bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheostatic Regulation of the SERCA/Phospholamban Membrane Protein Complex Using Non-Coding RNA and Single-Stranded DNA oligonucleotides
Authors: Soller Kailey J. , Verardi Raffaello , Jing Meng , Abrol Neha , Yang Jing , Walsh Naomi , Vostrikov Vitaly V. , Robia Seth L. , Bowser Michael T. , Veglia Gianluigi 
Published: August 2015

AbstractThe membrane protein complex between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and phospholamban (PLN) is a prime therapeutic target for reversing cardiac contractile dysfunctions caused by calcium mishandling. So far, however, efforts to develop drugs specific for this protein complex have failed. Here, we show that non-coding RNAs and single-stranded DNAs (ssDNAs) interact with and regulate the function of the SERCA/PLN complex in a tunable manner. Both in HEK cells expressing the SERCA/PLN complex, as well as in cardiac sarcoplasmic reticulum preparations, these short oligonucleotides bind and reverse PLN’s inhibitory effects on SERCA, increasing the ATPase’s apparent Ca2+ affinity. Solid-state NMR experiments revealed that ssDNA interacts with PLN specifically, shifting the conformational equilibrium of the SERCA/PLN complex from an inhibitory to a non-inhibitory state. Importantly, we achieved rheostatic control of SERCA function by modulating the length of ssDNAs. Since restoration of Ca2+ flux to physiological levels represents a viable therapeutic avenue for cardiomyopathies, our results suggest that oligonucleotide-based drugs could be used to fine-tune SERCA function to counterbalance the extent of the pathological insults.
Enhanced marine sulphur emissions offset global warming and impact rainfall
Authors: Grandey B. S. , Wang C. 
Published: August 2015

AbstractArtificial fertilisation of the ocean has been proposed as a possible geoengineering method for removing carbon dioxide from the atmosphere. The associated increase in marine primary productivity may lead to an increase in emissions of dimethyl sulphide (DMS), the primary source of sulphate aerosol over remote ocean regions, potentially causing direct and cloud-related indirect aerosol effects on climate. This pathway from ocean fertilisation to aerosol induced cooling of the climate may provide a basis for solar radiation management (SRM) geoengineering. In this study, we investigate the transient climate impacts of two emissions scenarios: an RCP4.5 (Representative Concentration Pathway 4.5) control; and an idealised scenario, based on RCP4.5, in which DMS emissions are substantially enhanced over ocean areas. We use mini-ensembles of a coupled atmosphere-ocean configuration of CESM1(CAM5) (Community Earth System Model version 1, with the Community Atmosphere Model version 5). We find that the cooling effect associated with enhanced DMS emissions beneficially offsets greenhouse gas induced warming across most of the world. However, the rainfall response may adversely affect water resources, potentially impacting human livelihoods. These results demonstrate that changes in marine phytoplankton activity may lead to a mixture of positive and negative impacts on the climate.
Rapid Particle Patterning in Surface Deposited Micro-Droplets of Low Ionic Content via Low-Voltage Electrochemistry and Electrokinetics
Authors: Sidelman Noam , Cohen Moshik , Kolbe Anke , Zalevsky Zeev , Herrman Andreas , Richter Shachar 
Published: August 2015

AbstractElectrokinetic phenomena are a powerful tool used in various scientific and technological applications for the manipulation of aqueous solutions and the chemical entities within them. However, the use of DC-induced electrokinetics in miniaturized devices is highly limited. This is mainly due to unavoidable electrochemical reactions at the electrodes, which hinder successful manipulation. Here we present experimental evidence that on-chip DC manipulation of particles between closely positioned electrodes inside micro-droplets can be successfully achieved and at low voltages. We show that such manipulation, which is considered practically impossible, can be used to rapidly concentrate and pattern particles in 2D shapes in inter-electrode locations. We show that this is made possible in low ion content dispersions, which enable low-voltage electrokinetics and an anomalous bubble-free water electrolysis. This phenomenon can serve as a powerful tool in both microflow devices and digital microfluidics for rapid pre-concentration and particle patterning.
The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway
Authors: Guven-Maiorov Emine , Keskin Ozlem , Gursoy Attila , VanWaes Carter , Chen Zhong , Tsai Chung-Jung , Nussinov Ruth 
Published: August 2015

