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Sample records for micrornas show mutually

  1. MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration.

    PubMed

    Liu, Chang-Mei; Wang, Rui-Ying; Saijilafu; Jiao, Zhong-Xian; Zhang, Bo-Yin; Zhou, Feng-Quan

    2013-07-01

    Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.

  2. An evolutionarily conserved mutual interdependence between Aire and microRNAs in promiscuous gene expression.

    PubMed

    Ucar, Olga; Tykocinski, Lars-Oliver; Dooley, James; Liston, Adrian; Kyewski, Bruno

    2013-07-01

    The establishment and maintenance of central tolerance depends to a large extent on the ability of medullary thymic epithelial cells to express a variety of tissue-restricted antigens, the so-called promiscuous gene expression (pGE). Autoimmune regulator (Aire) is to date the best characterised transcriptional regulator known to at least partially coordinate pGE. There is accruing evidence that the expression of Aire-dependent and -independent genes is modulated by higher order chromatin configuration, epigenetic modifications and post-transcriptional control. Given the involvement of microRNAs (miRNAs) as potent post-transcriptional modulators of gene expression, we investigated their role in the regulation of pGE in purified mouse and human thymic epithelial cells (TECs). Microarray profiling of TEC subpopulations revealed evolutionarily conserved cell type and differentiation-specific miRNA signatures with a subset of miRNAs being significantly upregulated during terminal medullary thymic epithelial cell differentiation. The differential regulation of this subset of miRNAs was correlated with Aire expression and some of these miRNAs were misexpressed in the Aire knockout thymus. In turn, the specific absence of miRNAs in TECs resulted in a progressive reduction of Aire expression and pGE, affecting both Aire-dependent and -independent genes. In contrast, the absence of miR-29a only affected the Aire-dependent gene pool. These findings reveal a mutual interdependence of miRNA and Aire. © 2013 The Authors. European Journal of Immunology published byWiley-VCH Verlag GmbH & Co. KGaA Weinheim.

  3. A spatial model showing differences between juxtacrine and paracrine mutual oocyte-granulosa cells interactions.

    PubMed

    Saadeldin, Islam M; Elsayed, Asmaa; Kim, Su Jin; Moon, Joon Hu; Lee, Byeong Chun

    2015-02-01

    The bidirectional communication between oocytes and granulosa cells are mediated by several factors via a local feedback loop(s). The current model was carried out to study the spatial mutual interaction of porcine denuded oocytes and granulosa cells either in direct contact (juxtacrine) or paracrine co-culture using transwell system. Transwell 0.4 μm polyester membrane inserts were used to permit oocytes-granulosa cells paracrine communication with a distance of 2 mm between them in co-culture. Oocytes were cultured with granulosa cells in a defined basic maturation medium for 44 h. In results, oocyte secreted factors (OSFs; GDF9 and BMP15) temporal expression showed progressive decrement by the end of culture in case of direct contact with granulosa cells while it was increased progressively in the paracrine co-culture groups. However, oocytes that were cultured in direct contact showed a significant increase in blastocyst development after parthenogenetic activation than the paracrine co-cultured ones (20% vs. 11.5%, respectively). By the end of culture, granulosa cell count in direct contact showed a significant decrease than the indirect co-culture group (1.2 x 105 cell/mL vs. 2.1 x 10(5) cell/mL, respectively). Steroids (P4 and E2) and steriodogenesis enzymes mRNA levels showed significant temporal alterations either after 22 h and 44 h of IVM in both juxtacrine and paracrine co-culture systems (P ≤ 0.05). CX43 was much more highly expressed in the granulosa of the direct contact group than the indirect co-culture group. These results indicate the difference in mutual communication between oocytes and granulosa cells that were cocultured either in direct contact (juxtacrine) or with a short distance (paracrine) and propose a new paradigm to study different ovarian follicular cells interaction.

  4. A simple coculture system shows mutualism between anaerobic faecalibacteria and epithelial Caco-2 cells.

    PubMed

    Sadaghian Sadabad, Mehdi; von Martels, Julius Z H; Khan, Muhammed Tanweer; Blokzijl, Tjasso; Paglia, Giuseppe; Dijkstra, Gerard; Harmsen, Hermie J M; Faber, Klaas Nico

    2015-12-15

    Most gut bacteria are obligate anaerobes and are important for human health. However, little mechanistic insight is available on the health benefits of specific anaerobic gut bacteria. A main obstacle in generating such knowledge is the lack of simple and robust coculturing methods for anaerobic bacteria and oxygen-requiring human cells. Here, we describe the development of a coculture system for intestinal Caco-2 cells and an anaerobic symbiont, Faecalibacterium prausnitzii, making use of 50 mL culture tubes. F. prausnitzii was grown in 40 mL YCFAG-agar with glass-adhered Caco-2 cells placed on top in 10 mL DMEM medium. Grown for 18-36 h in a humidified incubator at 37 °C and 5% CO2, coverslip-attached Caco-2 cells promoted growth and metabolism of F. prausnitzii, while F. prausnitzii suppressed inflammation and oxidative stress in Caco-2 cells. F. prausnitzii did not compromise Caco-2 cell viability. Exogenously added porcine mucin also promoted growth of F. prausnitzii, suggesting that it may be part of the mechanism of Caco-2-stimulated growth of F. prausnitzii. This 'Human oxygen-Bacteria anaerobic' (HoxBan) coculturing system uniquely establishes host-microbe mutualism of a beneficial anaerobic gut microbe in vitro and principally allows the analysis of host-microbe interactions of pure and mixed cultures of bacteria and human cells.

  5. Modulation of microRNAs in two genetically disparate chicken lines showing different necrotic enteritis disease susceptibility

    USDA-ARS?s Scientific Manuscript database

    MicroRNAs (miRNA) play a critical role in post-transcriptional regulation by influencing the 3'-UTR of target genes. Using two inbred White Leghorn chicken lines, line 6.3 and line 7.2 showing Marek’s disease-resistant and -susceptible phenotypes, respectively, we used small RNA high-throughput sequ...

