a significant rescue of a reduced eye or a “no-eye” phenotype, which is accompanied by normalizing of wg and hth expression levels in the eye imaginal disc. Ectopic induction of Wg is known to trigger developmental cell death. We found that upregulation of wg as a result of downregulation of M1BP also induces apoptotic cell death, which can be significantly restored by blocking caspase-mediated cell death. Our data strongly imply that transcriptional regulation of wg by Pol II pausing factor M1BP may be one of the important regulatory mechanism(s) during Drosophila eye development.
D. G. O’Neill, C. Pegram, P. Crocker, D. C. Brodbelt, D. B. Church, R. M. A. Packer
Scientific Reports, Volume 10, pp 1-13; doi:10.1038/s41598-020-73088-y

Abstract:
Brachycephalic dog breeds are regularly asserted as being less healthy than non-brachycephalic breeds. Using primary-care veterinary clinical data, this study aimed to identify predispositions and protections in brachycephalic dogs and explore differing inferences between univariable and multivariable results. All disorders during 2016 were extracted from a random sample of 22,333 dogs within the VetCompass Programme from a sampling frame of 955,554 dogs under UK veterinary care in 2016. Univariable and multivariable binary logistic regression modelling explored brachycephaly as a risk factor for each of a series of common disorders. Brachycephalic dogs were younger, lighter and less likely to be neutered than mesocephalic, dolichocephalic and crossbred dogs. Brachycephalic differed to non-brachycephalic types in their odds for 10/30 (33.33%) common disorders. Of these, brachycephalic types were predisposed for eight disorders and were protected for two disorders. Univariable and multivariable analyses generated differing inference for 11/30 (30.67%) disorders. This study provides strong evidence that brachycephalic breeds are generally less healthy than their non-brachycephalic counterparts. Results from studies that report only univariable methods should be treated with extreme caution due to potential confounding effects that have not been accounted for during univariable study design or analysis.
Cedric Joossen, Adrienn Baán, Carlos Moreno-Cinos, Jurgen Joossens, Nathalie Cools, Ellen Lanckacker, Lieve Moons, Kim Lemmens, Anne-Marie Lambeir, Erik Fransen, et al.
Scientific Reports, Volume 10, pp 1-14; doi:10.1038/s41598-020-74159-w

Abstract:
Dry eye syndrome (DES), a multifactorial disorder which leads to ocular discomfort, visual disturbance and tear film instability, has a rising prevalence and limited treatment options. In this study, a newly developed trypsin-like serine protease inhibitor (UAMC-00050) in a tear drop formulation was evaluated to treat ocular inflammation. A surgical animal model of dry eye was employed to investigate the potential of UAMC-00050 on dry eye pathology. Animals treated with UAMC-00050 displayed a significant reduction in ocular surface damage after evaluation with sodium fluorescein, compared to untreated, vehicle treated and cyclosporine-treated animals. The concentrations of IL-1α and TNF-α were also significantly reduced in tear fluid from UAMC-00050-treated rats. Additionally, inflammatory cell infiltration in the palpebral conjunctiva (CD3 and CD45), was substantially reduced. An accumulation of pro-MMP-9 and a decrease in active MMP-9 were found in tear fluid from animals treated with UAMC-00050, suggesting that trypsin-like serine proteases play a role in activating MMP-9 in ocular inflammation in this animal model. Comparative qRT-PCR analyses on ocular tissue indicated the upregulation of tryptase, urokinase plasminogen activator receptor (uPAR) and protease-activated receptor 2 (PAR2). The developed UAMC-00050 formulation was stable up to 6 months at room temperature in the absence of light, non-irritating and sterile with compatible pH and osmolarity. These results provide a proof-of-concept for the in vivo modifying potential of UAMC-00050 on dry eye pathology and suggest a central role of trypsin-like serine proteases and PAR2 in dry eye derived ocular inflammation.
Ryan T. Massopust, Young Il Lee, Anna L. Pritchard, Van-Khoa M. Nguyen, Dylan A. McCreedy, Wesley J. Thompson
Scientific Reports, Volume 10, pp 1-16; doi:10.1038/s41598-020-74192-9

