bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective deletion of the soluble Colony-Stimulating Factor 1 isoform in vivo prevents estrogen-deficiency bone loss in mice
Authors: Yao Gang-Qing , Troiano Nancy , Simpson Christine A , Insogna Karl L 
Published: November 2017

AbstractNeutralizing CSF1in vivocompletely prevents ovariectomy (OVX)-induced bone loss in mice. There are two isoforms of CSF1, soluble (sCSF1), and membrane-bound (mCSF1), but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout (K/O) and wild type (Wt) female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected (sCSF1 K/O). Isoform-specific reverse transcription PCR confirmed the absence of transcripts for sCSF1 in bone tissue isolated from these animals and no circulating CSF1 was detected by ELISA. Surprisingly, there were no significant differences in bone mineral density (BMD) between sCSF1 K/O mice and Wt controls as assessed by dual-energy X-ray absorptiometry and micro-CT. However, one month after OVX, femoral, spinal and total BMD had declined by 11.2%, 8.9%, and 8.7% respectively in OVX-Wt animals as compared to Sham-OVX. In contrast OVX sCSF1 K/O mice showed changes of +0.1%, −2.4%, and +2.3% at the same 3 sites compared to Sham-OVX sCSF1 K/O mice. These data indicate important non-redundant functions for the two isoforms of CSF1 and suggest that sCSF1, but not mCSF1, plays a key role in estrogen-deficiency bone loss.
Two approaches reveal a new paradigm of ‘switchable or genetics-influenced allele-specific DNA methylation’ with potential in human disease
Authors: Martos Suzanne N , Li Teng , Ramos Ramon Bossardi , Lou Dan , Dai Hongzheng , Xu Jin-Chong , Gao Ganglong , Gao Yang , Wang Qinglu , An Cheng , Zhang Xueli , Jia Yankai , Dawson Valina L , Dawson Ted M , Ji Hongkai , Wang Zhibin 
Published: November 2017

AbstractImprinted genes are vulnerable to environmental influences during early embryonic development, thereby contributing to the onset of disease in adulthood. Monoallelic methylation at several germline imprints has been reported as DNMT1-dependent. However, which of these two epigenetic attributes, DNMT1-dependence or allelic methylation, renders imprinted genes susceptible to environmental stressors has not been determined. Herein, we developed a new approach, referred to as NORED, to identify 2468 DNMT1-dependent DNA methylation patterns in the mouse genome. We further developed an algorithm based on a genetic variation-independent approach (referred to as MethylMosaic) to detect 2487 regions with bimodal methylation patterns. Two approaches identified 207 regions, including known imprinted germline allele-specific methylation patterns (ASMs), that were both NORED and MethylMosaic regions. Examination of methylation in four independent mouse embryonic stem cell lines shows that two regions identified by both NORED and MethylMosaic (Hcn2 and Park7) did not display parent-of-origin-dependent allelic methylation. In these four F1 hybrid cell lines, genetic variation in Cast allele at Hcn2 locus introduces a transcription factor binding site for MTF-1 that may predispose Cast allelic hypomethylation in a reciprocal cross with either C57 or 129 strains. In contrast, each allele of Hcn2 ASM in J1 inbred cell line and Park7 ASM in four F1 hybrid cell lines seems to exhibit similar propensity to be either hypo- or hypermethylated, suggesting a ‘random, switchable’ ASM. Together with published results, our data on ASMs prompted us to propose a hypothesis of regional ‘autosomal chromosome inactivation (ACI)’ that may control a subset of autosomal genes. Therefore, our results open a new avenue to understand monoallelic methylation and provide a rich resource of candidate genes to examine in environmental and nutritional exposure models.
Metabolic shift at the class level sheds light on adaptation of methanogens to oxidative environments
Authors: Lyu Zhe , Lu Yahai 
Published: November 2017

