bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenome-wide association studies identify DNA methylation associated with kidney function
Authors: Chu Audrey Y. , Tin Adrienne , Schlosser Pascal , Ko Yi-An , Qiu Chengxiang , Yao Chen , Joehanes Roby , Grams Morgan E. , Liang Liming , Gluck Caroline A. , Liu Chunyu , Coresh Josef , Hwang Shih-Jen , Levy Daniel , Boerwinkle Eric , Pankow James S. , Yang Qiong , Fornage Myriam , Fox Caroline S. , Susztak Katalin , Köttgen Anna 
Published: October 2017

AbstractChronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs atPTPN6/PHB2,ANKRD11, andTNRC18map to active enhancers in kidney cortex. AtPTPN6/PHB2cg19942083, methylation in kidney cortex associates with lower renalPTPN6expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.
Autoinhibitory sterol sulfates mediate programmed cell death in a bloom-forming marine diatom
Authors: Gallo Carmela , d’Ippolito Giuliana , Nuzzo Genoveffa , Sardo Angela , Fontana Angelo 
Published: October 2017

AbstractCell mortality is a key mechanism that shapes phytoplankton blooms and species dynamics in aquatic environments. Here we show that sterol sulfates (StS) are regulatory molecules of a cell death program in Skeletonema marinoi, a marine diatom-blooming species in temperate coastal waters. The molecules trigger an oxidative burst and production of nitric oxide in a dose-dependent manner. The intracellular level of StS increases with cell ageing and ultimately leads to a mechanism of apoptosis-like death. Disrupting StS biosynthesis by inhibition of the sulfonation step significantly delays the onset of this fatal process and maintains steady growth in algal cells for several days. The autoinhibitory activity of StS demonstrates the functional significance of small metabolites in diatoms. The StS pathway provides another view on cell regulation during bloom dynamics in marine habitats and opens new opportunities for the biochemical control of mass-cultivation of microalgae.
High-frequency recombination between members of an LTR retrotransposon family during transposition bursts
Authors: Sanchez Diego H. , Gaubert Hervé , Drost Hajk-Georg , Zabet Nicolae Radu , Paszkowski Jerzy 
Published: October 2017

AbstractRetrotransposons containing long terminal repeats (LTRs) form a substantial fraction of eukaryotic genomes. The timing of past transposition can be estimated by quantifying the accumulation of mutations in initially identical LTRs. This way, retrotransposons are divided into young, potentially mobile elements, and old that moved thousands or even millions of years ago. Both types are found within a single retrotransposon family and it is assumed that the old members will remain immobile and degenerate further. Here, we provide evidence in Arabidopsis that old members enter into replication/transposition cycles through high rates of intra-family recombination. The recombination occurs pairwise, resembling the formation of recombinant retroviruses. Thus, each transposition burst generates a novel progeny population of chromosomally integrated LTR retrotransposons consisting of pairwise recombination products produced in a process comparable the sexual exchange of genetic information. Our observations provide an explanation for the reported high rates of sequence diversification in retrotransposons.
Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917
Authors: Pérez-Berezo Teresa , Pujo Julien , Martin Patricia , Le Faouder Pauline , Galano Jean-Marie , Guy Alexandre , Knauf Claude , Tabet Jean Claude , Tronnet Sophie , Barreau Frederick , Heuillet Maud , Dietrich Gilles , Bertrand-Michel Justine , Durand Thierry , Oswald Eric , Cenac Nicolas 
Published: October 2017