  6. Syncytiotrophoblast vesicles show altered micro-RNA and haemoglobin content after ex-vivo perfusion of placentas with haemoglobin to mimic preeclampsia.

    PubMed

    Cronqvist, Tina; Saljé, Karen; Familari, Mary; Guller, Seth; Schneider, Henning; Gardiner, Chris; Sargent, Ian L; Redman, Christopher W; Mörgelin, Matthias; Åkerström, Bo; Gram, Magnus; Hansson, Stefan R

    2014-01-01

    Cell-free foetal haemoglobin (HbF) has been shown to play a role in the pathology of preeclampsia (PE). In the present study, we aimed to further characterize the harmful effects of extracellular free haemoglobin (Hb) on the placenta. In particular, we investigated whether cell-free Hb affects the release of placental syncytiotrophoblast vesicles (STBMs) and their micro-RNA content. The dual ex-vivo perfusion system was used to perfuse isolated cotyledons from human placenta, with medium alone (control) or supplemented with cell-free Hb. Perfusion medium from the maternal side of the placenta was collected at the end of all perfusion phases. The STBMs were isolated using ultra-centrifugation, at 10,000×g and 150,000×g (referred to as 10K and 150K STBMs). The STBMs were characterized using the nanoparticle tracking analysis, identification of surface markers and transmission electron microscopy. RNA was extracted and nine different micro-RNAs, related to hypoxia, PE and Hb synthesis, were selected for analysis by quantitative PCR. All micro-RNAs investigated were present in the STBMs. Mir-517a, mir-141 and mir-517b were down regulated after Hb perfusion in the 10K STBMs. Furthermore, Hb was shown to be carried by the STBMs. This study showed that Hb perfusion can alter the micro-RNA content of released STBMs. Of particular interest is the alteration of two placenta specific micro-RNAs; mir-517a and mir-517b. We have also seen that STBMs may function as carriers of Hb into the maternal circulation.

  7. MicroRNA Expression Shows Inflammatory Dysregulation and Tumor-Like Proliferative Responses in Joints of Patients With Postinfectious Lyme Arthritis.

    PubMed

    Lochhead, Robert B; Strle, Klemen; Kim, Nancy D; Kohler, Minna J; Arvikar, Sheila L; Aversa, John M; Steere, Allen C

    2017-05-01

    Lyme arthritis (LA) is caused by infection with Borrelia burgdorferi and usually resolves following spirochetal killing with antibiotics. However, in some patients, arthritis persists after antibiotic therapy. To provide insights into underlying pathogenic processes associated with antibiotic-refractory LA (postinfectious LA), we analyzed differences in microRNA (miRNA) expression between LA patients with active infection and those with postinfectious LA. MicroRNA expression was assayed in synovial fluid (SF) from LA patients before and after oral and intravenous antibiotic therapy, and in synovial tissue obtained months after antibiotic therapy from patients with postinfectious LA. SF and tissue from patients with other forms of arthritis, such as rheumatoid arthritis (RA) and osteoarthritis, were used for comparison. SF from LA patients during active infection had marked elevations of white blood cells, particularly polymorphonuclear leukocytes, accompanied by elevated levels of microRNA-223 (miR-223). In contrast, SF from postantibiotic LA patients contained greater percentages of lymphocytes and mononuclear cells. SF from postantibiotic LA patients also exhibited marked inflammatory (miR-146a, miR-155), wound repair (miR-142), and proliferative (miR-17-92) miRNA signatures, and higher levels of these miRNAs correlated with longer arthritis duration. Levels of miR-146a, miR-155, miR-142, miR-223, and miR-17-92 were also elevated in synovial tissue in late postinfectious LA, and levels of let-7a were reduced, similar to RA. During active infection, miRNA expression in SF reflected an immune response associated with bacterial killing, while in postinfectious LA, miRNA expression in SF and synovial tissue reflected chronic inflammation, synovial proliferation, and breakdown of wound repair processes, showing that the nature of the arthritis was altered after spirochetal killing. © 2017, American College of Rheumatology.

  8. Effective Anti-miRNA Oligonucleotides Show High Releasing Rate of MicroRNA from RNA-Induced Silencing Complex.

    PubMed

    Ariyoshi, Jumpei; Matsuyama, Yohei; Kobori, Akio; Murakami, Akira; Sugiyama, Hiroshi; Yamayoshi, Asako

    2017-10-01

    MicroRNAs (miRNAs) regulate gene expression by forming RNA-induced silencing complexes (RISCs) and have been considered as promising therapeutic targets. MiRNA is an essential component of RISC for the modulation of gene expression. Therefore, the release of miRNA from RISC is considered as an effective method for the inhibition of miRNA functions. In our previous study, we reported that anti-miRNA oligonucleotides (AMOs), which are composed of the 2'-O-methyl (2'-OMe) RNA, could induce the release of miRNA from RISC. However, the mechanisms underlying the miRNA-releasing effects of chemically modified AMOs, which are conventionally used as anti-cancer drugs, are still unclear. In this study, we investigated the relationship between the miRNA releasing rate from RISC and the inhibitory effect on RISC activity (IC50) using conventional chemically modified AMOs. We demonstrated that the miRNA-releasing effects of AMOs are directly proportional to the IC50 values, and AMOs, which have an ability to promote the release of miRNA from RISC, can effectively inhibit RISC activity in living cells.

  9. Intraguild mutualism.

    PubMed

    Crowley, Philip H; Cox, John J

    2011-12-01

    Although studies of species linked by a common resource (i.e. ecological guilds) have so far mainly focused on competition and predation, guilds are also good places to find mutualism. In this review we consider some three- and four-species community modules to illustrate examples of wide relevance. Mutualism arises from various direct and indirect trophic and non-trophic interactions between species--and within modules both with and without intraguild predation. Species removal and augmentation experiments, other manipulations, direct measurements, and path-analytic methods can determine the presence and intensity of mutualism within guilds. Such studies, particularly when associated with existing theory and new theoretical development, can help advance an interaction-based approach to community analysis that recognizes linkages among mutualism, predation and competition in natural systems.

