bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full rescue of an inactive olfactory receptor mutant by elimination of an allosteric ligand-gating site
Authors: Sharma Kanika , Balfanz Sabine , Baumann Arnd , Korsching Sigrun 
Published: June 2018

AbstractLigand-gating has recently been proposed as a novel mechanism to regulate olfactory receptor sensitivity. TAAR13c, the zebrafish olfactory receptor activated by the death-associated odor cadaverine, appears to possess an allosteric binding site for cadaverine, which was assumed to block progress of the ligand towards the internal orthosteric binding-and-activation site. Here we have challenged the suggested gating mechanism by modeling the entry tunnel for the ligand as well as the ligand path inside the receptor. We report an entry tunnel, whose opening is blocked by occupation of the external binding site by cadaverine, confirming the hypothesized gating mechanism. A multistep docking algorithm suggested a plausible path for cadaverine from the allosteric to the orthosteric binding-and-activation site. Furthermore we have combined a gain-of-function gating site mutation and a loss-of-function internal binding site mutation in one recombinant receptor. This receptor had almost wildtype ligand affinities, consistent with modeling results that showed localized effects for each mutation. A novel mutation of the suggested gating site resulted in increased receptor ligand affinity. In summary both the experimental and the modeling results provide further evidence for the proposed gating mechanism, which surprisingly exhibits pronounced similarity to processes described for some metabotropic neurotransmitter receptors.
The Joint Association of Small for Gestational Age and Nighttime Sleep with Blood Pressure in Childhood
Authors: Wang Hongjian , Mueller Noel , Wang Guoying , Hong Xiumei , Chen Ting , Ji Yuelong , Pearson Colleen , Appel Lawrence J. , Wang Xiaobin 
Published: June 2018

AbstractChildren born small for gestational age (SGA) are more likely to develop high blood pressure. In prior studies, longer sleep duration is associated with lower BP, and SGA is associated with shorter sleep duration in childhood. We investigated whether sleep duration in early childhood modifies the association between SGA and higher childhood SBP in 1178 children recruited at birth and followed up to age 9 years. We ascertained birthweight and gestational age from medical records. We derived child sleep duration from maternal questionnaire interview. We calculated child SBP percentile according to U.S. reference data. We defined elevated SBP as SBP ≥75th percentile. In this sample, 154 (13.1%) children were born SGA. Children born SGA had higher SBP percentiles and higher risk of elevated SBP. Among children born SGA, those in the highest compared to the lowest tertile for sleep had a 12.28 lower (−22.00, −2.57) SBP percentile and 0.44 (0.25 to 0.79) times lower risk of developing elevated SBP. Our data are consistent with an interaction between SGA and sleep duration on childhood elevated SBP (Pinteraction = 0.0056). In conclusion, in this prospective birth cohort, longer sleep duration in early childhood may mitigate the blood pressure-raising effect of being born small.
Loss of Glis3 causes dysregulation of retrotransposon silencing and germ cell demise in fetal mouse testis
Authors: Ungewitter Erica K. , Rotgers Emmi , Kang Hong Soon , Lichti-Kaiser Kristin , Li Leping , Grimm Sara A. , Jetten Anton M. , Yao Humphrey H.-C. 
Published: June 2018

AbstractFetal germ cell development is regulated by an elaborate combination of cell-extrinsic and cell-intrinsic signals. Here we identify a novel role for the Krüppel-like transcription factor Gli-Similar 3 (Glis3) in male germ cell development in the mouse embryos. Glis3 is expressed in male germ cells during the brief window of time prior to initiation of piRNA-dependent retrotransposon surveillance. Disruption of Glis3 function led to a widespread reduction in retrotransposon silencing factors, aberrant retrotransposon expression and pronounced germ cell loss. Experimental induction of precocious Glis3 expression in vivo before its normal expression resulted in premature expression of several piRNA pathway members, suggesting that GLIS3 is necessary for the activation of the retrotransposon silencing programs. Our findings reveal an unexpected role for GLIS3 in the development of male germ cells and point to a central role for GLIS3 in the control of retrotransposon silencing in the fetal germline.
Phytate Decreases Formation of Advanced Glycation End-Products in Patients with Type II Diabetes: Randomized Crossover Trial
Authors: Sanchis Pilar , Rivera Rosmeri , Berga Francisco , Fortuny Regina , Adrover Miquel , Costa-Bauza Antonia , Grases Felix , Masmiquel Luis 
Published: June 2018

