bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neddylation regulates excitatory synaptic transmission and plasticity
Authors: Brockmann Marisa M. , Döngi Michael , Einsfelder Ulf , Körber Nils , Refojo Damian , Stein Valentin 
Published: November 2019

AbstractPost-translational modifications, like phosphorylation, ubiquitylation, and sumoylation, have been shown to impact on synaptic neurotransmission by modifying pre- and postsynaptic proteins and therefore alter protein stability, localization, or protein-protein interactions. Previous studies showed that post-translational modifications are essential during the induction of synaptic plasticity, defined by a major reorganization of synaptic proteins. We demonstrated before that neddylation, a post-translational modification that covalently binds Nedd8 to lysine-residues, strongly affects neuronal maturation and spine stability. We now analysed the consequences of inhibiting neddylation on excitatory synaptic transmission and plasticity, which will help to narrow down possible targets, to make educated guesses, and test specific candidates. Here, we show that acute inhibition of neddylation impacts on synaptic neurotransmission before morphological changes occur. Our data indicate that pre- and postsynaptic proteins are neddylated since the inhibition of neddylation impacts on presynaptic release probability and postsynaptic receptor stabilization. In addition, blocking neddylation during the induction of long-term potentiation and long-term inhibition abolished both forms of synaptic plasticity. Therefore, this study shows the importance of identifying synaptic targets of the neddylation pathway to understand the regulation of synaptic transmission and plasticity.
Calorie restriction slows age-related microbiota changes in an Alzheimer’s disease model in female mice
Authors: Cox Laura M. , Schafer Marissa J. , Sohn Jiho , Vincentini Julia , Weiner Howard L. , Ginsberg Stephen D. , Blaser Martin J. 
Published: November 2019

AbstractAlzheimer’s disease (AD) affects an estimated 5.8 million Americans, and advanced age is the greatest risk factor. AD patients have altered intestinal microbiota. Accordingly, depleting intestinal microbiota in AD animal models reduces amyloid-beta (Aβ) plaque deposition. Age-related changes in the microbiota contribute to immunologic and physiologic decline. Translationally relevant dietary manipulations may be an effective approach to slow microbiota changes during aging. We previously showed that calorie restriction (CR) reduced brain Aβ deposition in the well-established Tg2576 mouse model of AD. Presently, we investigated whether CR alters the microbiome during aging. We found that female Tg2576 mice have more substantial age-related microbiome changes compared to wildtype (WT) mice, including an increase in Bacteroides, which were normalized by CR. Specific gut microbiota changes were linked to Aβ levels, with greater effects in females than in males. In the gut, Tg2576 female mice had an enhanced intestinal inflammatory transcriptional profile, which was reversed by CR. Furthermore, we demonstrate that Bacteroides colonization exacerbates Aβ deposition, which may be a mechanism whereby the gut impacts AD pathogenesis. These results suggest that long-term CR may alter the gut environment and prevent the expansion of microbes that contribute to age-related cognitive decline.
Construction of miRNA-target networks using microRNA profiles of CVB3-infected HeLa cells
Authors: Yao Hai Lan , Liu Mi , Wang Wen Jun , Wang Xin Ling , Song Juan , Song Qin Qin , Han Jun 
Published: November 2019

AbstractMicroRNAs (miRNAs) play an important role in regulating gene expression in multiple biological processes and diseases. Thus, to understand changes in miRNA during CVB3 infection, specific miRNA expression profiles were investigated at 3 h, 6 h, and 9 h postinfection in HeLa cells by small-RNA high-throughput sequencing. Biological implications of 68 differentially expressed miRNAs were analyzed through GO and KEGG pathways. Interaction networks between 34 known highly differentially expressed miRNAs and targets were constructed by mirDIP and Navigator. The predicted targets showed that FAM135A, IKZF2, PLAG1, ZNF148, PHC3, LCOR and DYRK1A, which are associated with cellular differentiation and transcriptional regulation, were recognized by 8 miRNAs or 9 miRNAs through interactional regulatory networks. Seven target genes were confirmed by RT-qPCR. The results showed that the expression of DYRK1A, FAM135A, PLAG1, ZNF148, and PHC3 were obviously inhibited at 3 h, 6 h, and 9 h postinfection. The expression of LCOR did not show a significant change, and the expression of IKZF2 increased gradually with prolonged infection time. Our findings improve the understanding of the pathogenic mechanism of CVB3 infection on cellular differentiation and development through miRNA regulation, which has implications for interventional approaches to CVB3-infection therapy. Our results also provide a new method for screening target genes of microRNA regulation in virus-infected cells.
Exotic species invasions undermine regional functional diversity of freshwater fish
Authors: Milardi Marco , Gavioli Anna , Soininen Janne , Castaldelli Giuseppe 
Published: November 2019