  10. Mutual information algorithms

    NASA Astrophysics Data System (ADS)

    Jiang, Ai-Hua; Huang, Xiu-Chang; Zhang, Zhen-Hua; Li, Jun; Zhang, Zhi-Yi; Hua, Hong-Xin

    2010-11-01

    Three new mutual information algorithms are raised for time delay in the phase space reconstruction process. Firstly, Cellucci's mutual information algorithm is analyzed based on partitioning plane, which is constructed by a pair of Lorenz series with the same size, into four and sixteen grids with equal distribution probability in elements on each axis. Then three new mutual information algorithms are promoted based on the original probability matrix that shows the distribution of points corresponding to the data pairs of Lorenz series on the plane, the matrix excluding the last column and the last row of the original one as well as the proportionally revised matrix from the original one. Synchronously, an algorithm to compute the probability matrix is also advanced by sorting two series and replacing each numerical value with its order number in its own series so as to judge the element in which data sets are located. The optimal time delay of the three new mutual information algorithms as well as the computing time is also compared when series sizes are different. Finally, after reconstructing phase space with the optimal time delay, comparison between the maximal Lyapunov exponent calculated by Rosenstein's algorithm from time series and that gained by Jacobi matrix from Lorenz equation is used to confirm the validity of the new mutual information algorithms. The results show that Cellucci's mutual information algorithm will lead to wrong optimal time delay when series size is not a multiple of elements. The three new algorithms, whose results are more steady when a large number of data pairs are used, can not only eliminate the default of Cellucci's algorithm but also is very speedy, and the time spent on calculations by three algorithms nearly enhances linearly with the increase in series size. Moreover, the algorithm using original probability distribution matrix is more accurate than the others when small size series are used, and is also faster than the

  11. Diverse correlation patterns between microRNAs and their targets during tomato fruit development indicates different modes of microRNA actions.

    PubMed

    Lopez-Gomollon, Sara; Mohorianu, Irina; Szittya, Gyorgy; Moulton, Vincent; Dalmay, Tamas

    2012-12-01

    MicroRNAs negatively regulate the accumulation of mRNAs therefore when they are expressed in the same cells their expression profiles show an inverse correlation. We previously described one positively correlated miRNA/target pair, but it is not known how widespread this phenomenon is. Here, we investigated the correlation between the expression profiles of differentially expressed miRNAs and their targets during tomato fruit development using deep sequencing, Northern blot and RT-qPCR. We found an equal number of positively and negatively correlated miRNA/target pairs indicating that positive correlation is more frequent than previously thought. We also found that the correlation between microRNA and target expression profiles can vary between mRNAs belonging to the same gene family and even for the same target mRNA at different developmental stages. Since microRNAs always negatively regulate their targets, the high number of positively correlated microRNA/target pairs suggests that mutual exclusion could be as widespread as temporal regulation. The change of correlation during development suggests that the type of regulatory circuit directed by a microRNA can change over time and can be different for individual gene family members. Our results also highlight potential problems for expression profiling-based microRNA target identification/validation.

  12. microRNA-454 shows anti-angiogenic and anti-metastatic activity in pancreatic ductal adenocarcinoma by targeting LRP6

    PubMed Central

    Fan, Yue; Shi, Chenye; Li, Tianyu; Kuang, Tiantao

    2017-01-01

    Our previous work has shown that microRNA-454 (miR-454) can inhibit the growth of pancreatic ductal adenocarcinoma (PDAC) by blocking the recruitment of bone marrow-derived macrophages. In the present study, we aimed to explore its role in the proliferation, invasion, and pro-angiogenic activity of PDAC cells in vitro and lung metastasis in vivo. PANC-1 and MiaPaCa-2 cells were transfected with a miR-454-expressing plasmid and tested for cell proliferation, colony formation, cell cycle distribution, invasion, and pro-angiogenic activity. The target gene(s) that mediated the action of miR-454 was identified. The effect of miR-454 overexpression on lung metastasis of PDAC was evaluated in nude mice. Of note, overexpression of miR-454 significantly inhibited PDAC cell proliferation and colony formation and arrests PDAC cells at the G2/M phase. Decreased invasiveness was observed in miR-454-overexpressing PDAC cells. Conditioned media from miR-454-overexpressing PANC-1 cells contained lower levels of vascular endothelial growth factor and had reduced capacity to induce endothelial cell tube-like structure formation. Mechanistically, miR-454 was found to target the mRNA of LRP6 and inhibit the activation of Wnt/β-catenin signaling in PDAC cells. Ectopic expression of LRP6 significantly reversed the suppressive effects of miR-454 on PDAC cells. In vivo studies confirmed that miR-454-overexpressing PANC-1 cells formed significantly less lung metastases than control cells. Altogether, miR-454 functions as a suppressor in tumor growth, angiogenesis, and metastasis in PDAC, likely through downregulation of LRP6. PMID:28123855

  13. Uncertainty relation for mutual information

    NASA Astrophysics Data System (ADS)

    Schneeloch, James; Broadbent, Curtis J.; Howell, John C.

    2014-12-01

    We postulate the existence of a universal uncertainty relation between the quantum and classical mutual informations between pairs of quantum systems. Specifically, we propose that the sum of the classical mutual information, determined by two mutually unbiased pairs of observables, never exceeds the quantum mutual information. We call this the complementary-quantum correlation (CQC) relation and prove its validity for pure states, for states with one maximally mixed subsystem, and for all states when one measurement is minimally disturbing. We provide results of a Monte Carlo simulation suggesting that the CQC relation is generally valid. Importantly, we also show that the CQC relation represents an improvement to an entropic uncertainty principle in the presence of a quantum memory, and that it can be used to verify an achievable secret key rate in the quantum one-time pad cryptographic protocol.

