bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health
Authors: Marttila Saara , Rovio Suvi , Mishra Pashupati P. , Seppälä Ilkka , Lyytikäinen Leo-Pekka , Juonala Markus , Waldenberger Melanie , Oksala Niku , Ala-Korpela Mika , Harville Emily , Hutri-Kähönen Nina , Kähönen Mika , Raitakari Olli , Lehtimäki Terho , Raitoharju Emma 
Published: April 2021

AbstractPreterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34–49 years, full-term n = 682, preterm n = 84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p = 1.90 × 10–4, FDR = 0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p = 0.002, fold change [FC] = − 1.20) and specifically in PTB subjects with small birthweight for gestational age (p = 0.095, FC = − 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism.
miRNA activity inferred from single cell mRNA expression
Authors: Nielsen Morten Muhlig , Pedersen Jakob Skou 
Published: April 2021

AbstractHigh throughput single-cell RNA sequencing (scRNAseq) can provide mRNA expression profiles for thousands of cells. However, miRNAs cannot currently be studied at the same scale. By exploiting that miRNAs bind well-defined sequence motifs and typically down-regulate target genes, we show that motif enrichment analysis can be used to derive miRNA activity estimates from scRNAseq data. Motif enrichment analyses have traditionally been used to derive binding motifs for regulatory factors, such as miRNAs or transcription factors, that have an effect on gene expression. Here we reverse its use. By starting from the miRNA seed site, we derive a measure of activity for miRNAs in single cells. We first establish the approach on a comprehensive set of bulk TCGA cancer samples (n = 9679), with paired mRNA and miRNA expression profiles, where many miRNAs show a strong correlation with measured expression. By downsampling we show that the method can be used to estimate miRNA activity in sparse data comparable to scRNAseq experiments. We then analyze a human and a mouse scRNAseq data set, and show that for several miRNA candidates, including liver specific miR-122 and muscle specific miR-1 and miR-133a, we obtain activity measures supported by the literature. The methods are implemented and made available in the miReact software. Our results demonstrate that miRNA activities can be estimated at the single cell level. This allows insights into the dynamics of miRNA activity across a range of fields where scRNAseq is applied.
Discovery, optimization, and evaluation of non-bile acid FXR/TGR5 dual agonists
Authors: Miyata Sachiho , Kawashima Yuji , Sakai Miku , Matsubayashi Masaya , Motoki Keisuke , Miyajima Yui , Watanabe Yousuke , Chikamatsu Noriko , Taniguchi Tetsuya , Tokuyama Ryukou 
Published: April 2021

AbstractAlthough several potent bile acid Farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1) dual agonists such as INT-767 have been reported, no non-bile acid FXR/TGR5 dual agonist has been investigated to date. Therefore, we attempted to discover potent non-bile acid FXR/TGR5 dual agonists and identified some non-bile acid FXR/TGR5 dual agonists, such as isonicotinamide derivatives in vitro assay. Compound 20p was evaluated in C57BL/6J mice, that were administered a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) consisting of 60 kcal% fat and 0.1% methionine by weight for one week. Compound 20p dose-dependently induced small heterodimer partner (SHP) mRNA and decreased cytochrome P450 7A1 (CYP7A1) in the liver at 10 and 30 mg/kg, respectively, which were used as FXR agonist markers. Compound 20p significantly increased the plasma levels of GLP-1 as a TGR5 agonist, and a high concentration of GLP-1 lowered blood glucose levels. We confirmed that compound 20p was a non-bile acid FXR/TGR5 dual agonist.
Temporal dynamics of viral load and false negative rate influence the levels of testing necessary to combat COVID-19 spread
Authors: Jarvis Katherine F. , Kelley Joshua B. 
Published: April 2021

AbstractColleges and other organizations are considering testing plans to return to operation as the COVID-19 pandemic continues. Pre-symptomatic spread and high false negative rates for testing may make it difficult to stop viral spread. Here, we develop a stochastic agent-based model of COVID-19 in a university sized population, considering the dynamics of both viral load and false negative rate of tests on the ability of testing to combat viral spread. Reported dynamics of SARS-CoV-2 can lead to an apparent false negative rate from ~ 17 to ~ 48%. Nonuniform distributions of viral load and false negative rate lead to higher requirements for frequency and fraction of population tested in order to bring the apparent Reproduction number (Rt) below 1. Thus, it is important to consider non-uniform dynamics of viral spread and false negative rate in order to model effective testing plans.
Multiscale analysis of the hydrate based carbon capture from gas mixtures containing carbon dioxide
Authors: Zhou Xuebing , Zang Xiaoya , Long Zhen , Liang Deqing 
Published: April 2021