Abstract
Methanogens have long been considered strictly anaerobic and oxygen-sensitive microorganisms, but their ability to survive oxygen stress has also been documented. Indeed, methanogens have been found in oxidative environments, and antioxidant genes have been detected in their genomes. How methanogens adapt to oxidative environments, however, remain poorly understood. Here, we systematically predicted and annotated antioxidant features from representative genomes across six well-established methanogen orders. Based on functional gene content involved in production of reactive oxygen species, Hierarchical Clustering analyses grouped methanogens into two distinct clusters, corresponding to the Class I and II methanogens, respectively. Comparative genomics suggested a systematic shift in metabolisms across the two classes, resulting in an enrichment of antioxidant features in the Class II. Moreover, meta-analysis of 16 S rRNA gene sequences obtained from EnvDB indicated that members of Class II were more frequently recovered from microaerophilic and even oxic environments than the Class I members. Phylogenomic analysis suggested that the Class I and II methanogens might have evolved before and around the Great Oxygenation Event, respectively. The enrichment of antioxidant features in the Class II methanogens may have played a key role in the adaption of this group to oxidative environments today and historically.
Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling
Authors: Pal Bhupinder , Chen Yunshun , Vaillant François , Jamieson Paul , Gordon Lavinia , Rios Anne C. , Wilcox Stephen , Fu Naiyang , Liu Kevin He , Jackling Felicity C. , Davis Melissa J. , Lindeman Geoffrey J. , Smyth Gordon K. , Visvader Jane E. 
Published: November 2017

AbstractThe mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells.
Structural and spatial chromatin features at developmental gene loci in human pluripotent stem cells
Authors: Ikeda Hiroki , Sone Masamitsu , Yamanaka Shinya , Yamamoto Takuya 
Published: November 2017

AbstractHigher-order chromatin organization controls transcriptional programs that govern cell properties and functions. In order for pluripotent stem cells (PSCs) to appropriately respond to differentiation signals, developmental gene loci should be structurally and spatially regulated to be readily available for immediate transcription, even though these genes are hardly expressed in PSCs. Here, we show that both chromatin interaction profiles and nuclear positions at developmental gene loci differ between human somatic cells and hPSCs, and that changes in the chromatin interactions are closely related to the nuclear repositioning. Moreover, we also demonstrate that developmental gene loci, which have bivalent histone modifications, tend to colocalize in PSCs. Furthermore, this colocalization requires PRC1, PRC2, and TrxG complexes, which are essential regulatory factors for the maintenance of transcriptionally poised developmental genes. Our results indicate that higher-order chromatin regulation may be an integral part of the differentiation capacity that defines pluripotency.
Host-genotype dependent gut microbiota drives zooplankton tolerance to toxic cyanobacteria
Authors: Macke Emilie , Callens Martijn , De Meester Luc , Decaestecker Ellen 
Published: November 2017

AbstractThe gut microbiota impacts many aspects of its host’s biology, and is increasingly considered as a key factor mediating performance of host individuals in continuously changing environments. Here we use gut microbiota transplants to show that both host genotype and gut microbiota mediate tolerance to toxic cyanobacteria in the freshwater crustacean Daphnia magna. Interclonal variation in tolerance to cyanobacteria disappears when Daphnia are made germ-free and inoculated with an identical microbial inoculum. Instead, variation in tolerance among recipient Daphnia mirrors that of the microbiota donors. Metagenetic analyses point to host genotype and external microbial source as important determinants of gut microbiota assembly, and reveal strong differences in gut microbiota composition between tolerant and susceptible genotypes. Together, these results show that both environmentally and host genotype-induced variations in gut microbiota structure mediate Daphnia tolerance to toxic cyanobacteria, pointing to the gut microbiota as a driver of adaptation and acclimatization to cyanobacterial harmful algal blooms in zooplankton.
Mapping the sugar dependency for rational generation of a DNA-RNA hybrid-guided Cas9 endonuclease
Authors: Rueda Fernando Orden , Bista Michal , Newton Matthew D. , Goeppert Anne U. , Cuomo M. Emanuela , Gordon Euan , Kröner Felix , Read Jon A. , Wrigley Jonathan D. , Rueda David , Taylor Benjamin J. M. 
Published: November 2017