  14. Deep sequencing shows microRNA involvement in bovine mammary gland adaptation to diets supplemented with linseed oil or safflower oil.

    PubMed

    Li, Ran; Beaudoin, Frédéric; Ammah, Adolf A; Bissonnette, Nathalie; Benchaar, Chaouki; Zhao, Xin; Lei, Chuzhao; Ibeagha-Awemu, Eveline M

    2015-10-30

    Bovine milk fat composition is responsive to dietary manipulation providing an avenue to modify the content of fatty acids and especially some specific unsaturated fatty acid (USFA) isomers of benefit to human health. MicroRNAs (miRNAs) regulate gene expression but their specific roles in bovine mammary gland lipogenesis are unclear. The objective of this study was to determine the expression pattern of miRNAs following mammary gland adaptation to dietary supplementation with 5 % linseed or safflower oil using next generation RNA-sequencing. Twenty-four Canadian Holstein dairy cows (twelve per treatment) in mid lactation were fed a control diet (total mixed ration of corn:grass silages) for 28 days followed by a treatment period (control diet supplemented with 5 % linseed or safflower oil) of 28 days. Milk samples were collected weekly for fat and individual fatty acid determination. RNA from mammary gland biopsies harvested on day-14 (control period) and on days +7 and +28 (treatment period) from six randomly selected cows per treatment was subjected to small RNA sequencing. Milk fat percentage decreased significantly (P < 0.001) during treatment with the two diets as compared to the control period. The individual saturated fatty acids C4:0, C6:0, C8:0, C14:0 and C16:0 decreased significantly (P < 0.05) while five USFAs (C14:1, C18:1n11t, C20:3n3, C20:5n3 and CLA:t10c12) increased remarkably (P < 0.05) in response to both treatments. Analysis of 361 million sequence reads generated 321 known bovine miRNAs and 176 novel miRNAs. The expression of fourteen and twenty-two miRNAs was affected (P < 0.05) by linseed and safflower oil treatments, respectively. Seven miRNAs including six up-regulated (bta-miR-199c, miR-199a-3p, miR-98, miR-378, miR-148b and miR-21-5p) and one down-regulated (bta-miR-200a) were found to be regulated (P < 0.05) by both treatments, and thus considered core differentially expressed (DE) miRNAs. The gene targets of core DE miRNAs have functions

  15. Cheaters in mutualism networks.

    PubMed

    Genini, Julieta; Morellato, L Patrícia C; Guimarães, Paulo R; Olesen, Jens M

    2010-08-23

    Mutualism-network studies assume that all interacting species are mutualistic partners and consider that all links are of one kind. However, the influence of different types of links, such as cheating links, on network organization remains unexplored. We studied two flower-visitation networks (Malpighiaceae and Bignoniaceae and their flower visitors), and divide the types of link into cheaters (i.e. robbers and thieves of flower rewards) and effective pollinators. We investigated if there were topological differences among networks with and without cheaters, especially with respect to nestedness and modularity. The Malpighiaceae network was nested, but not modular, and it was dominated by pollinators and had much fewer cheater species than Bignoniaceae network (28% versus 75%). The Bignoniaceae network was mainly a plant-cheater network, being modular because of the presence of pollen robbers and showing no nestedness. In the Malpighiaceae network, removal of cheaters had no major consequences for topology. In contrast, removal of cheaters broke down the modularity of the Bignoniaceae network. As cheaters are ubiquitous in all mutualisms, the results presented here show that they have a strong impact upon network topology.

  16. Cheaters in mutualism networks

    PubMed Central

    Genini, Julieta; Morellato, L. Patrícia C.; Guimarães, Paulo R.; Olesen, Jens M.

    2010-01-01

    Mutualism-network studies assume that all interacting species are mutualistic partners and consider that all links are of one kind. However, the influence of different types of links, such as cheating links, on network organization remains unexplored. We studied two flower-visitation networks (Malpighiaceae and Bignoniaceae and their flower visitors), and divide the types of link into cheaters (i.e. robbers and thieves of flower rewards) and effective pollinators. We investigated if there were topological differences among networks with and without cheaters, especially with respect to nestedness and modularity. The Malpighiaceae network was nested, but not modular, and it was dominated by pollinators and had much fewer cheater species than Bignoniaceae network (28% versus 75%). The Bignoniaceae network was mainly a plant–cheater network, being modular because of the presence of pollen robbers and showing no nestedness. In the Malpighiaceae network, removal of cheaters had no major consequences for topology. In contrast, removal of cheaters broke down the modularity of the Bignoniaceae network. As cheaters are ubiquitous in all mutualisms, the results presented here show that they have a strong impact upon network topology. PMID:20089538

  17. The evolution of mutualism.

    PubMed

    Leigh, E G

    2010-12-01

    Like altruism, mutualism, cooperation between species, evolves only by enhancing all participants' inclusive fitness. Mutualism evolves most readily between members of different kingdoms, which pool complementary abilities for mutual benefit: some of these mutualisms represent major evolutionary innovations. Mutualism cannot persist if cheating annihilates its benefits. In long-term mutualisms, symbioses, at least one party associates with the other nearly all its life. Usually, a larger host harbours smaller symbionts. Cheating is restrained by vertical transmission, as in Buchnera; partner fidelity, as among bull-thorn acacias and protective ants; test-based choice of symbionts, as bobtail squid choose bioluminescent bacteria; or sanctioning nonperforming symbionts, as legumes punish nonperforming nitrogen-fixing bacteria. Mutualisms involving brief exchanges, as among plants and seed-dispersers, however, persist despite abundant cheating. Both symbioses and brief-exchange mutualisms have transformed whole ecosystems. These mutualisms may be steps towards ecosystems which, like Adam Smith's ideal economy, serve their members' common good. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

  18. Covariant mutually unbiased bases

    NASA Astrophysics Data System (ADS)

    Carmeli, Claudio; Schultz, Jussi; Toigo, Alessandro

    2016-06-01

    The connection between maximal sets of mutually unbiased bases (MUBs) in a prime-power dimensional Hilbert space and finite phase-space geometries is well known. In this article, we classify MUBs according to their degree of covariance with respect to the natural symmetries of a finite phase-space, which are the group of its affine symplectic transformations. We prove that there exist maximal sets of MUBs that are covariant with respect to the full group only in odd prime-power dimensional spaces, and in this case, their equivalence class is actually unique. Despite this limitation, we show that in dimension 2r covariance can still be achieved by restricting to proper subgroups of the symplectic group, that constitute the finite analogues of the oscillator group. For these subgroups, we explicitly construct the unitary operators yielding the covariance.