AbstractActivated Toll-like receptors (TLRs) cluster in lipid rafts and induce pro- and anti-tumor responses. The organization of the assembly is critical to the understanding of how these key receptors control major signaling pathways in the cell. Although several models for individual interactions were proposed, the entire TIR-domain signalosome architecture has not been worked out, possibly due to its complexity. We employ a powerful algorithm, crystal structures and experimental data to model the TLR4 and its cluster. The architecture that we obtain with 8 MyD88 molecules provides the structural basis for the MyD88-templated myddosome helical assembly and receptor clustering; it also provides clues to pro- and anti-inflammatory signaling pathways branching at the signalosome level to Mal/MyD88 and TRAM/TRIF pro- and anti-inflammatory pathways. The assembly of MyD88 death domain (DD) with TRAF3 (anti-viral/anti-inflammatory) and TRAF6 (pro-inflammatory) suggest that TRAF3/TRAF6 binding sites on MyD88 DD partially overlap, as do IRAK4 and FADD. Significantly, the organization illuminates mechanisms of oncogenic mutations, demonstrates that almost all TLR4 parallel pathways are competitive and clarifies decisions at pathway branching points. The architectures are compatible with the currently-available experimental data and provide compelling insights into signaling in cancer and inflammation pathways.
Carbon dioxide level and form of soil nitrogen regulate assimilation of atmospheric ammonia in young trees
Authors: Silva Lucas C. R. , Salamanca-Jimenez Alveiro , Doane Timothy A. , Horwath William R. 
Published: August 2015

AbstractThe influence of carbon dioxide (CO2) and soil fertility on the physiological performance of plants has been extensively studied, but their combined effect is notoriously difficult to predict. Using Coffea arabica as a model tree species, we observed an additive effect on growth, by which aboveground productivity was highest under elevated CO2 and ammonium fertilization, while nitrate fertilization favored greater belowground biomass allocation regardless of CO2 concentration. A pulse of labelled gases (13CO2 and 15NH3) was administered to these trees as a means to determine the legacy effect of CO2 level and soil nitrogen form on foliar gas uptake and translocation. Surprisingly, trees with the largest aboveground biomass assimilated significantly less NH3 than the smaller trees. This was partly explained by declines in stomatal conductance in plants grown under elevated CO2. However, unlike the 13CO2 pulse, assimilation and transport of the 15NH3 pulse to shoots and roots varied as a function of interactions between stomatal conductance and direct plant response to the form of soil nitrogen, observed as differences in tissue nitrogen content and biomass allocation. Nitrogen form is therefore an intrinsic component of physiological responses to atmospheric change, including assimilation of gaseous nitrogen as influenced by plant growth history.
Population genetic diversity and hybrid detection in captive zebras
Authors: Ito Hideyuki , Langenhorst Tanya , Ogden Rob , Inoue-Murayama Miho 
Published: August 2015

AbstractZebras are members of the horse family. There are three species of zebras: the plains zebra Equus quagga, the Grevy’s zebra E. grevyi and the mountain zebra E. zebra. The Grevy’s zebra and the mountain zebra are endangered and hybridization between the Grevy’s zebra and the plains zebra has been documented, leading to a requirement for conservation genetic management within and between the species. We characterized 28 microsatellite markers in Grevy’s zebra and assessed cross-amplification in plains zebra and two of its subspecies, as well as mountain zebra. A range of standard indices were employed to examine population genetic diversity and hybrid populations between Grevy’s and plains zebra were simulated to investigate subspecies and hybrid detection. Microsatellite marker polymorphism was conserved across species with sufficient variation to enable individual identification in all populations. Comparative diversity estimates indicated greater genetic variation in plains zebra and its subspecies than Grevy’s zebra, despite potential ascertainment bias. Species and subspecies differentiation were clearly demonstrated and F1 and F2 hybrids were correctly identified. These findings provide insights into captive population genetic diversity in zebras and support the use of these markers for identifying hybrids, including the known hybrid issue in the endangered Grevy’s zebra.
Sacrificial adhesive bonding: a powerful method for fabrication of glass microchips
Authors: Lima Renato S. , Leão Paulo A. G. C. , Piazzetta Maria H. O. , Monteiro Alessandra M. , Shiroma Leandro Y. , Gobbi Angelo L. , Carrilho Emanuel 
Published: August 2015