AbstractThe CRISPR–Cas9 RNA-guided endonuclease system allows precise and efficient modification of complex genomes and is continuously developed to enhance specificity, alter targeting and add new functional moieties. However, one area yet to be explored is the base chemistry of the associated RNA molecules. Here we show the design and optimisation of hybrid DNA–RNA CRISPR and tracr molecules based on structure-guided approaches. Through careful mapping of the ribose requirements of Cas9, we develop hybrid versions possessing minimal RNA residues, which are sufficient to direct specific nuclease activity in vitro and in vivo with reduced off-target activity. We identify critical regions within these molecules that require ribose nucleotides and show a direct correlation between binding affinity/stability and cellular activity. This is the first demonstration of a non-RNA-guided Cas9 endonuclease and first step towards eliminating the ribose dependency of Cas9 to develop a XNA-programmable endonuclease.
Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling
Authors: Sassi Yassine , Avramopoulos Petros , Ramanujam Deepak , Grüter Laurenz , Werfel Stanislas , Giosele Simon , Brunner Andreas-David , Esfandyari Dena , Papadopoulou Aikaterini S. , De Strooper Bart , Hübner Norbert , Kumarswamy Regalla , Thum Thomas , Yin Xiaoke , Mayr Manuel , Laggerbauer Bernhard , Engelhardt Stefan 
Published: November 2017

AbstractChronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function. Targeted deletion of miR-29 in cardiac myocytes in vivo also prevents cardiac hypertrophy and fibrosis, indicating that the function of miR-29 in cardiac myocytes dominates over that in non-myocyte cell types. Mechanistically, we found cardiac myocyte miR-29 to de-repress Wnt signaling by directly targeting four pathway factors. Our data suggests that, cell- or tissue-specific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis.
Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair
Authors: Boye Theresa Louise , Maeda Kenji , Pezeshkian Weria , Sønder Stine Lauritzen , Haeger Swantje Christin , Gerke Volker , Simonsen Adam Cohen , Nylandsted Jesper 
Published: November 2017

AbstractEfficient cell membrane repair mechanisms are essential for maintaining membrane integrity and thus for cell life. Here we show that the Ca2+- and phospholipid-binding proteins annexin A4 and A6 are involved in plasma membrane repair and needed for rapid closure of micron-size holes. We demonstrate that annexin A4 binds to artificial membranes and generates curvature force initiated from free edges, whereas annexin A6 induces constriction force. In cells, plasma membrane injury and Ca2+ influx recruit annexin A4 to the vicinity of membrane wound edges where its homo-trimerization leads to membrane curvature near the edges. We propose that curvature force is utilized together with annexin A6-mediated constriction force to pull the wound edges together for eventual fusion. We show that annexin A4 can counteract various plasma membrane disruptions including holes of several micrometers indicating that induction of curvature force around wound edges is an early key event in cell membrane repair.
Selective excitation of spin-polarized alkali atoms in different ground-state hyperfine levels
Authors: Ding Zhichao , Yuan Jie , Fu Yangying , Luo Hui , Long Xingwu 
Published: November 2017

AbstractA technique to selectively excite spin-polarized alkali atoms in one of the two ground-state hyperfine levels is demonstrated, which can separately create the transverse spin component of spin-polarized alkali atoms in either ground-state hyperfine level. The principle of this technique is analyzed, and the experimental results are found to be in good agreement with the theoretical predictions, thereby demonstrating the feasibility of this technique. This technique can be used to accurately measure spin relaxation and polarization of alkali atoms in either ground-state hyperfine level. An example of its applications to measure the transverse relaxation time is presented.
Characterization and Separation Performance of a Novel Polyethersulfone Membrane Blended with Acacia Gum
Authors: Manawi Yehia , Kochkodan Viktor , Mahmoudi Ebrahim , Johnson Daniel J. , Mohammad Abdul Wahab , Atieh Muataz Ali 
Published: November 2017

