bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control
Authors: Pawlyn C , Bright M D , Buros A F , Stein C K , Walters Z , Aronson L I , Mirabella F , Jones J R , Kaiser M F , Walker B A , Jackson G H , Clarke P A , Bergsagel P L , Workman P , Chesi M , Morgan G J , Davies F E 
Published: March 2017

AbstractMyeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly defined high-risk patients who continue to do badly. Novel therapeutic approaches are, therefore, required. A growing number of epigenetic inhibitors are now available including EZH2 inhibitors that are in early-stage clinical trials for treatment of haematological and other cancers with EZH2 mutations or in which overexpression has been correlated with poor outcomes. For the first time, we have identified and validated a robust and independent deleterious effect of high EZH2 expression on outcomes in myeloma patients. Using two chemically distinct small-molecule inhibitors, we demonstrate a reduction in myeloma cell proliferation with EZH2 inhibition, which leads to cell cycle arrest followed by apoptosis. This is mediated via upregulation of cyclin-dependent kinase inhibitors associated with removal of the inhibitory H3K27me3 mark at their gene loci. Our results suggest that EZH2 inhibition may be a potential therapeutic strategy for the treatment of myeloma and should be investigated in clinical studies.
Hidden diversity revealed by genome-resolved metagenomics of iron-oxidizing microbial mats from Lō’ihi Seamount, Hawai’i
Authors: Fullerton Heather , Hager Kevin W , McAllister Sean M , Moyer Craig L 
Published: March 2017

AbstractThe Zetaproteobacteria are ubiquitous in marine environments, yet this class of Proteobacteria is only represented by a few closely-related cultured isolates. In high-iron environments, such as diffuse hydrothermal vents, the Zetaproteobacteria are important members of the community driving its structure. Biogeography of Zetaproteobacteria has shown two ubiquitous operational taxonomic units (OTUs), yet much is unknown about their genomic diversity. Genome-resolved metagenomics allows for the specific binning of microbial genomes based on genomic signatures present in composite metagenome assemblies. This resulted in the recovery of 93 genome bins, of which 34 were classified as Zetaproteobacteria. Form II ribulose 1,5-bisphosphate carboxylase genes were recovered from nearly all the Zetaproteobacteria genome bins. In addition, the Zetaproteobacteria genome bins contain genes for uptake and utilization of bioavailable nitrogen, detoxification of arsenic, and a terminal electron acceptor adapted for low oxygen concentration. Our results also support the hypothesis of a Cyc2-like protein as the site for iron oxidation, now detected across a majority of the Zetaproteobacteria genome bins. Whole genome comparisons showed a high genomic diversity across the Zetaproteobacteria OTUs and genome bins that were previously unidentified by SSU rRNA gene analysis. A single lineage of cosmopolitan Zetaproteobacteria (zOTU 2) was found to be monophyletic, based on cluster analysis of average nucleotide identity and average amino acid identity comparisons. From these data, we can begin to pinpoint genomic adaptations of the more ecologically ubiquitous Zetaproteobacteria, and further understand their environmental constraints and metabolic potential.
Dispersion/dilution enhances phytoplankton blooms in low-nutrient waters
Authors: Lehahn Yoav , Koren Ilan , Sharoni Shlomit , d’Ovidio Francesco , Vardi Assaf , Boss Emmanuel 
Published: March 2017

AbstractSpatial characteristics of phytoplankton blooms often reflect the horizontal transport properties of the oceanic turbulent flow in which they are embedded. Classically, bloom response to horizontal stirring is regarded in terms of generation of patchiness following large-scale bloom initiation. Here, using satellite observations from the North Pacific Subtropical Gyre and a simple ecosystem model, we show that the opposite scenario of turbulence dispersing and diluting fine-scale (∼1–100 km) nutrient-enriched water patches has the critical effect of regulating the dynamics of nutrients–phytoplankton–zooplankton ecosystems and enhancing accumulation of photosynthetic biomass in low-nutrient oceanic environments. A key factor in determining ecological and biogeochemical consequences of turbulent stirring is the horizontal dilution rate, which depends on the effective eddy diffusivity and surface area of the enriched patches. Implementation of the notion of horizontal dilution rate explains quantitatively plankton response to turbulence and improves our ability to represent ecological and biogeochemical processes in oligotrophic oceans.
Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation
Authors: Vanheusden Marjan , Broux Bieke , Welten Suzanne P. M. , Peeters Liesbet M. , Panagioti Eleni , Van Wijmeersch Bart , Somers Veerle , Stinissen Piet , Arens Ramon , Hellings Niels 
Published: March 2017