AbstractMyo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts and it has the ability to chelate metal cations. The binding of IP6 to transition metals suggests that it could be used for the treatment of metal-catalyzed protein glycation, which appears to trigger diabetes-related diseases. Our in vitro studies showed that IP6 reduced the formation of Fe3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a randomized cross-over trial to investigate the impact of the daily consumption IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n = 33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk factors, and urinary IP6 at baseline and at the end of the intervention period. Patients who consumed IP6 supplements for 3 months had lower levels of circulating AGEs and HbA1c than those who did not consume IP6. This is the first report to show that consumption of IP6 inhibits protein glycation in patients with T2DM. Considering that AGEs contribute to microvascular and macrovascular complications in T2DM, our data indicates that dietary supplementation with IP6 should be considered as a therapy to prevent the formation of AGEs and therefore, the development of diabetes-related diseases in patients with T2DM.
Evidence for neurogenesis in the medial cortex of the leopard gecko, Eublepharis macularius
Authors: McDonald Rebecca P. , Vickaryous Matthew K. 
Published: June 2018

AbstractAlthough lizards are often described as having robust neurogenic abilities, only a handful of the more than 6300 species have been explored. Here, we provide the first evidence of homeostatic neurogenesis in the leopard gecko (Eublepharis macularius). We focused our study on the medial cortex, homologue of the mammalian hippocampal formation. Using immunostaining, we identified proliferating pools of neural stem/progenitor cells within the sulcus septomedialis, the pseudostratified ventricular zone adjacent to the medial cortex. Consistent with their identification as radial glia, these cells expressed SOX2, glial fibrillary acidic protein, and Vimentin, and demonstrated a radial morphology. Using a 5-bromo-2′-deoxyuridine cell tracking strategy, we determined that neuroblast migration from the ventricular zone to the medial cortex takes ~30-days, and that newly generated neuronal cells survived for at least 140-days. We also found that cell proliferation within the medial cortex was not significantly altered following rupture of the tail spinal cord (as a result of the naturally evolved process of caudal autotomy). We conclude that the sulcus septomedialis of the leopard gecko demonstrates all the hallmarks of a neurogenic niche.
Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil
Authors: Omoto Shinya , Speranzini Valentina , Hashimoto Takashi , Noshi Takeshi , Yamaguchi Hiroto , Kawai Makoto , Kawaguchi Keiko , Uehara Takeki , Shishido Takao , Naito Akira , Cusack Stephen 
Published: June 2018

AbstractBaloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. In clinical trials, single doses of BXM profoundly decrease viral titers as well as alleviating influenza symptoms. Here, we characterize the impact on BXA susceptibility and replicative capacity of variant viruses detected in the post-treatment monitoring of the clinical studies. We find that the PA I38T substitution is a major pathway for reduced susceptibility to BXA, with 30- to 50-fold and 7-fold EC50 changes in A and B viruses, respectively. The viruses harboring the I38T substitution show severely impaired replicative fitness in cells, and correspondingly reduced endonuclease activity in vitro. Co-crystal structures of wild-type and I38T influenza A and B endonucleases bound to BXA show that the mutation reduces van der Waals contacts with the inhibitor. A reduced affinity to the I38T mutant is supported by the lower stability of the BXA-bound endonuclease. These mechanistic insights provide markers for future surveillance of treated populations.
Improved identification of concordant and discordant gene expression signatures using an updated rank-rank hypergeometric overlap approach
Authors: Cahill Kelly M. , Huo Zhiguang , Tseng George C. , Logan Ryan W. , Seney Marianne L. 
Published: June 2018