AbstractNovel polyethersulfone (PES) membranes blended with 0.1–3.0 wt. % of Acacia gum (AG) as a pore-former and antifouling agent were fabricated using phase inversion technique. The effect of AG on the pore-size, porosity, surface morphology, surface charge, hydrophilicity, and mechanical properties of PES/AG membranes was studied by scanning electron microscopy (SEM), Raman spectroscopy, contact angle and zeta potential measurements. The antifouling -properties of PES/AG membranes were evaluated using Escherichia coli bacteria and bovine serum albumine (BSA). The use of AG as an additive to PES membranes was found to increase the surface charge, hydrophilicity (by 20%), porosity (by 77%) and permeate flux (by about 130%). Moreover, PES/AG membranes demonstrated higher antifouling and tensile stress (by 31%) when compared to pure PES membranes. It was shown that the prepared PES/AG membranes efficiently removed lead ions from aqueous solutions. Both the sieving mechanism of the membrane and chelation of lead with AG macromolecules incorporated in the membrane matrix contributed to lead removal. The obtained results indicated that AG can be used as a novel pore-former, hydrophilizing and antifouling agent, as well as an enhancer to the mechanical and rejection properties of the PES membranes.
Azole sensitivity in Leptosphaeria pathogens of oilseed rape: the role of lanosterol 14α-demethylase
Authors: Sewell Thomas R. , Hawkins Nichola J. , Stotz Henrik U. , Huang YongJu , Kelly Steven L. , Kelly Diane E. , Fraaije Bart , Fitt Bruce D. L. 
Published: November 2017

AbstractLanosterol 14-α demethylase is a key enzyme intermediating the biosynthesis of ergosterol in fungi, and the target of azole fungicides. Studies have suggested thatLeptosphaeria maculansandL. biglobosa, the causal agents of phoma stem canker on oilseed rape, differ in their sensitivity to some azoles, which could be driving pathogen frequency change in crops. Here we used CYP51 protein modelling and heterologous expression to determine whether there are interspecific differences at the target-site level. Moreover, we provide an example of intrinsic sensitivity differences exhibited by bothLeptosphaeriaspp.in vitroandin planta. Comparison of homologous protein models identified highly conserved residues, particularly at the azole binding site, and heterologous expression of LmCYP51B and LbCYP51B, with fungicide sensitivity testing of the transformants, suggests that both proteins are similarly sensitive to azole fungicides flusilazole, prothioconazole-desthio and tebuconazole. Fungicide sensitivity testing on isolates shows that they sometimes have a minor difference in sensitivityin vitroandin planta. These results suggest that azole fungicides remain a useful component of integrated phoma stem canker control in the UK due to their effectiveness on bothLeptosphaeriaspp. Other factors, such as varietal resistance or climate, may be driving observed frequency changes between species.
Using a Single VCSEL Source Employing OFDM Downstream Signal and Remodulated OOK Upstream Signal for Bi-directional Visible Light Communications
Authors: Yeh Chien-Hung , Wei Liang-Yu , Chow Chi-Wai 
Published: November 2017

AbstractIn this work, we propose and demonstrate for the first time up to our knowledge, using a 682 nm visible vertical-cavity surface-emitting laser (VCSEL) applied in a bi-directional wavelength remodulated VLC system with a free space transmission distance of 3 m. To achieve a high VLC downstream traffic, spectral efficient orthogonal-frequency-division-multiplexing quadrature-amplitude-modulation (OFDM-QAM) with bit and power loading algorithms are applied on the VCSEL in the central office (CO). The OFDM downstream wavelength is remodulated by an acousto-optic modulator (AOM) with OOK modulation to produce the upstream traffic in the client side. Hence, only a single VCSEL laser is needed for the proposed bi-directional VLC system, achieving 10.6 Gbit/s OFDM downstream and 2 Mbit/s remodulated OOK upstream simultaneously. For the proposed system, as a single laser source with wavelength remodulation is used, the laser wavelength and temperature managements at the client side are not needed; and the whole system could be cost effective and energy efficient.
Calcium binding and voltage gating in Cx46 hemichannels
Authors: Pinto Bernardo I. , Pupo Amaury , García Isaac E. , Mena-Ulecia Karel , Martínez Agustín D. , Latorre Ramón , Gonzalez Carlos 
Published: November 2017

