bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analyses of the microbiological, immunological and ontological transitions in the calf ileum during early life
Authors: Lyons Tamsin , Jahns Hanne , Brady Joseph , O’Hara Eóin , Waters Sinéad M. , Kenny David , Doyle Evelyn , Meade Kieran G. 
Published: December 2020

AbstractAberdeen Angus calves were sacrificed from immediately post-birth up to 96 days of age (DOA) and ileal samples were collected for microbial, histological and immunological analyses.Firmicutesbacteria were established immediately in the ileum of calves after birth and remained the dominant phyla at all time points from birth until 96 DOA. Temporal shifts in phyla reflected significantly increasedBacteroidetesat birth followed by temporal increases inActinobacteriaabundance over time. At a cellular level, a significant increase in cell density was detected in the ileal villi over time. The innate cell compartment at birth was composed primarily of eosinophils and macrophages with a low proportion of adaptive T lymphocytes; whereas an increase in the relative abundance of T cells (including those in the intra-epithelial layer) was observed over time. The ileal intestinal cells were immunologically competent as assessed by expression levels of genes encoding the inflammasome sensorNLRP3, and inflammatory cytokinesIL1A,IL1BandIL33—all of which significantly increased from birth. In contrast, a temporal reduction in genes encoding anti-inflammatory cytokineIL10was detected from birth. This study provides an integrated baseline of microbiological, histological and immunological data on the immune adaptation of the neonatal ileum to microbial colonisation in calves.
Extremely large third-order nonlinear optical effects caused by electron transport in quantum plasmonic metasurfaces with subnanometer gaps
Authors: Takeuchi Takashi , Yabana Kazuhiro 
Published: December 2020

AbstractIn this study, a third-order nonlinear optical responses in quantum plasmonic metasurfaces composed of metallic nano-objects with subnanometer gaps were investigated using time-dependent density functional theory, a fully quantum mechanical approach. At gap distances of ≥ 0.6 nm, the third-order nonlinearities monotonically increased as the gap distance decreased, owing to enhancement of the induced charge densities at the gaps between nano-objects. Particularly, when the third harmonic generation overlapped with the plasmon resonance, a large third-order nonlinearity was achieved. At smaller gap distances down to 0.1 nm, we observed the appearance of extremely large third-order nonlinearity without the assistance of the plasmon resonance. At a gap distance of 0.1 nm, the observed third-order nonlinearity was approximately three orders of magnitude larger than that seen at longer gap distances. The extremely large third-order nonlinearities were found to originate from electron transport by quantum tunneling and/or overbarrier currents through the subnanometer gaps.
Serotonin receptor 5-HT7 in Drosophila mushroom body neurons mediates larval appetitive olfactory learning
Authors: Ganguly Archan , Qi Cheng , Bajaj Jeevisha , Lee Daewoo 
Published: December 2020

AbstractSerotonin (5-HT) and dopamine are critical neuromodulators known to regulate a range of behaviors in invertebrates and mammals, such as learning and memory. Effects of both serotonin and dopamine are mediated largely through their downstream G-protein coupled receptors through cAMP-PKA signaling. While the role of dopamine in olfactory learning inDrosophilais well described, the function of serotonin and its downstream receptors onDrosophilaolfactory learning remain largely unexplored. In this study we show that the output of serotonergic neurons, possibly through points of synaptic contacts on the mushroom body (MB), is essential for training during olfactory associative learning inDrosophilalarvae. Additionally, we demonstrate that the regulation of olfactory associative learning by serotonin is mediated by its downstream receptor (d5-HT7) in a cAMP-dependent manner. We show that d5-HT7 expression specifically in the MB, an anatomical structure essential for olfactory learning inDrosophila,is critical for olfactory associative learning. Importantly our work shows that spatio-temporal restriction of d5-HT7 expression to the MB is sufficient to rescue olfactory learning deficits in a d5-HT7 null larvae. In summary, our results establish a critical, and previously unknown, role of d5-HT7 in olfactory learning.
Wireless, miniaturized, semi-implantable electrocorticography microsystem validated in vivo
Authors: Keramatzadeh Keivan , Kiakojouri Ali , Nahvi Mohammad Sadegh , Khazaei Yousef , Feizi-nejad Ali , Maghami Mohammad Hossein , Mohammadi Reza , Sharifshazileh Mohammadali , Nasiri Soraya , Akbari Boroumand Farhad , Nadimi Ebrahim , Rezaei Mahmoud , Shojaei Amir , Mirnajafi-Zadeh Javad , Sodagar Amir M. 
Published: December 2020