AbstractTo reveal the kinetic performance of gas molecules in hydrate growth, hydrate formation from pure CO2, flue gas, and biogas was measured using in-situ Raman and macroscopic methods at 271.6 K. In the in-situ Raman measurements, Raman peaks of gases in the hydrate phase were characterised and normalised by taking the water bands from 2800 to 3800 cm−1 as a reference, whose line shapes were not found to have a noticeable change in the conversion from Ih ice to sI hydrate. The hydrate growth was suggested to start with the formation of unsaturated hydrate nuclei followed by gas adsorption. In hydrate formed from all tested gases, CO2 concentrations in hydrate nuclei were found to be 23–33% of the saturation state. In the flue gas system, the N2 concentration reached a saturation state once hydrate nuclei formed. In the biogas system, competitive adsorption of CH4 and CO2 molecules was observed, while N2 molecules hardly evolved in hydrate formation. Combined with micro- and macroscopic analysis, small molecules such as N2 and CO2 were suggested to be more active in the formation of hydrate nuclei, and the preferential adsorption of CO2 molecules took place in the subsequent gas adsorption process.
Prenatal transplantation of human amniotic fluid stem cell could improve clinical outcome of type III spinal muscular atrophy in mice
Authors: Shaw Steven W. , Peng Shao-Yu , Liang Ching-Chung , Lin Tzu-Yi , Cheng Po-Jen , Hsieh T’sang-T’ang , Chuang Hao-Yu , De Coppi Paolo , David Anna L. 
Published: April 2021

AbstractSpinal muscular atrophy (SMA) is a single gene disorder affecting motor function in uterus. Amniotic fluid is an alternative source of stem cell to ameliorate SMA. Therefore, this study aims to examine the therapeutic potential of Human amniotic fluid stem cell (hAFSC) for SMA. Our SMA model mice were generated by deletion of exon 7 of Smn gene and knock-in of human SMN2. A total of 16 SMA model mice were injected with 1 × 105 hAFSC in uterus, and the other 16 mice served as the negative control. Motor function was analyzed by three behavioral tests. Engraftment of hAFSC in organs were assessed by flow cytometry and RNA scope. Frequency of myocytes, neurons and innervated receptors were estimated by staining. With hAFSC transplantation, 15 fetuses survived (93.75% survival) and showed better performance in all motor function tests. Higher engraftment frequency were observed in muscle and liver. Besides, the muscle with hAFSC transplantation expressed much laminin α and PAX-7. Significantly higher frequency of myocytes, neurons and innervated receptors were observed. In our study, hAFSC engrafted on neuromuscular organs and improved cellular and behavioral outcomes of SMA model mice. This fetal therapy could preserve the time window and treat in the uterus.
Reproductive success of the parasitic mite (Varroa destructor) is lower in honeybee colonies that target infested cells with recapping
Authors: Oddie Melissa A. Y. , Burke Ashley , Dahle Bjørn , Le Conte Yves , Mondet Fanny , Locke Barbara 
Published: April 2021

AbstractCell recapping is a behavioural trait of honeybees (Apis mellifera) where cells with developing pupae are uncapped, inspected, and then recapped, without removing the pupae. The ectoparasitic mite Varroa destructor, unarguably the most destructive pest in apiculture world-wide, invades the cells of developing pupae to feed and reproduce. Honeybees that target mite infested cells with this behaviour may disrupt the reproductive cycle of the mite. Hence, cell recapping has been associated with colony-level declines in mite reproduction. In this study we compared the colony-level efficacy of cell recapping (how often infested cells are recapped) to the average mite fecundity in A. mellifera. Our study populations, known to be adapted to V. destructor, were from Avignon, France, Gotland, Sweden, and Oslo, Norway, and were compared to geographically similar, treated control colonies. The results show that colonies with a higher recapping efficacy also have a lower average mite reproductive success. This pattern was likely driven by the adapted populations as they had the largest proportion of highly-targeted cell recapping. The consistent presence of this trait in mite-resistant and mite-susceptible colonies with varying degrees of expression may make it a good proxy trait for selective breeding on a large scale.
Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms
Authors: Kato Shunsuke , Sato Takehiro , Fujita Hiroki , Kawatani Masahiro , Yamada Yuichiro 
Published: April 2021