  19. Comparison of microRNA expression levels between initial and recurrent glioblastoma specimens.

    PubMed

    Ilhan-Mutlu, Aysegül; Wöhrer, Adelheid; Berghoff, Anna Sophie; Widhalm, Georg; Marosi, Christine; Wagner, Ludwig; Preusser, Matthias

    2013-05-01

    Glioblastoma is the most frequent primary brain tumour in adults. Recent therapeutic advances increased patient's survival, but tumour recurrence inevitably occurs. The pathobiological mechanisms involved in glioblastoma recurrence are still unclear. MicroRNAs are small RNAs proposed o have important roles for cancer including proliferation, aggressiveness and metastases development. There exist only few data on the involvement of microRNAs in glioblastoma recurrence. We selected the following 7 microRNAs with potential relevance for glioblastoma pathobiology by means of a comprehensive literature search: microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222. We further selected 15 primary glioblastoma patients, of whom formalin fixed and paraffin embedded tissue (FFPE) of the initial and recurrence surgery were available. All patients had received first line treatment consisting of postoperative combined radiochemotherapy with temozolomide (n = 15). Non-neoplastic brain tissue samples from 3 patients with temporal lobe epilepsy served as control. The expression of the microRNAs were analysed by RT-qPCR. These were correlated with each other and with clinical parameters. All microRNAs showed detectable levels of expressions in glioblastoma group, whereas microRNA-10b was not detectable in epilepsy patients. MicroRNAs except microRNA-21 showed significantly higher levels in epilepsy patients when compared to the levels of first resection of glioblastoma. Comparison of microRNA levels between first and second resections revealed no significant change. Cox regression analyses showed no significant association of microRNA expression levels in the tumor tissue with progression free survival times. Expression levels of microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222 do not differ significantly between initial and recurrent glioblastoma.

  20. Construction of bacteria-eukaryote synthetic mutualism.

    PubMed

    Kubo, Isao; Hosoda, Kazufumi; Suzuki, Shingo; Yamamoto, Kayo; Kihara, Kumiko; Mori, Kotaro; Yomo, Tetsuya

    2013-08-01

    Mutualism is ubiquitous in nature but is known to be intrinsically vulnerable with regard to both population dynamics and evolution. Synthetic ecology has indicated that it is feasible for organisms to establish novel mutualism merely through encountering each other by showing that it is feasible to construct synthetic mutualism between organisms. However, bacteria-eukaryote mutualism, which is ecologically important, has not yet been constructed. In this study, we synthetically constructed mutualism between a bacterium and a eukaryote by using two model organisms. We mixed a bacterium, Escherichia coli (a genetically engineered glutamine auxotroph), and an amoeba, Dictyostelium discoideum, in 14 sets of conditions in which each species could not grow in monoculture but potentially could grow in coculture. Under a single condition in which the bacterium and amoeba mutually compensated for the lack of required nutrients (lipoic acid and glutamine, respectively), both species grew continuously through several subcultures, essentially establishing mutualism. Our results shed light on the establishment of bacteria-eukaryote mutualism and indicate that a bacterium and eukaryote pair in nature also has a non-negligible possibility of establishing novel mutualism if the organisms are potentially mutualistic.

  1. Mutually Exclusive Uncertainty Relations

    PubMed Central

    Xiao, Yunlong; Jing, Naihuan

    2016-01-01

    The uncertainty principle is one of the characteristic properties of quantum theory based on incompatibility. Apart from the incompatible relation of quantum states, mutually exclusiveness is another remarkable phenomenon in the information- theoretic foundation of quantum theory. We investigate the role of mutual exclusive physical states in the recent work of stronger uncertainty relations for all incompatible observables by Mccone and Pati and generalize the weighted uncertainty relation to the product form as well as their multi-observable analogues. The new bounds capture both incompatibility and mutually exclusiveness, and are tighter compared with the existing bounds. PMID:27824161

  2. Mutually Exclusive Uncertainty Relations.

    PubMed

    Xiao, Yunlong; Jing, Naihuan

    2016-11-08

    The uncertainty principle is one of the characteristic properties of quantum theory based on incompatibility. Apart from the incompatible relation of quantum states, mutually exclusiveness is another remarkable phenomenon in the information- theoretic foundation of quantum theory. We investigate the role of mutual exclusive physical states in the recent work of stronger uncertainty relations for all incompatible observables by Mccone and Pati and generalize the weighted uncertainty relation to the product form as well as their multi-observable analogues. The new bounds capture both incompatibility and mutually exclusiveness, and are tighter compared with the existing bounds.

  3. Mutually Exclusive Uncertainty Relations

    NASA Astrophysics Data System (ADS)

    Xiao, Yunlong; Jing, Naihuan

    2016-11-01

    The uncertainty principle is one of the characteristic properties of quantum theory based on incompatibility. Apart from the incompatible relation of quantum states, mutually exclusiveness is another remarkable phenomenon in the information- theoretic foundation of quantum theory. We investigate the role of mutual exclusive physical states in the recent work of stronger uncertainty relations for all incompatible observables by Mccone and Pati and generalize the weighted uncertainty relation to the product form as well as their multi-observable analogues. The new bounds capture both incompatibility and mutually exclusiveness, and are tighter compared with the existing bounds.

  4. Mutual Coupling Compensation on Spectral-based DOA Algorithm

    NASA Astrophysics Data System (ADS)

    Sanudin, R.