AbstractRecent advances in large-scale gene expression profiling necessitate concurrent development of biostatistical approaches to reveal meaningful biological relationships. Most analyses rely on significance thresholds for identifying differentially expressed genes. We use an approach to compare gene expression datasets using ‘threshold-free’ comparisons. Significance cut-offs to identify genes shared between datasets may be too stringent and may miss concordant patterns of gene expression with potential biological relevance. A threshold-free approach gaining popularity in several research areas, including neuroscience, is Rank–Rank Hypergeometric Overlap (RRHO). Genes are ranked by their p-value and effect size direction, and ranked lists are compared to identify significantly overlapping genes across a continuous significance gradient rather than at a single arbitrary cut-off. We have updated the previous RRHO analysis by accurately detecting overlap of genes changed in the same and opposite directions between two datasets. Here, we use simulated and real data to show the drawbacks of the previous algorithm as well as the utility of our new algorithm. For example, we show the power of detecting discordant transcriptional patterns in the postmortem brain of subjects with psychiatric disorders. The new R package, RRHO2, offers a new, more intuitive visualization of concordant and discordant gene overlap.
TNF inhibits catecholamine production from induced sympathetic neuron-like cells in rheumatoid arthritis and osteoarthritis in vitro
Authors: Herrmann Markus , Anders Sven , Straub Rainer H. , Jenei-Lanzl Zsuzsa 
Published: June 2018

AbstractSynovial adipose stem cells (sASC) can be differentiated into catecholamine-expressing sympathetic neuron-like cells to treat experimental arthritis. However, the pro-inflammatory tumor necrosis factor (TNF) is known to be toxic to catecholaminergic cells (see Parkinson disease), and this may prevent anti-inflammatory effects in inflamed tissue. We hypothesized that TNF exhibits inhibitory effects on human differentiated sympathetic tyrosine hydroxylase-positive (TH+) neuron-like cells. For the first time, iTH+ neuron-like sympathetic cells were generated from sACSs of rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Compared to untreated controls in both OA and RA, TNF-treated iTH+ cells demonstrated a weaker staining of catecholaminergic markers in cell cultures of RA/OA patients, and the amount of produced noradrenaline was markedly lower. These effects were reversed by etanercept. Exposure of iTH+ cells to synovial fluid of RA patients showed similar inhibitory effects. In mixed synovial cells, significant effects of TNF on catecholamine release were observed only in OA. This study shows that TNF inhibits iTH+ synovial cells leading to the decrease of secreted noradrenaline. This might be a reason why discovered newly appearing TH+ cells in the synovium are not able to develop their possible full anti-inflammatory role in arthritis.
DNA damage response induced by Etoposide promotes steroidogenesis via GADD45A in cultured adrenal cells
Authors: Tamamori-Adachi Mimi , Koga Akane , Susa Takao , Fujii Hiroko , Tsuchiya Masao , Okinaga Hiroko , Hisaki Harumi , Iizuka Masayoshi , Kitajima Shigetaka , Okazaki Tomoki 
Published: June 2018

AbstractGlucocorticoid production is regulated by adrenocorticotropic hormone (ACTH) via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway in the adrenal cortex, but the changes in steroidogenesis associated with aging are unknown. In this study, we show that cell-autonomous steroidogenesis is induced by non-ACTH- mediated genotoxic stress in human adrenocortical H295R cells. Low-dose etoposide (EP) was used to induce DNA damage as a genotoxic stress, leading to cellular senescence. We found that steroidogenesis was promoted in cells stained with γH2AX, a marker of DNA damaged cells. Among stress-associated and p53-inducible genes, the expression of GADD45A and steroidogenesis-related genes was significantly upregulated. Immunofluorescence analysis revealed that GADD45A accumulated in the nuclei. Metabolite assay using cultured media showed that EP-treated cells were induced to produce and secrete considerable amounts of glucocorticoid. Knockdown of GADD45A using small interfering RNA markedly inhibited the EP-induced upregulation of steroidogenesis-related gene expression, and glucocorticoid production. A p38MAPK inhibitor, but not a PKA inhibitor, suppressed EP-stimulated steroidogenesis. These results suggest that DNA damage itself promotes steroidogenesis via one or more unprecedented non-ACTH-mediated pathway. Specifically, GADD45A plays a crucial role in the steroidogenic processes triggered by EP-stimulated genotoxic stress. Our study sheds new light on an alternate mechanism of steroidogenesis in the adrenal cortex.
Transcriptome analysis of two contrasting rice cultivars during alkaline stress
Authors: Li Ning , Liu Hualong , Sun Jian , Zheng Hongliang , Wang Jingguo , Yang Luomiao , Zhao Hongwei , Zou Detang 
Published: June 2018