AbstractAdministration of the probiotic Escherichia coli strain Nissle 1917 (EcN) decreases visceral pain associated with irritable bowel syndrome. Mutation of clbA, a gene involved in the biosynthesis of secondary metabolites, including colibactin, was previously shown to abrogate EcN probiotic activity. Here, we show that EcN, but not an isogenic clbA mutant, produces an analgesic lipopeptide. We characterize lipoamino acids and lipopeptides produced by EcN but not by the mutant by online liquid chromatography mass spectrometry. One of these lipopeptides, C12AsnGABAOH, is able to cross the epithelial barrier and to inhibit calcium flux induced by nociceptor activation in sensory neurons via the GABAB receptor. C12AsnGABAOH inhibits visceral hypersensitivity induced by nociceptor activation in mice. Thus, EcN produces a visceral analgesic, which could be the basis for the development of new visceral pain therapies.
Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass
Authors: Borensztein Maud , Okamoto Ikuhiro , Syx Laurène , Guilbaud Guillaume , Picard Christel , Ancelin Katia , Galupa Rafael , Diabangouaya Patricia , Servant Nicolas , Barillot Emmanuel , Surani Azim , Saitou Mitinori , Chen Chong-Jian , Anastassiadis Konstantinos , Heard Edith 
Published: October 2017

AbstractX-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27. We further show that in UTX H3K27 histone demethylase mutant embryos, these genes are even more slowly reactivated, suggesting that these genes carry an epigenetic memory that may be actively lost. On the other hand, expression of rapidly reactivated genes may be driven by transcription factors. Thus, some X-linked genes have minimal epigenetic memory in the inner cell mass, whereas others may require active erasure of chromatin marks.
piRNAs and Aubergine cooperate with Wispy poly(A) polymerase to stabilize mRNAs in the germ plasm
Authors: Dufourt Jérémy , Bontonou Gwénaëlle , Chartier Aymeric , Jahan Camille , Meunier Anne-Cécile , Pierson Stéphanie , Harrison Paul F. , Papin Catherine , Beilharz Traude H. , Simonelig Martine 
Published: October 2017

AbstractPiwi-interacting RNAs (piRNAs) and PIWI proteins play a crucial role in germ cells by repressing transposable elements and regulating gene expression. In Drosophila, maternal piRNAs are loaded into the embryo mostly bound to the PIWI protein Aubergine (Aub). Aub targets maternal mRNAs through incomplete base-pairing with piRNAs and can induce their destabilization in the somatic part of the embryo. Paradoxically, these Aub-dependent unstable mRNAs encode germ cell determinants that are selectively stabilized in the germ plasm. Here we show that piRNAs and Aub actively protect germ cell mRNAs in the germ plasm. Aub directly interacts with the germline-specific poly(A) polymerase Wispy, thus leading to mRNA polyadenylation and stabilization in the germ plasm. These results reveal a role for piRNAs in mRNA stabilization and identify Aub as an interactor of Wispy for mRNA polyadenylation. They further highlight the role of Aub and piRNAs in embryonic patterning through two opposite functions.
Stochastic palmitoylation of accessible cysteines in membrane proteins revealed by native mass spectrometry
Authors: Rodenburg Remco N. P. , Snijder Joost , van de Waterbeemd Michiel , Schouten Arie , Granneman Joke , Heck Albert J. R. , Gros Piet 
Published: October 2017

AbstractPalmitoylation affects membrane partitioning, trafficking and activities of membrane proteins. However, how specificity of palmitoylation and multiple palmitoylations in membrane proteins are determined is not well understood. Here, we profile palmitoylation states of three human claudins, human CD20 and cysteine-engineered prokaryotic KcsA and bacteriorhodopsin by native mass spectrometry. Cysteine scanning of claudin-3, KcsA, and bacteriorhodopsin shows that palmitoylation is independent of a sequence motif. Palmitoylations are observed for cysteines exposed on the protein surface and situated up to 8 Å into the inner leaflet of the membrane. Palmitoylation on multiple sites in claudin-3 and CD20 occurs stochastically, giving rise to a distribution of palmitoylated membrane-protein isoforms. Non-native sites in claudin-3 indicate that membrane-protein function imposed evolutionary restraints on native palmitoylation sites. These results suggest a generic, stochastic membrane-protein palmitoylation process that is determined by the accessibility of palmitoyl-acyl transferases to cysteines on membrane-embedded proteins, and not by a preferred substrate-sequence motif.
Hall voltage drives pulsing counter-currents of the sliding charge density wave and of quantized normal carriers at self-filled Landau levels
Authors: Orlov Andrey P. , Sinchenko Aleksander A. , Monceau Pierre , Brazovskii Serguei , Latyshev Yuri I. 
Published: October 2017