AbstractExotic species invasions often result in native biodiversity loss, i.e. a lower taxonomic diversity, but current knowledge on invasions effects underlined a potential increase of functional diversity. We thus explored the connections between functional diversity and exotic species invasions, while accounting for their environmental drivers, using a fine-resolution large dataset of Mediterranean stream fish communities. While functional diversity of native and exotic species responded similarly to most environmental constraints, we found significant differences in the effects of altitude and in the different ranking of constraints. These differences suggest that invasion dynamics could play a role in overriding some major environmental drivers. Our results also showed that a lower diversity of ecological traits in communities (about half of less disturbed communities) corresponded to a high invasion degree, and that the exotic component of communities had typically less diverse ecological traits than the native one, even when accounting for stream order and species richness. Overall, our results suggest that possible outcomes of severe exotic species invasions could include a reduced functional diversity of invaded communities, but analyzing data with finer ecological, temporal and spatial resolutions would be needed to pinpoint the causal relationship between invasions and functional diversity.
Fractionated head and neck irradiation impacts taste progenitors, differentiated taste cells, and Wnt/β-catenin signaling in adult mice
Authors: Gaillard Dany , Shechtman Lauren A. , Millar Sarah E. , Barlow Linda A. 
Published: November 2019

AbstractHead and neck cancer patients receiving conventional repeated, low dose radiotherapy (fractionated IR) suffer from taste dysfunction that can persist for months and often years after treatment. To understand the mechanisms underlying functional taste loss, we established a fractionated IR mouse model to characterize how taste buds are affected. Following fractionated IR, we found as in our previous study using single dose IR, taste progenitor proliferation was reduced and progenitor cell number declined, leading to interruption in the supply of new taste receptor cells to taste buds. However, in contrast to a single dose of IR, we did not encounter increased progenitor cell death in response to fractionated IR. Instead, fractionated IR induced death of cells within taste buds. Overall, taste buds were smaller and fewer following fractionated IR, and contained fewer differentiated cells. In response to fractionated IR, expression of Wnt pathway genes,Ctnnb1,Tcf7, Lef1andLgr5were reduced concomitantly with reduced progenitor proliferation. However, recovery of Wnt signaling post-IR lagged behind proliferative recovery. Overall, our data suggest carefully timed, local activation of Wnt/β-catenin signaling may mitigate radiation injury and/or speed recovery of taste cell renewal following fractionated IR.
The role and robustness of the Gini coefficient as an unbiased tool for the selection of Gini genes for normalising expression profiling data
Authors: Wright Muelas Marina , Mughal Farah , O’Hagan Steve , Day Philip J. , Kell Douglas B. 
Published: November 2019

AbstractWe recently introduced the Gini coefficient (GC) for assessing the expression variation of a particular gene in a dataset, as a means of selecting improved reference genes over the cohort (‘housekeeping genes’) typically used for normalisation in expression profiling studies. Those genes (transcripts) that we determined to be useable as reference genes differed greatly from previous suggestions based on hypothesis-driven approaches. A limitation of this initial study is that a single (albeit large) dataset was employed for both tissues and cell lines. We here extend this analysis to encompass seven other large datasets. Although their absolute values differ a little, the Gini values and median expression levels of the various genes are well correlated with each other between the various cell line datasets, implying that our original choice of the more ubiquitously expressed low-Gini-coefficient genes was indeed sound. In tissues, the Gini values and median expression levels of genes showed a greater variation, with the GC of genes changing with the number and types of tissues in the data sets. In all data sets, regardless of whether this was derived from tissues or cell lines, we also show that the GC is a robust measure of gene expression stability. Using the GC as a measure of expression stability we illustrate its utility to find tissue- and cell line-optimised housekeeping genes without any prior bias, that again include only a small number of previously reported housekeeping genes. We also independently confirmed this experimentally using RT-qPCR with 40 candidate GC genes in a panel of 10 cell lines. These were termed the Gini Genes. In many cases, the variation in the expression levels of classical reference genes is really quite huge (e.g. 44 fold for GAPDH in one data set), suggesting that the cure (of using them as normalising genes) may in some cases be worse than the disease (of not doing so). We recommend the present data-driven approach for the selection of reference genes by using the easy-to-calculate and robust GC.
Unravelling how low dominance in faces biases non-spatial attention
Authors: Roberts Ashton , Palermo Romina , Visser Troy A. W. 
Published: November 2019