AbstractCytomegalovirus (CMV) is a latent virus which causes chronic activation of the immune system. Here, we demonstrate that cytotoxic and pro-inflammatory CD4+CD28null T cells are only present in CMV seropositive donors and that CMV-specific Immunoglobulin (Ig) G titers correlate with the percentage of these cells. In vitro stimulation of peripheral blood mononuclear cells with CMVpp65 peptide resulted in the expansion of pre-existing CD4+CD28null T cells. In vivo, we observed de novo formation, as well as expansion of CD4+CD28null T cells in two different chronic inflammation models, namely the murine CMV (MCMV) model and the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis (MS). In EAE, the percentage of peripheral CD4+CD28null T cells correlated with disease severity. Pre-exposure to MCMV further aggravated EAE symptoms, which was paralleled by peripheral expansion of CD4+CD28null T cells, increased splenocyte MOG reactivity and higher levels of spinal cord demyelination. Cytotoxic CD4+ T cells were identified in demyelinated spinal cord regions, suggesting that peripherally expanded CD4+CD28null T cells migrate towards the central nervous system to inflict damage. Taken together, we demonstrate that CMV drives the expansion of CD4+CD28null T cells, thereby boosting the activation of disease-specific CD4+ T cells and aggravating autoimmune mediated inflammation and demyelination.
Differential activation of endocrine-immune networks by arthritis challenge: Insights from colony-specific responses
Authors: Bodnar Tamara S. , Taves Matthew D. , Lavigne Katie M. , Woodward Todd S. , Soma Kiran K. , Weinberg Joanne 
Published: March 2017

AbstractRheumatoid arthritis (RA) is a chronic inflammatory condition with variable clinical presentation and disease progression. Importantly, animal models of RA are widely used to examine disease pathophysiology/treatments. Here, we exploited known vendor colony-based differences in endocrine/immune responses to gain insight into inflammatory modulators in arthritis, utilizing the adjuvant-induced arthritis (AA) model. Our previous study found that Sprague-Dawley (SD) rats from Harlan develop more severe AA, have lower corticosteroid binding globulin, and have different patterns of cytokine activation in the hind paw, compared to SD rats from Charles River. Here, we extend these findings, demonstrating that Harlan rats show reduced hypothalamic cytokine responses to AA, compared to Charles River rats, and identify colony-based differences in cytokine profiles in hippocampus and spleen. To go beyond individual measures, probing for networks of variables underlying differential responses, we combined datasets from this and the previous study and performed constrained principal component analysis (CPCA). CPCA revealed that with AA, Charles River rats show activation of chemokine and central cytokine networks, whereas Harlan rats activate peripheral immune/hypothalamic-pituitary-adrenal networks. These data suggest differential underlying disease mechanism(s), highlighting the power of evaluating multiple disease biomarkers, with potential implications for understanding differential disease profiles in individuals with RA.
Carbon and Nitrogen Speciation in N-poor C-O-H-N Fluids at 6.3 GPa and 1100–1400 °C
Authors: Sokol Alexander G. , Tomilenko Anatoly A. , Bul’bak Taras A. , Palyanova Galina A. , Sokol Ivan A. , Palyanov Yury N. 
Published: March 2017

AbstractDeep carbon and nitrogen cycles played a critical role in the evolution of the Earth. Here we report on successful studying of speciation in C-O-H-N systems with low nitrogen contents at 6.3 GPa and 1100 to 1400 °C. At fO2 near Fe–FeO (IW) equilibrium, the synthesised fluids contain more than thirty species. Among them, CH4, C2H6, C3H8 and C4H10 are main carbon species. All carbon species, except for C1-C4 alkanes and alcohols, occur in negligible amounts in the fluids generated in systems with low H2O, but С15-С18 alkanes are slightly higher and oxygenated hydrocarbons are more diverse at higher temperatures and H2O concentrations. At a higher oxygen fugacity of +2.5 Δlog fO2 (IW), the fluids almost lack methane and contain about 1 rel.% C2-C4 alkanes, as well as fractions of percent of C15–18 alkanes and notable contents of alcohols and carboxylic acids. Methanimine (CH3N) is inferred to be the main nitrogen species in N-poor reduced fluids. Therefore, the behaviour of CH3N may control the nitrogen cycle in N-poor peridotitic mantle. Oxidation of fluids strongly reduces the concentration of CH4 and bulk carbon. However, higher alkanes, alcohols, and carboxylic acids can resist oxidation and should remain stable in mantle hydrous magmas.
Single Molecule Translation Imaging Visualizes the Dynamics of Local β-Actin Synthesis in Retinal Axons
Authors: Ströhl Florian , Lin Julie Qiaojin , Laine Romain F. , Wong Hovy Ho-Wai , Urbančič Vasja , Cagnetta Roberta , Holt Christine E. , Kaminski Clemens F. 
Published: March 2017