AbstractThe opening of connexin (Cx) hemichannels in the membrane is tightly regulated by calcium (Ca2+) and membrane voltage. Electrophysiological and atomic force microscopy experiments indicate that Ca2+ stabilizes the hemichannel closed state. However, structural data show that Ca2+ binding induces an electrostatic seal preventing ion transport without significant structural rearrangements. In agreement with the closed-state stabilization hypothesis, we found that the apparent Ca2+ sensitivity is increased as the voltage is made more negative. Moreover, the voltage and Ca2+ dependence of the channel kinetics indicate that the voltage sensor movement and Ca2+ binding are allosterically coupled. An allosteric kinetic model in which the Ca2+ decreases the energy necessary to deactivate the voltage sensor reproduces the effects of Ca2+ and voltage in Cx46 hemichannels. In agreement with the model and suggesting a conformational change that narrows the pore, Ca2+ inhibits the water flux through Cx hemichannels. We conclude that Ca2+ and voltage act allosterically to stabilize the closed conformation of Cx46 hemichannels.
Field sampling marine plankton for biodiscovery
Authors: Ingebrigtsen Richard Andre , Hansen Espen , Andersen Jeanette Hammer , Eilertsen Hans Christian 
Published: November 2017

AbstractMicroalgae and plankton can be a rich source of bioactivity. However, induction of secondary metabolite production in lab conditions can be difficult. One simple way of bypassing this issue is to collect biomass in the field and screen for bioactivity. Therefore, bulk net samples from three areas along the coast of northern Norway and Spitsbergen were collected, extracted and fractionated. Biomass samples from a strain of a mass-cultivated diatom Porosira glacialis were used as a reference for comparison to field samples. Screening for bioactivity was performed with 13 assays within four therapeutic areas: antibacterial, anticancer, antidiabetes and antioxidation. We analysed the metabolic profiles of the samples using high resolution - mass spectroscopy (HR-MS). Principal component analysis showed a marked difference in metabolite profiles between the field samples and the photobioreactor culture; furthermore, the number of active fractions and extent of bioactivity was different in the field compared to the photobioreactor samples. We found varying levels of bioactivity in all samples, indicating that complex marine field samples could be used to investigate bioactivities from otherwise inaccessible sources. Furthermore, we hypothesize that metabolic pathways that would otherwise been silent under controlled growth in monocultures, might have been activated in the field samples.
High-injection effects in near-field thermophotovoltaic devices
Authors: Blandre Etienne , Chapuis Pierre-Olivier , Vaillon Rodolphe 
Published: November 2017

AbstractIn near-field thermophotovoltaics, a substantial enhancement of the electrical power output is expected as a result of the larger photogeneration of electron-hole pairs due to the tunneling of evanescent modes from the thermal radiator to the photovoltaic cell. The common low-injection approximation, which considers that the local carrier density due to photogeneration is moderate in comparison to that due to doping, needs therefore to be assessed. By solving the full drift-diffusion equations, the existence of high-injection effects is studied in the case of a GaSb p-on-n junction cell and a radiator supporting surface polaritons. Depending on doping densities and surface recombination velocity, results reveal that high-injection phenomena can already take place in the far field and become very significant in the near field. Impacts of high injection on maximum electrical power, short-circuit current, open-circuit voltage, recombination rates, and variations of the difference between quasi-Fermi levels are analyzed in detail. By showing that an optimum acceptor doping density can be estimated, this work suggests that a detailed and accurate modeling of the electrical transport is also key for the design of near-field thermophotovoltaic devices.