Abstract:
The muscular dystrophy X-linked mouse (mdx) is the most commonly used preclinical model for Duchenne muscular dystrophy. Although disease progression in the mouse does not perfectly model the human disease, it shares many pathological features. Early characterizations of the model reported severe pathology through early adulthood followed by disease stabilization. As a result, research in the mdx mouse has largely focused on early adulthood. The overarching goal of this study is to improve the understanding of the mdx mouse model by tracking pathological features of the disease throughout life. We performed a thorough characterization of myofiber pathology in mdx mice from 2 weeks to 2 years of age. We report that individual mdx muscle fibers undergo progressive hypertrophy that continues through the lifespan. Despite massive hypertrophy on the myofiber level, we report no hypertrophy on the muscle level. These seemingly contradictory findings are explained by previously underappreciated myofiber loss in mdx mice. We conclude that due to myofiber loss, in combination with the progressive nature of other pathological features, aged mdx muscle tissue provides reliable benchmarks for disease progression that may be valuable in testing the efficacy of therapeutics for Duchenne muscular dystrophy.
Katelyn Arnold, YongMei Xu, Yi-En Liao, Brian C. Cooley, Rafal Pawlinski, Jian Liu
Scientific Reports, Volume 10, pp 1-10; doi:10.1038/s41598-020-74275-7

Abstract:
Heparan sulfate (HS) is a sulfated glycosaminoglycan abundant on the cell surface and in the extracellular matrix and has several biological activities including anticoagulation and anti-inflammation. Liver ischemia reperfusion injury is associated with coagulation and inflammatory responses. Here, we synthesized HS oligosaccharides with defined sulfation patterns and show that synthetic anticoagulant HS oligosaccharides limit liver ischemia reperfusion injury in a mouse model. Using a small targeted HS library, we demonstrate that an oligosaccharide that possesses both anticoagulant activity and binding affinity to HMGB1, the inflammatory target, decreases injury greater than oligosaccharides that only bind to HMGB1 or only have anticoagulant activity. HS oligosaccharides may represent a potential new therapeutic option for decreasing liver damage resulting from ischemia reperfusion injury.
Hua Yang, Kaishuo Zhang, Zi Liu, Tao Wang, Fan Shi, Jin Su, Jintao Zhang, Juanyue Liu, Li Dai
Scientific Reports, Volume 10, pp 1-8; doi:10.1038/s41598-020-74356-7

Abstract:
We aimed to provide evidence for radiotherapy treatment regimens in patients with clinically recurrent ovarian cancer. We analyzed the survival and prognostic factors in 43 patients who were treated for recurrent ovarian cancer at 58 tumor sites using three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) during January 2006–December 2017. t years 1, 2, and 3, overall survival (OS) rate was 82.4%, 68.4%, and 57.9%; local control (LC) rate was 100%, 100% and 80%; recurrence free survival (RFS) rate was 86.8%, 66.6%, and 61.1%; and disease-free survival (DFS) rate was 79.7%, 56.7%, and 46.8%, respectively. The radiotherapy technique was determined to be an independent prognostic factor for survival; the survival rate of patients was significantly improved with IMRT compared to 3D-CRT (P = 0.035). Radiotherapy dose was an independent prognostic factor; survival rate improved when patients were treated with a radiation dose ≥ 60 Gy as compared to < 60 Gy (P = 0.046). Elective nodal prophylactic radiation therapy (ENRT) did not lead to a significant improvement in survival when compared to involved-field radiation therapy (IFRT). The toxicities of 3D-CRT and IMRT were tolerable. One patient (2.3%) had grade 3 acute gastrointestinal (GI) toxicity, 2 (4.6%) grade 3 late GI toxicity, 5 (11.6%) grade 3 hematological toxicity, and 2 (4.6%) had grade 4 hematological toxicity. IMRT improved LC and OS in patients with recurrent ovarian cancer after surgery and multiple chemotherapy; toxicities were tolerable. The IMRT technique and radiotherapy dose of ≥ 60 Gy had independent prognostic significance for the survival of such patients.
Azadeh Mohtashamdolatshahi, Harald Kratz, Olaf Kosch, Ralf Hauptmann, Nicola Stolzenburg, Frank Wiekhorst, Ingolf Sack, Bernd Hamm, Matthias Taupitz, Jörg Schnorr
Scientific Reports, Volume 10, pp 1-9; doi:10.1038/s41598-020-74151-4

Abstract:
Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats’ tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3–MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (DL) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean DL ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of DL of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.
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