AbstractRemnant pockets of carriers left over after formation of a charge density wave (CDW) were brought, by virtue of transverse electric and magnetic fields, to a current-carrying state at quantized Landau Levels. The generated Hall voltage polarizes and puts to sliding the flexible CDW background. The screening from the CDW allows for a so strong redistribution of normal electrons density under the action of the Lorentz force alone, that an integer filling of the lowest Landau level might be reached at one edge at the expense of the full depletion at another edge of the Hall bar. With the Hall field exceeding the sliding threshold, the regime of exactly compensated collective and normal counter-currents develops in the open-circuit direction across the bar. The annihilation of the two currents proceeds via a regular sequence of phase slips which are the space-time vortices of the CDW phase around the enforced amplitude nodes. The resulting spontaneous generation of coherent high (~GHz) frequency signals was detected by observations of multiple Shapiro steps. This picture results from studies of micron-sized Hall bars in crystals of NbSe3 prepared by means of focused ion beams. The interpretation is confirmed and illustrated by a numerical solution of the derived equations. The depinning pulse propagates from edges to the bulk and the sliding sets in, accompanied by the generation of periodic phase slips near the Hall bar edge where the CDW phase is advanced in steps of 2π at expense of the CDW amplitude passing through zero.
Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus
Authors: Ma Jingjiao , Lee Jinhwa , Liu Haixia , Mena Ignacio , Davis A. Sally , Sunwoo Sun Young , Lang Yuekun , Duff Michael , Morozov Igor , Li Yuhao , Yang Jianmei , García-Sastre Adolfo , Richt Juergen A. , Ma Wenjun 
Published: October 2017

AbstractSince December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5Nx viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5Nx viruses and can be used by mass application to protect the poultry industry.
In human non-REM sleep, more slow-wave activity leads to less blood flow in the prefrontal cortex
Authors: Tüshaus Laura , Omlin Ximena , Tuura Ruth O’Gorman , Federspiel Andrea , Luechinger Roger , Staempfli Philipp , Koenig Thomas , Achermann Peter 
Published: October 2017

AbstractCerebral blood flow (CBF) is related to integrated neuronal activity of the brain whereas EEG provides a more direct measurement of transient neuronal activity. Therefore, we addressed what happens in the brain during sleep, combining CBF and EEG recordings. The dynamic relationship of CBF with slow-wave activity (SWA; EEG sleep intensity marker) corroborated vigilance state specific (i.e., wake, non-rapid eye movement (NREM) sleep stages N1-N3, wake after sleep) differences of CBF e.g. in the posterior cingulate, basal ganglia, and thalamus, indicating their role in sleep-wake regulation and/or sleep processes. These newly observed dynamic correlations of CBF with SWA – namely a temporal relationship during continuous NREM sleep in individuals – additionally implicate an impact of sleep intensity on the brain’s metabolism. Furthermore, we propose that some of the aforementioned brain areas that also have been shown to be affected in disorders of consciousness might therefore contribute to the emergence of consciousness.
In vitro selections of mammaglobin A and mammaglobin B aptamers for the recognition of circulating breast tumor cells
Authors: Hassan Eman M. , Willmore William G. , McKay Bruce C. , DeRosa Maria C. 
Published: October 2017