AbstractSoil alkalinity greatly affects plant growth and crop productivity. Although RNA-Seq analyses have been conducted to investigate genome-wide gene expression in response to alkaline stress in many plants, the expressions of alkali-responsive genes in rice have not been previously investigated. In this study, the transcriptomic data between an alkaline-tolerant (WD20342) and an alkaline-sensitive (Caidao) rice cultivar were compared under alkaline stress conditions. A total of 962 important alkali-responsive (IAR) genes from highly differentially expressed genes (DEGs) were identified, including 28 alkaline-resistant cultivar-related genes, 771 alkaline-sensitive cultivar-related genes and 163 cultivar-non-specific genes. Gene ontology (GO) analysis indicated the enrichment of IAR genes involved in various stimulus or stress responses. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the IAR genes were related primarily to plant hormone signal transduction and biosynthesis of secondary metabolites. Additionally, among these 962 IAR genes, 74 were transcription factors and 15 occurred with differential alternative splicing between the different samples after alkaline treatment. Our results provide a valuable resource on alkali-responsive genes and should benefit the improvement of alkaline stress tolerance in rice.
Elastic and dynamical structural properties of La and Mn-doped SrTiO3 studied by neutron scattering and their relation with thermal conductivities
Authors: Kajimoto Ryoichi , Nakamura Mitsutaka , Murai Naoki , Shamoto Shin-ichi , Honda Takashi , Ikeda Kazutaka , Otomo Toshiya , Hata Hiroto , Eto Takahiro , Noda Masaaki , Kuwahara Hideki , Okuda Tetsuji 
Published: June 2018

AbstractThe electron-doped SrTiO3 exhibits good thermoelectric properties, which makes this material a promising candidate of an n-type oxide thermoelectric device. Recent studies indicated that only a few percent co-doping of La and Mn in SrTiO3 substantially reduces the thermal conductivity, thereby greatly improving the thermoelectric figure of merit at room temperature. Our time-of-flight neutron scattering studies revealed that by doping both La and Mn into SrTiO3, the inelastic scattering spectrum shows a momentum-independent increase in the low-energy spectral weight approximately below 10 meV. The increase in the low-energy spectral weight exhibits a clear correlation with thermal conductivity. The correlation is attributed to dynamical and local structural fluctuations caused by the Jahn-Teller instability in Mn3+ ions coupled with the incipient ferroelectric nature of SrTiO3, as the origin of the low thermal conductivity.
First report on the application of near-infrared spectroscopy to predict the age of Aedes albopictus Skuse
Authors: Sikulu-Lord Maggy T. , Devine Gregor J. , Hugo Leon E. , Dowell Floyd E. 
Published: June 2018

AbstractTo date, no methodology has been described for predicting the age of Aedes albopictus Skuse mosquitoes, commonly known as Asian tiger mosquitoes. In this study, we report the potential of near-infrared spectroscopy (NIRS) technique for characterizing the age of female laboratory reared Ae. albopictus. Using leave-one-out cross-validation analysis on a training set, laboratory reared mosquitoes preserved in RNAlater for up to a month were assessed at 1, 3, 7, 9, 13, 16, 20 and 25 days post emergence. Mosquitoes (N = 322) were differentiated into two age classes (< or ≥ 7 days) with 93% accuracy, into three age classes (<7, 7–13 and >13 days old) with 76% accuracy, and on a continuous age scale to within ±3 days of their actual average age. Similarly, models predicted mosquitoes (N = 146) excluded from the training model with 94% and 71% accuracy to the two and the three age groups, respectively. We show for the first time that NIRS, with an improved spectrometer and fibre configuration, can be used to predict the age of laboratory reared female Ae. albopictus. Characterization of the age of Ae. albopictus populations is crucial for determining the efficacy of vector control interventions that target their survival.
Plasmonic refractive index sensing using strongly coupled metal nanoantennas: nonlocal limitations
Authors: Wang Hancong 
Published: June 2018