AbstractA new protocol for fabrication of glass microchips is addressed in this research paper. Initially, the method involves the use of an uncured SU-8 intermediate to seal two glass slides irreversibly as in conventional adhesive bonding-based approaches. Subsequently, an additional step removes the adhesive layer from the channels. This step relies on a selective development to remove the SU-8 only inside the microchannel, generating glass-like surface properties as demonstrated by specific tests. Named sacrificial adhesive layer (SAB), the protocol meets the requirements of an ideal microfabrication technique such as throughput, relatively low cost, feasibility for ultra large-scale integration (ULSI) and high adhesion strength, supporting pressures on the order of 5 MPa. Furthermore, SAB eliminates the use of high temperature, pressure, or potential, enabling the deposition of thin films for electrical or electrochemical experiments. Finally, the SAB protocol is an improvement on SU-8-based bondings described in the literature. Aspects such as substrate/resist adherence, formation of bubbles and thermal stress were effectively solved by using simple and inexpensive alternatives.
MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1
Authors: Li Yanan , Mao Ling , Gao Yuan , Baral Suraj , Zhou Yifan , Hu Bo 
Published: August 2015

AbstractPrevious studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.
Local coordination state of rare earth in eutectic scintillators for neutron detector applications
Authors: Masai Hirokazu , Yanagida Takayuki , Mizoguchi Teruyasu , Ina Toshiaki , Miyazaki Takamichi , Kawaguti Noriaki , Fukuda Kentaro 
Published: August 2015

AbstractAtomic distribution in phosphors for neutron detection has not been fully elucidated, although their ionization efficiency is strongly dependent on the state of the rare earth in the matrix. In this work, we examine optical properties of Eu-doped 80LiF-20CaF2 eutectics for neutron detector applications based on the Eu distribution. At low concentrations, aggregation of Eu cations is observed, whereas homogeneous atomic dispersion in the CaF2 layer, to substitute Ca2+ ions, is observed in the eutectics at high concentrations. Eu LIII edge X-ray absorption fine structure (XAFS) analysis suggests that neutron responses do not depend on the amount of Eu2+ ions. However, transparency, which depends on an ordered lamellar structure, is found to be important for a high light yield in neutron detection. The results confirm the effectiveness of the basic idea concerning the separation of radiation absorbers and activators in particle radiation scintillation and present potential for further improvement of novel bulk detectors.
Efficient CRISPR/Cas9-mediated biallelic gene disruption and site-specific knockin after rapid selection of highly active sgRNAs in pigs
Authors: Wang Xianlong , Zhou Jinwei , Cao Chunwei , Huang Jiaojiao , Hai Tang , Wang Yanfang , Zheng Qiantao , Zhang Hongyong , Qin Guosong , Miao Xiangnan , Wang Hongmei , Cao Suizhong , Zhou Qi , Zhao Jianguo 
Published: August 2015

AbstractGenetic engineering in livestock was greatly enhanced by the emergence of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), which can be programmed with a single-guide RNA (sgRNA) to generate site-specific DNA breaks. However, the uncertainties caused by wide variations in sgRNA activity impede the utility of this system in generating genetically modified pigs. Here, we described a single blastocyst genotyping system to provide a simple and rapid solution to evaluate and compare the sgRNA efficiency at inducing indel mutations for a given gene locus. Assessment of sgRNA mutagenesis efficiencies can be achieved within 10 days from the design of the sgRNA. The most effective sgRNA selected by this system was successfully used to induce site-specific insertion through homology-directed repair at a frequency exceeding 13%. Additionally, the highly efficient gene deletion via the selected sgRNA was confirmed in pig fibroblast cells, which could serve as donor cells for somatic cell nuclear transfer. We further showed that direct cytoplasmic injection of Cas9 mRNA and the favorable sgRNA into zygotes could generate biallelic knockout piglets with an efficiency of up to 100%. Thus, our method considerably reduces the uncertainties and expands the practical possibilities of CRISPR/Cas9-mediated genome engineering in pigs.
Myth busting? Effects of embryo positioning and egg turning on hatching success in the water snake Natrix maura
Authors: Aubret Fabien , Blanvillain Gaëlle , Kok Philippe J. R. 
Published: August 2015