AbstractMammaglobin B (MGB2) and mammaglobin A (MGB1) are proteins expressed in metastatic breast cancers. The early detection of circulating tumor cells (CTCs) in breast cancer patients is crucial to decrease mortality rate. Herein, novel aptamers were successfully selected and characterized against MGB2 and MGB1 proteins using a hybrid SELEX approach. The potential use of the selected aptamers in breast CTC detection was studied using spiked breast cancer cells in whole blood lysate. The results obtained from this study showed that the selected aptamers (MAMB1 and MAMA2) bind to their target breast cancer cell lines with high affinity (low nanomolar Kd values) and specificity. They also bind to their free recombinant target proteins and show minimal non-specific binding to normal and other cancer cell lines. Additionally, they were able to distinguish a low number of breast cancer cells spiked in whole blood lysate containing normal blood cells. The results obtained in this study indicate the great potential for the use of aptamers to detect MGB1 and MGB2 protein biomarkers, expressed on the surface of breast CTCs.
Enhanced Arctic Amplification Began at the Mid-Brunhes Event ~400,000 years ago
Authors: Cronin T. M. , Dwyer G. S. , Caverly E. K. , Farmer J. , DeNinno L. H. , Rodriguez-Lazaro J. , Gemery L. 
Published: October 2017

AbstractArctic Ocean temperatures influence ecosystems, sea ice, species diversity, biogeochemical cycling, seafloor methane stability, deep-sea circulation, and CO2 cycling. Today’s Arctic Ocean and surrounding regions are undergoing climatic changes often attributed to “Arctic amplification” – that is, amplified warming in Arctic regions due to sea-ice loss and other processes, relative to global mean temperature. However, the long-term evolution of Arctic amplification is poorly constrained due to lack of continuous sediment proxy records of Arctic Ocean temperature, sea ice cover and circulation. Here we present reconstructions of Arctic Ocean intermediate depth water (AIW) temperatures and sea-ice cover spanning the last ~ 1.5 million years (Ma) of orbitally-paced glacial/interglacial cycles (GIC). Using Mg/Ca paleothermometry of the ostracode Krithe and sea-ice planktic and benthic indicator species, we suggest that the Mid-Brunhes Event (MBE), a major climate transition ~ 400–350 ka, involved fundamental changes in AIW temperature and sea-ice variability. Enhanced Arctic amplification at the MBE suggests a major climate threshold was reached at ~ 400 ka involving Atlantic Meridional Overturning Circulation (AMOC), inflowing warm Atlantic Layer water, ice sheet, sea-ice and ice-shelf feedbacks, and sensitivity to higher post-MBE interglacial CO2 concentrations.
A comparison of the main outcomes from BP-BES and DP-DES at five years of follow-up: A systematic review and meta-analysis
Authors: Lu Pan , Lu Shuai , Li Yuanyuan , Deng Mengmeng , Wang Zhaohui , Mao Xiaobo 
Published: October 2017

AbstractBiodegradable polymer biolimus-eluting stents (BP-BES) are third-generation drug-eluting stents (DES) composed of biodegradable polymers that may improve prognosis after percutaneous coronary intervention (PCI). After five years of follow-up, BP-BES showed conflicting results compared to durable polymer drug-eluting stents (DP-DES). We performed a meta-analysis of the outcomes of studies on BP-BES and DP-DES after percutaneous coronary intervention (PCI) at five years of follow-up. Eligible studies were retrieved from PubMed, Embase and the Cochrane Library and reported the results of all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and stent thrombosis (ST) at five years of follow-up. Five studies of a total of 4687 patients were included in the meta-analysis. At five years of follow-up, BP-BES was associated with lower rates of major adverse cardiac events (MACE) (OR = 0.83, 95%CI = [0.71, 0.97]), TLR (OR = 0.77, 95%CI = [0.62, 0.96]) and ST (OR = 0.60, 95%CI = [0.43 to 0.84]), whereas no significant differences in mortality, MI, or TVR rates were detected. Our results demonstrated that at five years of follow-up, BP-BES can significantly reduce the risk of MACE, TLR and ST, which indicate that safety and efficacy were increased after PCI.
Utf1 contributes to intergenerational epigenetic inheritance of pluripotency
Authors: Bao Qiuye , Morshedi Amir , Wang Fulu , Bhargy Sharma , Pervushin Konstantin , Yu Wei-Ping , Dröge Peter 
Published: October 2017