AbstractAccording to the Dual Model of Social Hierarchy, one pathway for attaining social status is through dominance (coercion and intimidation). High dominance stimuli are known to more readily attract eye gaze and social attention. However, when there is a competition for non-spatial attentional resources, low dominance stimuli show an advantage. This low dominance bias was hypothesised to occur due to either counter-stereotypicality or attention competition. Here, these two hypotheses were examined across two experiments using modified versions of the attentional blink paradigm, used to measure non-spatial attention, and manipulations of facial dominance in both males and females. The results support the attention competition theory, suggesting that low dominance stimuli have a consistently strong ability to compete for attentional resources. Unexpectedly, high dominance stimuli fluctuate between having a strong and weak ability to compete for the same resources. The results challenge the current understanding of how humans interact with status.
The Screening and Evaluation of Fucus serratus and Fucus vesiculosus Extracts against Current Strains of MRSA Isolated from a Clinical Hospital Setting
Authors: Higgins Hoare Annabel , Tan Shiau Pin , McLoughlin Peter , Mulhare Patrick , Hughes Helen 
Published: November 2019

AbstractAntimicrobial resistant strains of infection are afflicting clinical settings, driving the search for novel antimicrobial compounds. Naturally sourced bioactives, for instance those from seaweeds, have the potential to ameliorate this issue. As such, solvent extracts from the edible Irish seaweeds Fucus serratus and Fucus vesiculosus were screened for antimicrobial activity against 28 clinically isolated strains of MRSA, including one GISA (glycopeptide intermediate S. aureus) and two mecC gene containing strains. The water extract of F. vesiculosus was the most promising extract went on to be tested for biofilm prevention and disruption activity. The disk diffusion method was used to investigate the inhibition of the bacterial pathogens tested while MIC, MBC and biofilm disruption and prevention analyses were performed spectroscopically and by plate counts, respectively. Solvent extracts were found to have a wide array of antimicrobial activity against the strains tested, with the water extract from Fucus vesiculosus being the most promising. This extract was also found to both prevent and disrupt MRSA biofilms indicating the potential extract as new antimicrobials, and raising the possibility of their possible use in therapeutics.
Glutamine/glutamate metabolism rewiring in reprogrammed human hepatocyte-like cells
Authors: Ballester Maria , Sentandreu Enrique , Luongo Giovanna , Santamaria Ramon , Bolonio Miguel , Alcoriza-Balaguer Maria Isabel , Palomino-Schätzlein Martina , Pineda-Lucena Antonio , Castell Jose , Lahoz Agustin , Bort Roque 
Published: November 2019

AbstractHuman dermal fibroblasts can be reprogrammed into hepatocyte-like (HEP-L) cells by the expression of a set of transcription factors. Yet, the metabolic rewiring suffered by reprogrammed fibroblasts remains largely unknown. Here we report, using stable isotope-resolved metabolic analysis in combination with metabolomic-lipidomic approaches that HEP-L cells mirrors glutamine/glutamate metabolism in primary cultured human hepatocytes that is very different from parental human fibroblasts. HEP-L cells diverge glutamine from multiple metabolic pathways into deamidation and glutamate secretion, just like periportal hepatocytes do. Exceptionally, glutamine contribution to lipogenic acetyl-CoA through reductive carboxylation is increased in HEP-L cells, recapitulating that of primary cultured human hepatocytes. These changes can be explained by transcriptomic rearrangements of genes involved in glutamine/glutamate metabolism. Although metabolic changes in HEP-L cells are in line with reprogramming towards the hepatocyte lineage, our conclusions are limited by the fact that HEP-L cells generated do not display a complete mature phenotype. Nevertheless, our findings are the first to characterize metabolic adaptation in HEP-L cells that could ultimately be targeted to improve fibroblasts direct reprogramming to HEP-L cells.
Enhancing the differentiation of specific genotypes in Mycobacterium tuberculosis population
Authors: Hadifar Shima , Kamakoli Mansour Kargarpour , Fateh Abolfazl , Siadat Seyed Davar , Vaziri Farzam 
Published: November 2019