AbstractIt is a common belief that reptile eggs should not be turned after oviposition once the embryo has attached itself to the inner membrane of the shell as it might kill developing embryos. Here, we used 338 eggs from 32 clutches of the water snake Natrix maura to (1) thoroughly describe natural clutch arrangement, (2) experimentally assess the effects of natural embryo positioning and (3) egg turning on embryo metabolism, hatching success and hatchling phenotype. Clutches contained, on average, 59% of embryos located at the top, 28% at the bottom and 14% on a side of the egg. Larger females laid larger clutches with higher proportion of top located embryos. Top embryos displayed higher metabolic rates (heart rates), shorter incubation time and produced lighter and shorter snakes than bottom embryos. Egg turning did not significantly influence egg development, hatching success or hatchling phenotypes. However, post-birth mortality was significantly higher in turned (37.5%) compared to unturned (4.5%) embryos, providing support to the common belief that eggs should not be moved from their natural position.
CNV Analysis Associates AKNAD1 with Type-2 Diabetes in Jordan Subpopulations
Authors: Dajani Rana , Li Jin , Wei Zhi , Glessner Joseph T. , Chang Xiao , Cardinale Christopher J. , Pellegrino Renata , Wang Tiancheng , Hakooz Nancy , Khader Yousef , Sheshani Amina , Zandaki Duaa , Hakonarson Hakon 
Published: August 2015

AbstractPrevious studies have identified a number of single nucleotide polymorphisms (SNPs) associated with type-2 diabetes (T2D), but copy number variation (CNV) association has rarely been addressed, especially in populations from Jordan. To investigate CNV associations for T2D in populations in Jordan, we conducted a CNV analysis based on intensity data from genome-wide SNP array, including 34 T2D cases and 110 healthy controls of Chechen ethnicity, as well as 34 T2D cases and 106 healthy controls of Circassian ethnicity. We found a CNV region in protein tyrosine phosphatase receptor type D (PTPRD) with significant association with T2D. PTPRD has been reported to be associated with T2D in genome-wide association studies (GWAS). We additionally identified 16 CNV regions associated with T2D which overlapped with gene exons. Of particular interest, a CNV region in the gene AKNA Domain Containing 1 (AKNAD1) surpassed the experiment-wide significance threshold. Endoplasmic reticulum (ER)-related pathways were significantly enriched among genes which are predicted to be functionally associated with human or mouse homologues of AKNAD1. This is the first CNV analysis of a complex disease in populations of Jordan. We identified and experimentally validated a significant CNVR in gene AKNAD1 associated with T2D.
Large-scale RNA-Seq Transcriptome Analysis of 4043 Cancers and 548 Normal Tissue Controls across 12 TCGA Cancer Types
Authors: Peng Li , Bian Xiu Wu , Li Di Kang , Xu Chuan , Wang Guang Ming , Xia Qing You , Xiong Qing 
Published: August 2015

AbstractThe Cancer Genome Atlas (TCGA) has accrued RNA-Seq-based transcriptome data for more than 4000 cancer tissue samples across 12 cancer types, translating these data into biological insights remains a major challenge. We analyzed and compared the transcriptomes of 4043 cancer and 548 normal tissue samples from 21 TCGA cancer types and created a comprehensive catalog of gene expression alterations for each cancer type. By clustering genes into co-regulated gene sets, we identified seven cross-cancer gene signatures altered across a diverse panel of primary human cancer samples. A 14-gene signature extracted from these seven cross-cancer gene signatures precisely differentiated between cancerous and normal samples, the predictive accuracy of leave-one-out cross-validation (LOOCV) were 92.04%, 96.23%, 91.76%, 90.05%, 88.17%, 94.29% and 99.10% for BLCA, BRCA, COAD, HNSC, LIHC, LUAD and LUSC, respectively. A lung cancer-specific gene signature, containing SFTPA1 and SFTPA2 genes, accurately distinguished lung cancer from other cancer samples, the predictive accuracy of LOOCV for TCGA and GSE5364 data were 95.68% and 100%, respectively. These gene signatures provide rich insights into the transcriptional programs that trigger tumorigenesis and metastasis and many genes in the signature gene panels may be of significant value to the diagnosis and treatment of cancer.
A novel cell-printing method and its application to hepatogenic differentiation of human adipose stem cell-embedded mesh structures
Authors: Ahn Seung Hyun , Lee Hyeong Jin , Lee Ji-Seon , Yoon Hyeon , Chun Wook , Kim Geun Hyung 
Published: August 2015