    2016-11-01

    Direction of arrival (DOA) estimation using isotropic antenna arrays are commonly being implemented without considering the mutual coupling effect in between the array elements. This paper presents an analysis of DOA estimation with mutual coupling compensation using a linear antenna array. Mutual coupling effect is represented by mutual coupling coefficients and taken into account when calculating the array output. The mutual coupling compensation technique exploits a banded mutual coupling matrix to reduce the computational complexity. The banded matrix reflects the relationship between mutual coupling effect and the element spacing in an antenna array. The analysis is being carried out using the Capon algorithm, one of spectral-based DOA algorithms, for estimating the DOA of incoming signals. Computer simulations are performed to show the performance of the mutual coupling compensation technique on DOA estimation. Simulation results show that, in term of estimation resolution, the mutual coupling compensation technique manages to obtain a comparable results compared to the case without mutual coupling consideration. However, the mutual coupling compensation technique produces significant estimation error compared to the case without mutual coupling. The study concludes that the banded matrix of mutual coupling coefficients should be properly designed to improve the performance of mutual coupling compensation technique in DOA estimation.

  5. Evolution of mutualism between species

    SciTech Connect

    Post, W.M.; Travis, C.C.; DeAngelis, D.L.

    1980-01-01

    Recent theoretical work on mutualism, the interaction between species populations that is mutually beneficial, is reviewed. Several ecological facts that should be addressed in the construction of dynamic models for mutualism are examined. Basic terminology is clarified. (PSB)

  6. Weak mutually unbiased bases

    NASA Astrophysics Data System (ADS)

    Shalaby, M.; Vourdas, A.

    2012-02-01

    Quantum systems with variables in { Z}(d) are considered. The properties of lines in the { Z}(d)\\times { Z}(d) phase space of these systems are studied. Weak mutually unbiased bases in these systems are defined as bases for which the overlap of any two vectors in two different bases is equal to d-1/2 or alternatively to one of the d-1/2i, 0 (where di is a divisor of d apart from d, 1). They are designed for the geometry of the { Z}(d)\\times { Z}(d) phase space, in the sense that there is a duality between the weak mutually unbiased bases and the maximal lines through the origin. In the special case of prime d, there are no divisors of d apart from 1, d and the weak mutually unbiased bases are mutually unbiased bases.

  7. Behavioral Ecology: Manipulative Mutualism.

    PubMed

    Hughes, David P

    2015-09-21

    A new study reveals that an apparent mutualism between lycaenid caterpillars and their attendant ants may not be all it seems, as the caterpillars produce secretions that modify the brains and behavior of their attendant ants.

  8. Nematode-bacteria mutualism: Selection within the mutualism supersedes selection outside of the mutualism.

    PubMed

    Morran, Levi T; Penley, McKenna J; Byrd, Victoria S; Meyer, Andrew J; O'Sullivan, Timothy S; Bashey, Farrah; Goodrich-Blair, Heidi; Lively, Curtis M

    2016-03-01

    The coevolution of interacting species can lead to codependent mutualists. Little is known about the effect of selection on partners within verses apart from the association. Here, we determined the effect of selection on bacteria (Xenorhabdus nematophila) both within and apart from its mutualistic partner (a nematode, Steinernema carpocapsae). In nature, the two species cooperatively infect and kill arthropods. We passaged the bacteria either together with (M+), or isolated from (M-), nematodes under two different selection regimes: random selection (S-) and selection for increased virulence against arthropod hosts (S+). We found that the isolated bacteria evolved greater virulence under selection for greater virulence (M-S+) than under random selection (M-S-). In addition, the response to selection in the isolated bacteria (M-S+) caused a breakdown of the mutualism following reintroduction to the nematode. Finally, selection for greater virulence did not alter the evolutionary trajectories of bacteria passaged within the mutualism (M+S+ = M+S-), indicating that selection for the maintenance of the mutualism was stronger than selection for increased virulence. The results show that selection on isolated mutualists can rapidly breakdown beneficial interactions between species, but that selection within a mutualism can supersede external selection, potentially generating codependence over time.

  9. Nematode-Bacteria Mutualism: Selection Within the Mutualism Supersedes Selection Outside of the Mutualism

    PubMed Central

    Morran, Levi T.; Penley, McKenna J.; Byrd, Victoria S.; Meyer, Andrew J.; O’Sullivan, Timothy S.; Bashey, Farrah; Goodrich-Blair, Heidi; Lively, Curtis M.

    2016-01-01

    The coevolution of interacting species can lead to co-dependent mutualists. Little is known about the effect of selection on partners within verses apart from the association. Here, we determined the effect of selection on bacteria (Xenorhabdus nematophila) both within and apart from its mutualistic partner (a nematode, Steinernema carpocapsae). In nature, the two species cooperatively infect and kill arthropods. We passaged the bacteria either together with (M+), or isolated from (M−), nematodes under two different selection regimes: random selection (S−) and selection for increased virulence against arthropod hosts (S+). We found that the isolated bacteria evolved greater virulence under selection for greater virulence (M−S+) than under random selection (M−S−). In addition, the response to selection in the isolated bacteria (M−S+) caused a breakdown of the mutualism following reintroduction to the nematode. Finally, selection for greater virulence did not alter the evolutionary trajectories of bacteria passaged within the mutualism (M+S+ = M+S−), indicating that selection for the maintenance of the mutualism was stronger than selection for increased virulence. The results show that selection on isolated mutualists can rapidly breakdown beneficial interactions between species, but that selection within a mutualism can supersede external selection, potentially generating co-dependence over time. PMID:26867502