AbstractToday, significant attention is directed towards the global lineages and sublineages of Mycobacterium tuberculosis (Mtb). NEW-1 (SIT 127) and CAS1-Delhi (SIT 26) strains are recognized as growing and circulating Mtb genotypes, especially in Asian countries. It is crucial to develop or enhance Mtb genotyping methods for a more accurate and simple differentiation of these families. We used 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing for genotyping 217 Mtb isolates. To select the optimal MIRU-VNTR loci, we calculated the Hunter-Gaston discriminatory index (HGDI), allelic diversity, and accumulation of percentage differences (APDs) between the strains among different groups of genotypes (NEW-1 and non-NEW-1; CAS1-Delhi and non-CAS). Finally, the minimum spanning tree was constructed for clustering analysis. In the NEW-1 population, loci with APD > 60% were found to have a high discriminatory power. VNTR loci with APD > 50% showed high discrimination power for the CAS population. Our findings suggest that APDs, which are valuable for the selection of VNTR loci sets, may improve the discriminatory power of MIRU-VNTR typing for identification of Mtb genotypes in specific regions.
A direct association between amber and dinosaur remains provides paleoecological insights
Authors: McKellar Ryan C. , Jones Emma , Engel Michael S. , Tappert Ralf , Wolfe Alexander P. , Muehlenbachs Karlis , Cockx Pierre , Koppelhus Eva B. , Currie Philip J. 
Published: November 2019

AbstractHadrosaurian dinosaurs were abundant in the Late Cretaceous of North America, but their habitats remain poorly understood. Cretaceous amber is also relatively abundant, yet it is seldom found in direct stratigraphic association with dinosaur remains. Here we describe an unusually large amber specimen attached to a Prosaurolophus jaw, which reveals details of the contemporaneous paleoforest and entomofauna. Fourier-transform Infrared spectroscopy and stable isotope composition (H and C) suggest the amber formed from resins exuded by cupressaceous conifers occupying a coastal plain. An aphid within the amber belongs to Cretamyzidae, a Cretaceous family suggested to bark-feed on conifers. Distinct tooth row impressions on the amber match the hadrosaur’s alveolar bone ridges, providing some insight into the taphonomic processes that brought these remains together.
Role of Kuroshio Current in fish resource variability off southwest Japan
Authors: Morioka Yushi , Varlamov Sergey , Miyazawa Yasumasa 
Published: November 2019

AbstractWestern boundary currents in the subtropics play a pivotal role in transporting warm water from the tropics that contribute to development of highly diverse marine ecosystem in the coastal regions. As one of the western boundary currents in the North Pacific, the Kuroshio Current (hereafter the Kuroshio) exerts great influences on biological resource variability off southwest Japan, but few studies have examined physical processes that attribute the coastal fish resource variability to the basin-scale Kuroshio variability. Using the high-quality fish catch data and high-resolution ocean reanalysis results, this study identifies statistical links of interannual fish resource variability off Sukumo Bay, Shikoku island of Japan, to subsurface ocean temperature variability in the Kuroshio. The subsurface ocean temperature variability off the south of Sukumo Bay exhibits vertically coherent structure with sea-surface height variability, which originates from the westward-propagating oceanic Rossby waves generated through surface wind anomalies in the Northwest Pacific. Although potential sources of the atmospheric variability remain unclarified, the remotely-induced oceanic Rossby waves contribute to fish resource variability off Sukumo Bay. These findings have potential applications to other coastal regions along the western boundary currents in the subtropics where the westward-propagating oceanic Rossby waves may contribute to coastal ocean temperature variability.
Stability under humidity, UV-light and bending of AZO films deposited by ALD on Kapton
Authors: Marques A. C. , Faria J. , Perdigão P. , Faustino B. M. M. , Ritasalo Riina , Costabello Katiuscia , da Silva R. C. , Ferreira I. 
Published: November 2019