AbstractThis paper reports on the design, development, and test of a multi-channel wireless micro-electrocorticography (µECoG) system. The system consists of a semi-implantable, ultra-compact recording unit and an external unit, interfaced through a 2.4 GHz radio frequency data telemetry link with 2 Mbps (partially used) data transfer rate. Encased in a 3D-printed 2.9 cm × 2.9 cm × 2.5 cm cubic package, the semi-implantable recording unit consists of a microelectrode array, a vertically-stacked PCB platform containing off-the-shelf components, and commercially-available small-size 3.7-V, 50 mAh lithium-ion batteries. Two versions of microelectrode array were developed for the recording unit: a rigid 4 × 2 microelectrode array, and a flexible 12 × 6 microelectrode array, 36 of which routed to bonding pads for actual recording. The external unit comprises a transceiver board, a data acquisition board, and a host computer, on which reconstruction of the received signals is performed. After development, assembly, and integration, the system was tested and validated in vivo on anesthetized rats. The system successfully recorded both spontaneous and evoked activities from the brain of the subject.
Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver
Authors: Kawahori Kenichi , Kondo Yoshitaka , Yuan Xunmei , Kawasaki Yuki , Hanzawa Nozomi , Tsujimoto Kazutaka , Wada Fumiko , Kohda Takashi , Ishigami Akihito , Yamada Tetsuya , Ogawa Yoshihiro , Hashimoto Koshi 
Published: December 2020

AbstractAscorbic acid (AA, vitamin C) serves as a cofactor for ten-eleven translocation (TET) enzymes and induces DNA demethylation in vitro. However, its role in DNA demethylation in vivo remains unclear. We previously reported that DNA demethylation in the mouse liver was enhanced during the suckling period. Therefore, we hypothesized that DNA demethylation is enhanced in an AA-dependent manner during the suckling period. To examine our hypothesis, we employed wild-type (WT) mice, which synthesize AA, and senescence marker protein-30/gluconolactonase (SMP30/GNL) knockout (KO) mice, which cannot synthesize AA, and analyzed the DNA methylation status in the livers of offspring in both the suckling period and adulthood. SMP30/GNL KO offspring showed DNA hypermethylation in the liver possibly due to low plasma and hepatic AA levels during the suckling period despite the administration of rescue-dose AA to dams. Furthermore, DNA hypermethylation of the fibroblast growth factor 21 gene (Fgf21), a PPARα target gene, persisted into adulthood. In contrast, a high-dose AA administration to SMP30/GNL KO dams during the lactation period restored DNA demethylation in the livers of offspring. Even though a slight increase was observed in plasma AA levels with the administration of rescue-dose AA to WT dams during the gestation and lactation periods, DNA demethylation in the livers of offspring was minimally enhanced. The present results demonstrate that AA intake during the suckling period is required for proper DNA demethylation in the liver.
Mismatch of thermal optima between performance measures, life stages and species of spiny lobster
Authors: Twiname Samantha , Fitzgibbon Quinn P. , Hobday Alistair J. , Carter Chris G. , Oellermann Michael , Pecl Gretta T. 
Published: December 2020