AbstractUndifferentiated embryonic cell transcription factor 1 (Utf1) is expressed in pluripotent embryonic stem cells (ESCs) and primordial germ cells (PGCs). Utf1 expression is directly controlled by pluripotency factors Oct4 and Sox2, which form a ternary complex with the Utf1 enhancer. The Utf1 protein plays a role in chromatin organization and epigenetic control of bivalent gene expression in ESCs in vitro, where it promotes effective cell differentiation during exit from pluripotency. The function of Utf1 in PGCs in vivo, however, is not known. Here, we report that proper development of Utf1 null embryos almost entirely depends on the presence of functional Utf1 alleles in the parental germline. This indicates that Utf1’s proposed epigenetic role in ESC pluripotency in vitro may be linked to intergenerational epigenetic inheritance in vivo. One component - or at least facilitator - of the relevant epigenetic mark appears to be Utf1 itself, since Utf1-driven tomato reporter and Utf1 are detected in mature germ cells. We also provide initial evidence for a reduced adult testis size in Utf1 null mice. Our findings thus point at unexpected functional links between the core ESC pluripotency factor network and epigenetic inheritance of pluripotency.
Trapping and manipulation of nanoparticles using multifocal optical vortex metalens
Authors: Ma Yanbao , Rui Guanghao , Gu Bing , Cui Yiping 
Published: October 2017

AbstractOptical trapping and manipulation have emerged as a powerful tool in the biological and physical sciences. In this work, we present a miniature optical tweezers device based on multifocal optical vortex metalens (MOVM). The MOVM is capable of generating multiple focal fields with specific orbital angular momentum at arbitrary position. The optical force of the vortex field exerted on both high-refractive-index particle and low-refractive-index particle are analyzed. The simulation results show that the two kinds of dielectric particles can be trapped simultaneously. Besides, it is also feasible to manipulate plasmonic nanoparticles even under the resonant condition, which is realized by constructing a 4Pi focusing system with metalenses. Moreover, the metalens can be made into an array format that is suitable for trapping and manipulating various nanoparticles with diverse motion behaviors. The work illustrates the potential of such optical tweezers for further development in lab-on-a-chip devices, and may open up new avenues for optical manipulation and their applications in extensive scientific fields.
Transforming Growth Factor-beta Regulation of Ephrin Type-A Receptor 4 Signaling in Breast Cancer Cellular Migration
Authors: Hachim Ibrahim Y. , Villatoro Manuel , Canaff Lucie , Hachim Mahmood Y. , Boudreault Julien , Haiub Halema , Ali Suhad , Lebrun Jean-Jacques 
Published: October 2017

AbstractBreast cancer consists of a range of tumor subtypes with different clinical characteristics, disease prognosis, and treatment-response. Luminal breast cancer has the best prognosis while basal-like breast cancer (BLBC) represents the worst subtype. Transforming growth factor-beta (TGFβ) plays a prominent role in stimulating the migration and invasion of malignant breast cancer cells contributing to tumor progression. In this study, we identified the Ephrin type-A receptor 4 (EPHA4) as a novel target of TGFβ in breast cancer. Moreover, we show that TGFβ induction of EPHA4 gene expression is specific to basal-like tumors and is required for TGFβ-mediated cell migration. We further addressed the mechanism and found EPHA4 to be required for TGFβ-mediated cell migration in breast cancer through TGFβ-induced short term and long term activation of RhoGTPases. Finally, our data revealed a strong association between high EPHA4 expression and advanced tumor stage, aggressive BLBC molecular subtype and poor prognosis. Importantly, we found significant co-expression of EPHA4 and the TGFβ receptor type-2 (TGFβR2) in breast cancer subtypes associated with increased tumor relapse and drug resistance. Together, this study highlight the important role of the TGFβ/EPHA4 signaling axis in mediating tumor aggressiveness and poor patient survival in human breast cancer.