AbstractThere is a close relationship between the gut microbiota and metabolic disorders. In this study, acute administration of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide to mice increased the cecal levels of caseinolytic protease B, a component of Escherichia coli, and of norepinephrine. Chemical sympathectomy blocked these events. Norepinephrine was found to pass into the intestinal lumen in vitro. c-Fos staining of the intermediolateral nucleus was identified as indirect evidence of sympathetic nervous system activation of the intestinal tract by GLP-1RA. Under normal conditions, the increase in E. coli did not affect the host. However, in mice with colitis, bacterial translocation was observed with attenuation of tight junction gene expression. This is the first study to investigate the unique underlying mechanisms related the effects of GLP-1RA on changes in the gut bacterium.
MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
Authors: Yeh Margaret , Wang Yin-Ying , Yoo Ji Young , Oh Christina , Otani Yoshihiro , Kang Jin Muk , Park Eun S. , Kim Eunhee , Chung Sangwoon , Jeon Young-Jun , Calin George A. , Kaur Balveen , Zhao Zhongming , Lee Tae Jin 
Published: April 2021

AbstractTumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one of the significantly downregulated miRNAs with an inverse correlation with CD44 expression. Transient overexpression of miR-138 in GBM cells inhibited cell proliferation, cell cycle, migration, and wound healing capability. We unveiled that miR-138 negatively regulates the expression of CD44 by directly binding to the 3′ UTR of CD44. CD44 inhibition by miR-138 resulted in an inhibition of glioblastoma cell proliferation in vitro through cell cycle arrest as evidenced by a significant induction of p27 and its translocation into nucleus. Ectopic expression of miR-138 also increased survival rates in mice that had an intracranial xenograft tumor derived from human patient-derived primary GBM cells. In conclusion, we demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 for the treatment of primary GBM.
Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
Authors: Murray Jonathan B. , Mikhael Christy , Han Guanghong , de Faria Lorraine Perciliano , Rody Wellington J. , Holliday L. Shannon 
Published: April 2021

AbstractThe (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H+-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the “handle region peptide” from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.
Importance of Angomonas deanei KAP4 for kDNA arrangement, cell division and maintenance of the host-bacterium relationship
Authors: Gonçalves Camila Silva , Catta-Preta Carolina Moura Costa , Repolês Bruno , Mottram Jeremy C. , De Souza Wanderley , Machado Carlos Renato , Motta Maria Cristina M. 
Published: April 2021

AbstractAngomonas deanei coevolves in a mutualistic relationship with a symbiotic bacterium that divides in synchronicity with other host cell structures. Trypanosomatid mitochondrial DNA is contained in the kinetoplast and is composed of thousands of interlocked DNA circles (kDNA). The arrangement of kDNA is related to the presence of histone-like proteins, known as KAPs (kinetoplast-associated proteins), that neutralize the negatively charged kDNA, thereby affecting the activity of mitochondrial enzymes involved in replication, transcription and repair. In this study, CRISPR-Cas9 was used to delete both alleles of the A. deanei KAP4 gene. Gene-deficient mutants exhibited high compaction of the kDNA network and displayed atypical phenotypes, such as the appearance of a filamentous symbionts, cells containing two nuclei and one kinetoplast, and division blocks. Treatment with cisplatin and UV showed that Δkap4 null mutants were not more sensitive to DNA damage and repair than wild-type cells. Notably, lesions caused by these genotoxic agents in the mitochondrial DNA could be repaired, suggesting that the kDNA in the kinetoplast of trypanosomatids has unique repair mechanisms. Taken together, our data indicate that although KAP4 is not an essential protein, it plays important roles in kDNA arrangement and replication, as well as in the maintenance of symbiosis.
Regulatory role of non-coding RNA in ginseng rusty root symptom tissue
Authors: Bian Xingbo , Yu Pengcheng , Dong Ling , Zhao Yan , Yang He , Han Yongzhong , Zhang Lianxue 
Published: April 2021

AbstractGinseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.
Investigating the status of transgenic crops in Iran in terms of cultivation, consumption, laws and rights in comparison with the world
Authors: Baghbani-Arani Abolfazl , Poureisa Mona , Alekajbaf Hossein , Borz-Abad Rezvan Karami , Khodadadi-Dashtaki Khodadad 
Published: April 2021

AbstractRecently, there has been a development in transgenic technologies in many countries to meet nutritional needs of increasing worlds҆ population. However, there are some concerns about possible risks in the field of growing genetically modified (GM) food, such as threats of biodiversity and food allergies making their use a challenge. Therefore, the present study was conducted to investigate the economic effects and political scopes of GM foods in production sector and policies made by different countries in the world and Iran. Moreover, essential (practical and legal) solutions and guidelines were provided for production and consumption of GM foods, which are useful for governmental entities, Iranian politicians, and consumers' rights. The latest situation of transgenic crops in the countries with which Iran has the highest exchange of agricultural products (including Turkey, Pakistan, and the European Union (EU)) was also studied. Although, Iran has been one of leading Asian countries not only in the field of transfer of technical knowledge of genetic engineering, but also in development of the specialized knowledge of biosafety, and despite production of several transgenic plant lines by Iranian researchers, unfortunately no GM crop has obtained release and cultivation license except for GM rice that its growing process was banned after change of government. According to findings of this study, in Iran, growing and production process of GM crops does not follow the global trend owing to scientific and legal infrastructures.
Hybrid Raman-erbium random fiber laser with a half open cavity assisted by artificially controlled backscattering fiber reflectors
Authors: Perez-Herrera R. A. , Roldan-Varona P. , Galarza M. , Sañudo-Lasagabaster S. , Rodriguez-Cobo L. , Lopez-Higuera J. M. , Lopez-Amo M. 
Published: April 2021

AbstractA hybrid Raman-erbium random fiber laser with a half-open cavity assisted by chirped artificially controlled backscattering fiber reflectors is presented. A combination of a 2.4 km-long dispersion compensating fiber with two highly erbium-doped fiber pieces of 5 m length were used as gain media. A single random laser emission line centered at 1553.8 nm with an optical signal to noise ratio of 47 dB were obtained when pumped at 37.5 dBm. A full width at half maximum of 1 nm and a 100% confidence level output power instability as low as 0.08 dB were measured. The utilization of the new laser cavity as a temperature and strain sensor is also experimentally studied.
Development of a highly specific serodiagnostic ELISA for West Nile virus infection using subviral particles
Authors: Maezono Keisuke , Kobayashi Shintaro , Tabata Koshiro , Yoshii Kentaro , Kariwa Hiroaki 
Published: April 2021

AbstractWest Nile virus (WNV), a member of the Japanese encephalitis virus (JEV) serocomplex group, causes lethal encephalitis in humans and horses. Because serodiagnosis of WNV and JEV is hampered by cross-reactivity, the development of a simple, secure, and WNV-specific serodiagnostic system is required. The coexpression of prM protein and E protein leads to the secretion of subviral particles (SPs). Deletion of the C-terminal region of E protein is reported to affect the production of SPs by some flaviviruses. However, the influence of such a deletion on the properties and antigenicity of WNV E protein is unclear. We analyzed the properties of full-length E protein and E proteins lacking the C-terminal region as novel serodiagnostics for WNV infection. Deletion of the C-terminal region of E protein suppressed the formation of SPs but did not affect the production of E protein. The sensitivity of an enzyme-linked immunosorbent assay (ELISA) using the full-length E protein was higher than that using the truncated E proteins. Furthermore, in the ELISA using full-length E protein, there was little cross-reactivity with anti-JEV antibodies, and the sensitivity was similar to that of the neutralization test.
A new role of Yb3+—an energy reservoir for lanthanide upconversion luminescence
Authors: Xu Li , Liu Yu , Zhou Ziwen , Sun Xianhao , Ud Din Isam , Khan Fahim , Li Yanzeng , Li Hanyang , Ren Jing , Carvajal Joan J. , Zhang Jianzhong , Liu Lu 
Published: April 2021

We proposed a novel energy cycling mechanism by introducing Yb3+ as an energy reservoir to improve the Ln3+ upconversion intensity. The key of the energy cycling mechanism is suppressing the energy dissipation and/or facilitating the ESA population.