AbstractWe report a cell-dispensing technique, using a core–shell nozzle and an absorbent dispensing stage to form cell-embedded struts. In the shell of the nozzle, a cross-linking agent flowed continuously onto the surface of the dispensed bioink in the core nozzle, so that the bioink struts were rapidly gelled and any remnant cross-linking solution during the process was rapidly absorbed into the working stage, resulting in high cell-viability in the bioink strut and stable formation of a three-dimensional mesh structure. The cell-printing conditions were optimized by manipulating the process conditions to obtain high mechanical stability and high cell viability. The cell density was 1 × 107 mL−1, which was achieved using a 3-wt% solution of alginate in phosphate-buffered saline, a mass fraction of 1.2 wt% of CaCl2 flowing in the shell nozzle with a fixed flow rate of 0.08 mL min−1 and a translation velocity of the printing nozzle of 10 mm s−1. To demonstrate the applicability of the technique, preosteoblasts and human adipose stem cells (hASCs) were used to obtain cell-laden structures with multi-layer porous mesh structures. The fabricated cell-laden mesh structures exhibited reasonable initial cell viabilities for preosteoblasts (93%) and hASCs (92%) and hepatogenic differentiation of hASC was successfully achieved.
Social distance and anonymity modulate fairness consideration: An ERP study
Authors: Yu Rongjun , Hu Pan , Zhang Ping 
Published: August 2015

AbstractPrevious research indicated that fairness consideration can be influenced by social distance. However, it is not clear whether social distance and anonymity have an interactive impact on fairness evaluation during asset distribution and whether these processes can be documented in brain activity. Using a modified ultimatum game combined with measures of event related potential (ERP), we examined how social distance and anonymity modulate brain response to inequality. At the behavior level, we found that acceptance rate and reaction time can be substantially modified by social distance and anonymity. Feedback-related negativity, an ERP component associated with conflict between cognitive and emotion motives, was more negative in response to unfairness than fairness from strangers; however, it showed an opposite trend for unfair offers provided by friends, suggesting that the influence of social distance on fairness perception is relatively fast. The P300 in response to fair offers was more positive when the proposers made offers when uncertain about partner identity than when certain about partner identity. These results suggest that unfairness is evaluated in a fast conflict detection stage and a slower stage that integrates more complex social contextual factors such as anonymity.
Chimpanzee lip-smacking facilitates cooperative behaviour
Authors: Fedurek Pawel , Slocombe Katie E. , Hartel Jessica A. , Zuberbühler Klaus 
Published: August 2015

AbstractSignalling plays an important role in facilitating and maintaining affiliative or cooperative interactions in social animals. Social grooming in primates is an example of an interaction that requires coordination between partners but little is known about communicative behaviours facilitating this activity. In this study, we analysed the communication of wild chimpanzees of Budongo Forest, Uganda, as they entered and maintained a naturally occurring cooperative interaction: social grooming. We found that lip-smacking, a distinct multimodal oral gesture produced during grooming, coordinated this activity. Lip-smacking at the beginning of grooming bouts was significantly more often followed by longer and reciprocated bouts than silent grooming initiations. Lip-smacks were more likely to be produced when the risk of termination of the interaction by the recipient was high, for instance when grooming vulnerable body parts. Groomers were also more likely to produce lip-smacks during face-to-face grooming where the visual aspect of the signal could be perceived. Data are consistent with the hypothesis that chimpanzee lip-smacks function to coordinate and prolong social grooming, suggesting that this oral signal is an example of a communicative behaviour facilitating cooperative behaviour in chimpanzees.