AbstractIn an ocean warming hotspot off south-east Australia, many species have expanded their ranges polewards, including the eastern rock lobster,Sagmariasus verreauxi. This species is likely extending its range via larval advection into Tasmanian coastal waters, which are occupied by the more commercially important southern rock lobster,Jasus edwardsii. Here, thermal tolerances of these lobster species at two life stages were investigated to assess how they may respond to warming ocean temperatures. We found that the pattern, optimum and magnitude of thermal responses differed between performance measures, life stages and species.Sagmariasus verreauxihad a warmer optimal temperature for aerobic scope and escape speed thanJ. edwardsii. However,J. edwardsiihad a higher magnitude of escape speed, indicating higher capacity for escape performance. There were also differences between life stages within species, with the larval stage having higher variation in optimal temperatures between measures than juveniles. This inconsistency in performance optima and magnitude indicates that single performance measures at single life stages are unlikely to accurately predict whole animal performance in terms of life-time survival and fitness. However, combined results of this study suggest that with continued ocean warming,S. verreauxiis likely to continue to extend its distribution polewards and increase in abundance in Tasmania.
Neural bases for attenuation of morphine withdrawal by Heantos-4: role of l-tetrahydropalmatine
Authors: Ahn Soyon , Nesbit Maya O. , Zou Haiyan , Vacca Giada , Axerio-Cilies Peter , Van Sung Tran , Phillips Anthony G. 
Published: December 2020

AbstractSevere withdrawal symptoms triggered by cessation of long-term opioid use deter many individuals from seeking treatment. Opioid substitution and α2-adrenergic agonists are the current standard of pharmacotherapy for opioid use disorder in western medicine; however, each is associated with significant complications. Heantos-4 is a non-opioid botanical formulation used to facilitate opioid detoxification in Vietnam. While ongoing clinical use continues to validate its safety and effectiveness, a mechanism of action accounting for these promising effects remains to be specified. Here, we assess the effects of Heantos-4 in a rat model of morphine-dependence and present evidence that alleviation of naloxone-precipitated somatic withdrawal signs is related to an upregulation of mesolimbic dopamine activity and a consequent reversal of a hypodopaminergic state in the nucleus accumbens, a brain region implicated in opioid withdrawal. A central dopaminergic mechanism is further supported by the identification of l-tetrahydropalmatine as a key active ingredient in Heantos-4, which crosses the blood–brain barrier and shows a therapeutic efficacy comparable to its parent formulation in attenuating withdrawal signs. The anti-hypodopaminergic effects of l-tetrahydropalmatine may be related to antagonism of the dopamine autoreceptor, thus constituting a plausible mechanism contributing to the effectiveness of Heantos-4 in facilitating opioid detoxification.
DNA methyltransferase 3B plays a protective role against hepatocarcinogenesis caused by chronic inflammation via maintaining mitochondrial homeostasis
Authors: Iguchi Eriko , Takai Atsushi , Takeda Haruhiko , Kumagai Ken , Arasawa Soichi , Eso Yuji , Shimizu Takahiro , Ueda Yoshihide , Marusawa Hiroyuki , Seno Hiroshi 
Published: December 2020

AbstractMost hepatocellular carcinomas (HCCs) develop on the basis of chronic hepatitis, but the mechanism of epigenetic regulation in inflammatory hepatocarcinogenesis has yet to be elucidated. Among de novo DNA methyltransferases (DNMTs), DNMT3B has lately been reported to act specifically on actively transcribed genes, suggesting the possibility that it plays a role in the pathogenesis of cancer. We confirmed that DNMT3B isoforms lacking its catalytic domain were highly expressed in HCCs compared with non-tumorous liver tissue. To elucidate the role of DNMT3B in hepatocarcinogenesis, we generated a genetically engineered mouse model with hepatocyte-specific Dnmt3b deletion. The liver of the Dnmt3b-deficient mice exhibited an exacerbation of thioacetamide-induced hepatitis, progression of liver fibrosis and a higher incidence of HCC compared with the liver of the control mice. Whole-genome bisulfite sequencing verified a lower CG methylation level in the Dnmt3b-deficient liver, demonstrating differentially methylated regions throughout the genome. Transcriptome analysis revealed decreased expression of genes related to oxidative phosphorylation in the Dnmt3b-deficient liver. Moreover, primary hepatocytes isolated from the Dnmt3b-deficient mice showed reduced mitochondrial respiratory capacity, leading to the enhancement of oxidative stress in the liver tissue. Our findings suggest the protective role of DNMT3B against chronic inflammation and HCC development via maintaining mitochondrial homeostasis.
Positioning of an unprecedented spiro[5.5]undeca ring system into kinase inhibitor space
Authors: Venkanna Arramshetti , Subedi Lalita , Teli Mahesh K. , Lama Prema Dhorma , Nangunuri Bhargav Gupta , Lee Sang-Yoon , Kim Sun Yeou , Kim Mi-hyun 
Published: December 2020