AbstractLocalized surface plasmon resonance based on coupled metallic nanoparticles has been extensively studied in the refractive index sensing and the detection of molecules. The amount of resonance peak-shift depends on the refractive index of surrounding medium and the geometry/symmetry of plasmonic oligomers. It has recently been found that as the feature size or the gap distance of plasmonic nanostructures approaches several nanometers, quantum effects can change the plasmon coupling in nanoparticles. However, most of the research on plasmonic sensing has been done based on classical local calculations even for the interparticle gap below ~3 nm, in which the nonlocal screening plays an important role. Here, we theoretically investigate the nonlocal effect on the evolution of various plasmon resonance modes in strongly coupled nanoparticle dimer and trimer antennas with the gap down to 1 nm. Then, the refractive index sensing in these nonlocal systems is evaluated and compared with the results in classical calculations. We find that in the nonlocal regime, both refractive index sensibility factor and figure of merit are actually smaller than their classical counterparts mainly due to the saturation of plasmon shifts. These results would be beneficial for the understanding of interaction between light and nonlocal plasmonic nanostructures and the development of plasmonic devices such as nanosensors and nanoantennas.
The Biological Object Notation (BON): a structured file format for biological data
Authors: Buchmann Jan P. , Fourment Mathieu , Holmes Edward C. 
Published: June 2018

AbstractThe large size and high complexity of biological data can represent a major methodological challenge for the analysis and exchange of data sets between computers and applications. There has also been a substantial increase in the amount of metadata associated with biological data sets, which is being increasingly incorporated into existing data formats. Despite the existence of structured formats based on XML, biological data sets are mainly formatted using unstructured file formats, and the incorporation of metadata results in increasingly complex parsing routines such that they become more error prone. To overcome these problems, we present the “biological object notation” (BON) format, a new way to exchange and parse nearly all biological data sets more efficiently and with less error than other currently available formats. Based on JavaScript Object Notation (JSON), BON simplifies parsing by clearly separating the biological data from its metadata and reduces complexity compared to XML based formats. The ability to selectively compress data up to 87% compared to other file formats and the reduced complexity results in improved transfer times and less error prone applications.
HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles
Authors: Lee Deokcheol , Taniguchi Noboru , Sato Katsuaki , Choijookhuu Narantsog , Hishikawa Yoshitaka , Kataoka Hiroaki , Morinaga Hidetaka , Lotz Martin , Chosa Etsuo 
Published: June 2018

AbstractAlthough various surgical procedures have been developed for chronic rotator cuff tear repair, the re-tear rate remains high with severe fat infiltration. However, little is known about the molecular regulation of this process. Mesenchymal stem cells (MSCs) in the intra-muscular space are origin of ectopic fat cells in skeletal muscle. We have previously shown that high-mobility group box 2 (HMGB2), which is a nuclear protein commonly associated with mesenchymal differentiation, is involved in the early articular cartilage degeneration. In this study, we addressed the role of HMGB2 in adipogenesis of MSCs and fat infiltration into skeletal muscles. HMGB2 was highly expressed in undifferentiated MSCs and co-localized with platelet-derived growth factor receptor α (PDGFRA) known as an MSC-specific marker, while their expressions were decreased during adipocytic differentiation. Under the deficiency of HMGB2, the expressions of adipogenesis-related molecules were reduced, and adipogenic differentiation is substantially impaired in MSCs. Moreover, HMGB2+ cells were generated in the muscle belly of rat supraspinatus muscles after rotator cuff transection, and some of these cells expressed PDGFRA in intra-muscular spaces. Thus, our findings suggest that the enhance expression of HMGB2 induces the adipogenesis of MSCs and the fat infiltration into skeletal muscles through the cascade of HMGB2-PDGFRA.