  10. Economic contract theory tests models of mutualism.

    PubMed

    Weyl, E Glen; Frederickson, Megan E; Yu, Douglas W; Pierce, Naomi E

    2010-09-07

    Although mutualisms are common in all ecological communities and have played key roles in the diversification of life, our current understanding of the evolution of cooperation applies mostly to social behavior within a species. A central question is whether mutualisms persist because hosts have evolved costly punishment of cheaters. Here, we use the economic theory of employment contracts to formulate and distinguish between two mechanisms that have been proposed to prevent cheating in host-symbiont mutualisms, partner fidelity feedback (PFF) and host sanctions (HS). Under PFF, positive feedback between host fitness and symbiont fitness is sufficient to prevent cheating; in contrast, HS posits the necessity of costly punishment to maintain mutualism. A coevolutionary model of mutualism finds that HS are unlikely to evolve de novo, and published data on legume-rhizobia and yucca-moth mutualisms are consistent with PFF and not with HS. Thus, in systems considered to be textbook cases of HS, we find poor support for the theory that hosts have evolved to punish cheating symbionts; instead, we show that even horizontally transmitted mutualisms can be stabilized via PFF. PFF theory may place previously underappreciated constraints on the evolution of mutualism and explain why punishment is far from ubiquitous in nature.

  11. Economic contract theory tests models of mutualism

    PubMed Central

    Weyl, E. Glen; Frederickson, Megan E.; Yu, Douglas W.; Pierce, Naomi E.

    2010-01-01

    Although mutualisms are common in all ecological communities and have played key roles in the diversification of life, our current understanding of the evolution of cooperation applies mostly to social behavior within a species. A central question is whether mutualisms persist because hosts have evolved costly punishment of cheaters. Here, we use the economic theory of employment contracts to formulate and distinguish between two mechanisms that have been proposed to prevent cheating in host–symbiont mutualisms, partner fidelity feedback (PFF) and host sanctions (HS). Under PFF, positive feedback between host fitness and symbiont fitness is sufficient to prevent cheating; in contrast, HS posits the necessity of costly punishment to maintain mutualism. A coevolutionary model of mutualism finds that HS are unlikely to evolve de novo, and published data on legume–rhizobia and yucca–moth mutualisms are consistent with PFF and not with HS. Thus, in systems considered to be textbook cases of HS, we find poor support for the theory that hosts have evolved to punish cheating symbionts; instead, we show that even horizontally transmitted mutualisms can be stabilized via PFF. PFF theory may place previously underappreciated constraints on the evolution of mutualism and explain why punishment is far from ubiquitous in nature. PMID:20733067

  12. MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs.

    PubMed

    Varga, Zoltán V; Zvara, Agnes; Faragó, Nóra; Kocsis, Gabriella F; Pipicz, Márton; Gáspár, Renáta; Bencsik, Péter; Görbe, Anikó; Csonka, Csaba; Puskás, László G; Thum, Thomas; Csont, Tamás; Ferdinandy, Péter

    2014-07-15

    We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts isolated from male Wistar rats were subjected to 1) time-matched nonischemic perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of reperfusion), 3) preconditioning (3 × 5 min of coronary occlusion) followed by ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 × 10 s of global ischemia-reperfusion at the onset of reperfusion). Infarct size was significantly reduced by both interventions. Of 350 different microRNAs assessed by microarray analysis, 147-160 microRNAs showed detectable expression levels. Compared with microRNA alterations induced by ischemia-reperfusion versus time-matched nonischemic controls, five microRNAs were significantly affected by both pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320, microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212), and nine microRNAs were significantly affected by postconditioning (microRNA-1, microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208, microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected microRNAs was validated by quantitative real-time PCR. By a systematic comparison of the direction of microRNA expression changes in all groups, we identified microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning-like cardioprotective effects (protectomiRs). Transfection of selected protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia-reperfusion showed a significant cytoprotective effect. This is the first demonstration that the ischemia-reperfusion-induced microRNA expression profile is significantly influenced by

  13. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    PubMed Central

    Muraro, Daniele; Mellor, Nathan; Pound, Michael P.; Help, Hanna; Lucas, Mikaël; Chopard, Jérôme; Byrne, Helen M.; Godin, Christophe; Hodgman, T. Charlie; King, John R.; Pridmore, Tony P.; Helariutta, Ykä; Bennett, Malcolm J.; Bishopp, Anthony

    2014-01-01

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot. PMID:24381155

  14. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots.

    PubMed

    Muraro, Daniele; Mellor, Nathan; Pound, Michael P; Help, Hanna; Lucas, Mikaël; Chopard, Jérôme; Byrne, Helen M; Godin, Christophe; Hodgman, T Charlie; King, John R; Pridmore, Tony P; Helariutta, Ykä; Bennett, Malcolm J; Bishopp, Anthony

    2014-01-14

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

  15. Mutually Exclusive, Complementary, or . . .

    ERIC Educational Resources Information Center

    Schloemer, Cathy G.

    2016-01-01

    Whether students are beginning their study of probability or are well into it, distinctions between complementary sets and mutually exclusive sets can be confusing. Cathy Schloemer writes in this article that for years she used typical classroom examples but was not happy with the student engagement or the level of understanding they produced.…

  16. Mutually Exclusive, Complementary, or . . .

    ERIC Educational Resources Information Center

    Schloemer, Cathy G.

    2016-01-01

    Whether students are beginning their study of probability or are well into it, distinctions between complementary sets and mutually exclusive sets can be confusing. Cathy Schloemer writes in this article that for years she used typical classroom examples but was not happy with the student engagement or the level of understanding they produced.…

  17. Mutual Adaptaion in Action

    ERIC Educational Resources Information Center

    Siskin, Leslie Santee

    2016-01-01

    Building on an expanded concept of mutual adaptation, this chapter explores a distinctive and successful aspect of International Baccalaureate's effort to scale up, as they moved to expand their programs and support services in Title I schools. Based on a three-year, mixed-methods study, it offers a case where we see not only local adaptations…

  18. Mutual Adaptaion in Action

    ERIC Educational Resources Information Center

    Siskin, Leslie Santee

    2016-01-01

    Building on an expanded concept of mutual adaptation, this chapter explores a distinctive and successful aspect of International Baccalaureate's effort to scale up, as they moved to expand their programs and support services in Title I schools. Based on a three-year, mixed-methods study, it offers a case where we see not only local adaptations…

  19. Phenological shifts and the fate of mutualisms

    PubMed Central

    Rafferty, Nicole E.; CaraDonna, Paul J.; Bronstein, Judith L.