AbstractIn-house 1,5-oxaza spiroquinone 1, with spiro[5.5]undeca ring system, was announced as an unprecedented anti-inflammatory scaffold through chemistry-oriented synthesis (ChOS), a chemocentric approach. Herein, we studied how to best position the spiro[5.5]undeca ring system in kinase inhibitor space. Notably, late-stage modification of the scaffold 1 into compounds 2a-r enhanced kinase-likeness of the scaffold 1. The improvement could be depicted with (1) selectivity with target shift (from JNK-1 into GSK-3) and (2) potency (> 20-fold). In addition, ATP independent IC50 of compound 2j suggested a unique binding mode of this scaffold between ATP site and substrate site, which was explained by docking based optimal site selection and molecular dynamic simulations of the optimal binding site. Despite the shift of kinase profiling, the anti-inflammatory activity of compounds 2a-r could be retained in hyperactivated microglial cells.
Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis
Authors: Giedraitiene N. , Kizlaitiene R. , Peceliunas V. , Griskevicius L. , Kaubrys G. 
Published: December 2020

AbstractThe aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients—during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed.
Gastrointestinal adenocarcinoma analysis identifies promoter methylation-based cancer subtypes and signatures
Authors: Xiang Renshen , Fu Tao 
Published: December 2020

AbstractGastric adenocarcinoma (GAC) and colon adenocarcinoma (CAC) are the most common gastrointestinal cancer subtypes, with a high incidence and mortality. Numerous studies have shown that its occurrence and progression are significantly related to abnormal DNA methylation, especially CpG island methylation. However, little is known about the application of DNA methylation in GAC and CAC. The methylation profiles were accessed from the Cancer Genome Atlas database to identify promoter methylation-based cancer subtypes and signatures for GAC and CAC. Six hypo-methylated clusters for GAC and six hyper-methylated clusters for CAC were separately generated with different OS profiles, tumor progression became worse as the methylation level decreased in GAC or increased in CAC, and hypomethylation in GAC and hypermethylation in CAC were negatively correlated with microsatellite instability. Additionally, the hypo- and hyper-methylated site-based signatures with high accuracy, high efficiency and strong independence can separately predict the OS of GAC and CAC patients. By integrating the methylation-based signatures with prognosis-related clinicopathologic characteristics, two clinicopathologic-epigenetic nomograms were cautiously established with strong predictive performance and high accuracy. Our research indicates that methylation mechanisms differ between GAC and CAC, and provides novel clinical biomarkers for the diagnosis and treatment of GAC and CAC.
High-throughput screening to discover inhibitors of the CarD·RNA polymerase protein–protein interaction in Mycobacterium tuberculosis
Authors: Stefan Maxwell A. , Velazquez Glory M. , Garcia George A. 
Published: December 2020