AbstractLocal mRNA translation occurs in growing axons enabling precise control of the proteome in response to signals. To measure quantitatively the spatiotemporal dynamics of protein synthesis in growth cones, we further developed a technique for single molecule translation imaging (SMTI). We report that Netrin-1 triggers a burst of β-actin synthesis at multiple non-repetitive sites, particularly in the periphery. The response is remarkably rapid starting within 20 seconds of cue application.
Eastern Mediterranean Mobility in the Bronze and Early Iron Ages: Inferences from Ancient DNA of Pigs and Cattle
Authors: Meiri Meirav , Stockhammer Philipp W. , Marom Nimrod , Bar-Oz Guy , Sapir-Hen Lidar , Morgenstern Peggy , Macheridis Stella , Rosen Baruch , Huchon Dorothée , Maran Joseph , Finkelstein Israel 
Published: March 2017

AbstractThe Late Bronze of the Eastern Mediterranean (1550–1150 BCE) was a period of strong commercial relations and great prosperity, which ended in collapse and migration of groups to the Levant. Here we aim at studying the translocation of cattle and pigs during this period. We sequenced the first ancient mitochondrial and Y chromosome DNA of cattle from Greece and Israel and compared the results with morphometric analysis of the metacarpal in cattle. We also increased previous ancient pig DNA datasets from Israel and extracted the first mitochondrial DNA for samples from Greece. We found that pigs underwent a complex translocation history, with links between Anatolia with southeastern Europe in the Bronze Age, and movement from southeastern Europe to the Levant in the Iron I (ca. 1150–950 BCE). Our genetic data did not indicate movement of cattle between the Aegean region and the southern Levant. We detected the earliest evidence for crossbreeding between taurine and zebu cattle in the Iron IIA (ca. 900 BCE). In light of archaeological and historical evidence on Egyptian imperial domination in the region in the Late Bronze Age, we suggest that Egypt attempted to expand dry farming in the region in a period of severe droughts.
THz Electric Field-Induced Second Harmonic Generation in Inorganic Ferroelectric
Authors: Grishunin Kirill A. , Ilyin Nikita A. , Sherstyuk Natalia E. , Mishina Elena D. , Kimel Alexey , Mukhortov Vladimir M. , Ovchinnikov Andrey V. , Chefonov Oleg V. , Agranat Mikhail B. 
Published: March 2017

AbstractSecond Harmonic Generation induced by the electric field of a strong nearly single-cycle terahertz pulse with the peak amplitude of 300 kV/cm is studied in a classical inorganic ferroelectric thin film of (Ba0.8Sr0.2)TiO3. The dependences of the SHG intensity on the polarization of the incoming light is revealed and interpreted in terms of electric polarization induced in the plane of the film. As the THz pulse pumps the medium in the range of phononic excitations, the induced polarization is explained as a dynamical change of the ferrolectric order parameter. It is estimated that under action of the THz pulse the ferroelectric order parameter acquires an in-plane component up to 6% of the net polarization.
Multiple begomoviruses found associated with cotton leaf curl disease in Pakistan in early 1990 are back in cultivated cotton
Authors: Zubair Muhammad , Zaidi Syed Shan-e-Ali , Shakir Sara , Farooq Muhammad , Amin Imran , Scheffler Jodi A. , Scheffler Brian E. , Mansoor Shahid 
Published: March 2017

AbstractThe first epidemic of cotton leaf curl disease (CLCuD) in early 1990’s in the Indian subcontinent was associated with several distinct begomoviruses along with a disease-specific betasatellite. Resistant cotton varieties were introduced in late 1990’s but soon resistance was broken and was associated with a single recombinant begomovirus named Burewala strain of Cotton leaf curl Kokhran virus that lacks a full complement of a gene encoding a transcription activator protein (TrAP). In order to understand the ongoing changes in CLCuD complex in Pakistan, CLCuD affected plants from cotton fields at Vehari were collected. Illumina sequencing was used to assess the diversity of CLCuD complex. At least three distinct begomoviruses characterized from the first epidemic; Cotton leaf curl Multan virus, Cotton leaf curl Kokhran virus and Cotton leaf curl Alabad virus, several distinct species of alphasatellites and cotton leaf curl Multan betasatellite were found associated with CLCuD. These viruses were also cloned and sequenced through Sanger sequencing to confirm the identity of the begomoviruses and that all clones possessed a full complement of the TrAP gene. A new strain of betasatellite was identified here and named CLCuMuBVeh. The implications of these findings in efforts to control CLCuD are discussed.
The underlying process of early ecological and genetic differentiation in a facultative mutualistic Sinorhizobium meliloti population
Authors: Toro Nicolás , Villadas Pablo J. , Molina-Sánchez María Dolores , Navarro-Gómez Pilar , Vinardell José M. , Cuesta-Berrio Lidia , Rodríguez-Carvajal Miguel A. 
Published: March 2017