AbstractAluminium doped zinc oxide (AZO) films were grown by Atomic Layer Deposition (ALD) on yellow Kapton and transparent Kapton (type CS) substrates for large area flexible transparent thermoelectric applications, which performance relies on the thermoelectric properties of the transparent AZO films. Therefore, their adhesion to Kapton, environmental and bending stability were accessed. Plasma treatment on Kapton substrates improved films adhesion, reduced cracks formation, and enhanced electrical resistance stability over time, of importance for long term thermoelectric applications in external environment. While exposure to UV light intensity caused the films electrical resistance to vary, and therefore their maximum power density outputs (0.3–0.4 mW/cm3) for a constant temperature difference (∼10 °C), humidity exposure and consecutive bending up to a curvature radius above the critical one (∼18 mm) not. Testing whether the films can benefit from encapsulation revealed that this can provide extra bending stability and prevent contacts deterioration in the long term.
Centromere 17 copy number gain reflects chromosomal instability in breast cancer
Authors: Lee Kyoungyul , Kim Hyun Jeong , Jang Min Hye , Lee Sejoon , Ahn Soomin , Park So Yeon 
Published: November 2019

AbstractChromosomal instability (CIN) is known to be associated with prognosis and treatment response in breast cancer. This study was conducted to determine whether copy number gain of centromere 17 (CEP17) reflects CIN, and to evaluate the prognostic and predictive value of CIN in breast cancer. CIN status was determined by summing copy number gains of four centromeric probes (CEP1, CEP8, CEP11, and CEP16) based on fluorescence in situ hybridization and CIN scores were calculated using next generation sequencing data. High CIN was associated with adverse clinicopatholgical parameters of breast cancer. Among them, positive HER2 status, high Ki-67 index and CEP17 copy number gain were found to be independent predictors of high CIN. High CIN was associated with poor clinical outcome of the patients in the whole group, as well as in luminal/HER2-negative and HER2-positive subtypes. CEP17 copy number was significantly higher in the high-CIN-score group than in the low-CIN-score group. A positive linear correlation between the mean CEP17 copy number and the CIN score was found. In conclusion, CEP17 copy number was confirmed as a useful predictor for CIN in breast cancer, and high CIN was revealed as an indicator of poor prognosis in breast cancer.
Non-SMC condensin I complex subunit H mediates mature chromosome condensation and DNA damage in pancreatic cancer cells
Authors: Kim Jae Hyeong , Youn Yuna , Kim Kyung-Tae , Jang Gyubeom , Hwang Jin-Hyeok 
Published: November 2019

AbstractNon-SMC condensin I complex subunit H (NCAPH) is a vital gene associated with chromosome stability and is required for proper chromosome condensation and segregation. However, the mechanisms through which NCAPH affects pancreatic cancer (PC) and its molecular function remain unclear. In this study, we examined the role of NCAPH in PC cells. Our results showed that NCAPH was overexpressed in clinical PC specimens (GEPIA) and cell lines. In addition, in NCAPH-knockdown cells, colony formation and proliferation were inhibited, and the cell cycle was arrested at the S and G2/M phases owing to failure of mature chromosome condensation (MCC) in poorly condensed chromosomes. Increased cell death in NCAPH-knockdown cells was found to help initiate apoptosis through the activation of caspase-3 and PARP cleavage. Furthermore, NCAPH-knockdown cells showed an increase in chromosomal aberrations and DNA damage via activation of the DNA damage response (Chk1/Chk2) signaling pathways. These data demonstrated that NCAPH played an important role in cell cycle progression and DNA damage by maintaining chromosomal stability through progression of MCC from poorly condensed chromosomes. Ultimately, NCAPH knockdown induced apoptotic cell death, which was partially mediated by caspase-dependent pathways. These findings highlight the potential role of NCAPH as a therapeutic target for PC.