AbstractMultidrug-resistant Mycobacterium tuberculosis (MDR-TB) accounts for 3.7% of new cases of TB annually worldwide and is a major threat to global public health. Due to the prevalence of the MDR-TB and extensively drug resistant tuberculosis (XDR-TB) cases, there is an urgent need for new drugs with novel mechanisms of action. CarD, a global transcription regulator in MTB, binds RNAP and activates transcription by stabilizing the transcription initiation open-promoter complex (RPo). CarD is required for MTB viability and it has highly conserved homologues in many eubacteria. A fluorescence polarization (FP) assay which monitors the association of MTB RNAP, native rRNA promoter DNA and CarD has been developed. Overall, our objective is to identify and characterize small molecule inhibitors which block the CarD/RNAP interaction and to understand the mechanisms by which CarD interacts with the molecules. We expect that the development of a new and improved anti-TB compound with a novel mechanism of action will relieve the burden of resistance. This CarD FP assay is amenable to HTS and is an enabling tool for future novel therapeutic discovery.
Abiotic stressors impact outer membrane vesicle composition in a beneficial rhizobacterium: Raman spectroscopy characterization
Authors: Potter Matthew , Hanson Cynthia , Anderson Anne J. , Vargis Elizabeth , Britt David W. 
Published: December 2020

AbstractOuter membrane vesicles (OMVs) produced by Gram-negative bacteria have roles in cell-to-cell signaling, biofilm formation, and stress responses. Here, the effects of abiotic stressors on OMV contents and composition from biofilm cells of the plant health-promoting bacterium Pseudomonas chlororaphis O6 (PcO6) are examined. Two stressors relevant to this root-colonizing bacterium were examined: CuO nanoparticles (NPs)-a potential fertilizer and fungicide- and H2O2-released from roots during plant stress responses. Atomic force microscopy revealed 40–300 nm diameter OMVs from control and stressed biofilm cells. Raman spectroscopy with linear discriminant analysis (LDA) was used to identify changes in chemical profiles of PcO6 cells and resultant OMVs according to the cellular stressor with 84.7% and 83.3% accuracies, respectively. All OMVs had higher relative concentrations of proteins, lipids, and nucleic acids than PcO6 cells. The nucleic acid concentration in OMVs exhibited a cellular stressor-dependent increase: CuO NP-induced OMVs > H2O2-induced OMVs > control OMVs. Biochemical assays confirmed the presence of lipopolysaccharides, nucleic acids, and protein in OMVs; however, these assays did not discriminate OMV composition according to the cellular stressor. These results demonstrate the sensitivity of Raman spectroscopy using LDA to characterize and distinguish cellular stress effects on OMVs composition and contents.
Radiological screening of maternal periodontitis for predicting adverse pregnancy and neonatal outcomes
Authors: Heo Ju Sun , Ahn Ki Hoon , Park Jung Soo 
Published: December 2020

AbstractIt is well known that periodontitis, diagnosed mainly by periodontal probing, is associated with adverse pregnancy outcomes. However, periodontal probing is time-consuming, highly discomforting, inaccurate, and invasive. We aimed to assess whether periodontitis severity based on radiological staging in accordance with the 2017 new consensus classification was related to adverse pregnancy and neonatal outcomes. The medical records of 165 mothers who underwent panoramic radiography within 5 years before and after the time of delivery and of their singleton neonates were retrospectively reviewed. Twenty-two mothers (13.3%) had severe periodontitis (SP), and 143 (86.7%) had mild or moderate periodontitis (MP). In relation to adverse pregnancy outcomes, uterine leiomyoma (18.2% vs. 4.2%,P = 0.029), chronic hypertension (9.1% vs. 0.7%,P = 0.047), and preeclampsia (13.6% vs. 2.1%,P = 0.032) occurred significantly more frequently in the SP group than in the MP group. The incidences of very preterm birth (13.6% vs. 1.4%,P = 0.017), extremely preterm birth (9.1% vs. 0.7%,P = 0.047), and small for gestational age (22.7% vs. 5.6%,P = 0.017) were also significantly higher in the SP group than in the MP group. Radiological screening of maternal periodontitis could be useful for predicting adverse pregnancy and neonatal outcomes as well as diagnosing SP in pregnant women.