AbstractThe question of how genotypic and ecological units arise and spread in natural microbial populations remains controversial in the field of evolutionary biology. Here, we investigated the early stages of ecological and genetic differentiation in a highly clonal sympatric Sinorhizobium meliloti population. Whole-genome sequencing revealed that a large DNA region of the symbiotic plasmid pSymB was replaced in some isolates with a similar synteny block carrying densely clustered SNPs and displaying gene acquisition and loss. Two different versions of this genomic island of differentiation (GID) generated by multiple genetic exchanges over time appear to have arisen recently, through recombination in a particular clade within this population. In addition, these isolates display resistance to phages from the same geographic region, probably due to the modification of surface components by the acquired genes. Our results suggest that an underlying process of early ecological and genetic differentiation in S. meliloti is primarily triggered by acquisition of genes that confer resistance to soil phages within particular large genomic DNA regions prone to recombination.
Cancer-associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression
Authors: Zeraati Mahdi , Moye Aaron L. , Wong Jason W. H. , Perera Dilmi , Cowley Mark J. , Christ Daniel U. , Bryan Tracy M. , Dinger Marcel E. 
Published: March 2017

AbstractCancer is a multifactorial disease driven by a combination of genetic and environmental factors. Many cancer driver mutations have been characterised in protein-coding regions of the genome. However, mutations in noncoding regions associated with cancer have been less investigated. G-quadruplex (G4) nucleic acids are four-stranded secondary structures formed in guanine-rich sequences and prevalent in the regulatory regions. In this study, we used published whole cancer genome sequence data to find mutations in cancer patients that overlap potential RNA G4-forming sequences in 5′ UTRs. Using RNAfold, we assessed the effect of these mutations on the thermodynamic stability of predicted RNA G4s in the context of full-length 5′ UTRs. Of the 217 identified mutations, we found that 33 are predicted to destabilise and 21 predicted to stabilise potential RNA G4s. We experimentally validated the effect of destabilising mutations in the 5′ UTRs of BCL2 and CXCL14 and one stabilising mutation in the 5′ UTR of TAOK2. These mutations resulted in an increase or a decrease in translation of these mRNAs, respectively. These findings suggest that mutations that modulate the G4 stability in the noncoding regions could act as cancer driver mutations, which present an opportunity for early cancer diagnosis using individual sequencing information.
The fractal organization of ultradian rhythms in avian behavior
Authors: Guzmán Diego A. , Flesia Ana G. , Aon Miguel A. , Pellegrini Stefania , Marin Raúl H. , Kembro Jackelyn M. 
Published: March 2017

AbstractLiving systems exhibit non-randomly organized biochemical, physiological, and behavioral processes that follow distinctive patterns. In particular, animal behavior displays both fractal dynamics and periodic rhythms yet the relationship between these two dynamic regimens remain unexplored. Herein we studied locomotor time series of visually isolated Japanese quails sampled every 0.5 s during 6.5 days (>106data points). These high-resolution, week-long, time series enabled simultaneous evaluation of ultradian rhythms as well as fractal organization according to six different analytical methods that included Power Spectrum, Enright, Empirical Mode Decomposition, Wavelet, and Detrended Fluctuation analyses. Time series analyses showed that all birds exhibit circadian rhythms. Although interindividual differences were detected, animals presented ultradian behavioral rhythms of 12, 8, 6, 4.8, 4 h and/or lower and, irrespective of visual isolation, synchronization between these ultradian rhythms was observed. Moreover, all birds presented similar overall fractal dynamics (for scales ∼30 s to >4.4 h). This is the first demonstration that avian behavior presents fractal organization that predominates at shorter time scales and coexists with synchronized ultradian rhythms. This chronobiological pattern is advantageous for keeping the organism’s endogenous rhythms in phase with internal and environmental periodicities, notably the feeding, light-dark and sleep-wake cycles.
Modelling the three-dimensional structure of the right-terminal domain of pospiviroids
Authors: Steger Gerhard 
Published: March 2017

AbstractViroids, the smallest know plant pathogens, consist solely of a circular, single-stranded, non-coding RNA. Thus for all of their biological functions, like replication, processing, and transport, they have to present sequence or structural features to exploit host proteins. Viroid binding protein 1 (Virp1) is indispensable for replication of pospiviroids, the largest genus of viroids, in a host plant as well as in protoplasts. Virp1 is known to bind at two sites in the terminal right (TR) domain of pospiviroids; each site consists of a purine- (R-) and a pyrimidine- (Y-)rich motif that are partially base-paired to each other. Here we model the important structural features of the domain and show that it contains an internal loop of two Y · Y cis Watson-Crick/Watson-Crick (cWW) pairs, an asymmetric internal loop including a cWW and a trans Watson/Hoogsteen pair, and a thermodynamically quite stable hairpin loop with several stacking interactions. These features are discussed in connection to the known biological functions of the TR domain.
Preovulatory suppression of mouse oocyte cell volume-regulatory mechanisms is via signalling that is distinct from meiotic arrest
Authors: Richard Samantha , Baltz Jay M. 
Published: March 2017

AbstractGLYT1-mediated glycine transport is the main cell volume-homeostatic mechanism in mouse eggs and early preimplantation embryos. It is unique to these developmental stages and key to their healthy development. GLYT1 first becomes activated in oocytes only after ovulation is triggered, when meiotic arrest of the oocyte is released, but how this occurs was unknown. Here we show that GLYT1 activity is suppressed in oocytes in the preovulatory antral follicle and that its suppression is mediated by a mechanism distinct from the gap junction-dependent Natriuretic Peptide Precursor C (NPPC) pathway that controls meiotic arrest. GLYT1 remained suppressed in isolated antral follicles but not isolated cumulus-oocyte complexes (COCs) or isolated oocytes. Moreover, activating the NPPC signalling pathway could not prevent GLYT1 activation in oocytes within COCs despite maintaining meiotic arrest. Furthermore, blocking gap junctions in isolated follicles failed to induce GLYT1 activity in enclosed oocytes for an extended period after meiosis had resumed. Finally, isolated mural granulosa cells from preovulatory antral follicles were sufficient to suppress GLYT1 in oocytes within co-cultured COCs. Together, these results suggest that suppression of GLYT1 activity before ovulation is mediated by a novel signalling pathway likely originating from preovulatory mural granulosa cells.
Salvia fruticosa Induces Vasorelaxation In Rat Isolated Thoracic Aorta: Role of the PI3K/Akt/eNOS/NO/cGMP Signaling Pathway
Authors: Anwar M. Akhtar , Samaha Ali A. , Ballan Samar , Saleh Alaaeldin I. , Iratni Rabah , Eid Ali H. 
Published: March 2017

AbstractSalvia fruticosa (SF) Mill. is traditionally used for its antihypertensive actions. However, little is known about its pharmacologic and molecular mechanisms of action. Here we determined the effects of an ethanolic extract of SF leaves on rings of isolated thoracic aorta from Sprague-Dawley rats. Our results show that SF extract increased nitric oxide production and relaxed endothelium-intact rings in a dose-dependent (0.3 µg/ml–1 mg/ml) manner, and the maximum arterial relaxation (Rmax) was significantly reduced with endothelium denudation. Pretreatment of endothelium-intact rings with L-NAME (a non-selective inhibitor of nitric oxide synthase, 100 µM), or ODQ (an inhibitor of soluble guanylyl cyclase, 10 µM) significantly diminished SF-mediated vasorelaxation. Furthermore, SF induced Akt phosphorylation as well as increased cGMP levels in rings treated with increasing doses of SF. Prior exposure to PI3K inhibitors, wortmannin (0.1 µM) or LY294002 (10 µM), decreased cGMP accumulation and attenuated the SF-induced vasorelaxation by approximately 50% (Rmax). SF-evoked relaxation was not affected by indomethacin, verapamil, glibenclamide, tetraethylammonium, pyrilamine or atropine. Taken together, our results indicate that SF induces endothelium-dependent vasorelaxation through the PI3K/Akt/eNOS/NO/sGC/cGMP signaling pathway. Our data illustrate the health-orientated benefits of consuming SF which may act as an antihypertensive agent to reduce the burden of cardiovascular complications.