    2014-01-01

    Climate change is altering the timing of life history events in a wide array of species, many of which are involved in mutualistic interactions. Because many mutualisms can form only if partner species are able to locate each other in time, differential phenological shifts are likely to influence their strength, duration and outcome. At the extreme, climate change-driven shifts in phenology may result in phenological mismatch: the partial or complete loss of temporal overlap of mutualistic species. We have a growing understanding of how, when, and why phenological change can alter one type of mutualism–pollination. However, as we show here, there has been a surprising lack of attention to other types of mutualism. We generate a set of predictions about the characteristics that may predispose mutualisms in general to phenological mismatches. We focus not on the consequences of such mismatches but rather on the likelihood that mismatches will develop. We explore the influence of three key characteristics of mutualism: 1) intimacy, 2) seasonality and duration, and 3) obligacy and specificity. We predict that the following characteristics of mutualism may increase the likelihood of phenological mismatch: 1) a non-symbiotic life history in which co-dispersal is absent; 2) brief, seasonal interactions; and 3) facultative, generalized interactions. We then review the limited available data in light of our a priori predictions and point to mutualisms that are more and less likely to be at risk of becoming phenologically mismatched, emphasizing the need for research on mutualisms other than plant–pollinator interactions. Future studies should explicitly focus on mutualism characteristics to determine whether and how changing phenologies will affect mutualistic interactions. PMID:25883391

  20. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma.

    PubMed

    Sandoval, Juan; Díaz-Lagares, Angel; Salgado, Rocío; Servitje, Octavio; Climent, Fina; Ortiz-Romero, Pablo L; Pérez-Ferriols, Amparo; Garcia-Muret, Maria P; Estrach, Teresa; Garcia, Mar; Nonell, Lara; Esteller, Manel; Pujol, Ramon M; Espinet, Blanca; Gallardo, Fernando

    2015-04-01

    MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.

  1. Mutual help in SETIs

    NASA Astrophysics Data System (ADS)

    Melia, F.; Frisch, D. H.

    1985-06-01

    Techniques to establish communication between earth and extraterrestrial intelligent beings are examined analytically, emphasizing that the success of searches for extraterrestrial intelligence (SETIs) depends on the selection by both sender and receiver of one of a few mutually helpful SETI strategies. An equation for estimating the probability that an SETI will result in the recognition of an ETI signal is developed, and numerical results for various SETI strategies are presented in tables. A minimum approach employing 10 40-m 20-kW dish antennas for a 30-yr SETI in a 2500-light-year disk is proposed.

  2. Pervasive microRNA Duplication in Chelicerates: Insights from the Embryonic microRNA Repertoire of the Spider Parasteatoda tepidariorum

    PubMed Central

    Leite, Daniel J.; Ninova, Maria; Hilbrant, Maarten; Arif, Saad; Griffiths-Jones, Sam; Ronshaugen, Matthew; McGregor, Alistair P.

    2016-01-01

    MicroRNAs are small (∼22 nt) noncoding RNAs that repress translation and therefore regulate the production of proteins from specific target mRNAs. microRNAs have been found to function in diverse aspects of gene regulation within animal development and many other processes. Among invertebrates, both conserved and novel, lineage specific, microRNAs have been extensively studied predominantly in holometabolous insects such as Drosophila melanogaster. However little is known about microRNA repertoires in other arthropod lineages such as the chelicerates. To understand the evolution of microRNAs in this poorly sampled subphylum, we characterized the microRNA repertoire expressed during embryogenesis of the common house spider Parasteatoda tepidariorum. We identified a total of 148 microRNAs in P. tepidariorum representing 66 families. Approximately half of these microRNA families are conserved in other metazoans, while the remainder are specific to this spider. Of the 35 conserved microRNAs families 15 had at least two copies in the P. tepidariorum genome. A BLAST-based approach revealed a similar pattern of duplication in other spiders and a scorpion, but not among other chelicerates and arthropods, with the exception of a horseshoe crab. Among the duplicated microRNAs we found examples of lineage-specific tandem duplications, and the duplication of entire microRNA clusters in three spiders, a scorpion, and in a horseshoe crab. Furthermore, we found that paralogs of many P. tepidariorum microRNA families exhibit arm switching, which suggests that duplication was often followed by sub- or neofunctionalization. Our work shows that understanding the evolution of microRNAs in the chelicerates has great potential to provide insights into the process of microRNA duplication and divergence and the evolution of animal development. PMID:27324919

  3. Defense mutualisms enhance plant diversification

    PubMed Central

    Weber, Marjorie G.; Agrawal, Anurag A.

    2014-01-01

    The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity. PMID:25349406

  4. Defense mutualisms enhance plant diversification.

    PubMed

    Weber, Marjorie G; Agrawal, Anurag A

    2014-11-18

    The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity.

  5. Mutual entropy production in bipartite systems

    NASA Astrophysics Data System (ADS)

    Diana, Giovanni; Esposito, Massimiliano

    2014-04-01

    It was recently shown by Barato et al (2013 Phys. Rev. E 87 042104) that the mutual information at the trajectory level of a bipartite Markovian system is not bounded by the entropy production. In the same way as Gaspard showed (2004 J. Stat. Phys. 117 599) that the entropy production is not directly related to the Shannon entropy at the trajectory level but is in fact equal to its difference from the so-called time-reversed Shannon entropy, we show in this paper that the difference between the mutual information and its time-reversed form is equal to the mutual entropy production (MEP), i.e. the difference between the full entropy production and that of the two marginal processes. Evaluation of the MEP is in general a difficult task due to non-Markovian effects. For bipartite systems, we provide closed expressions in various limiting regimes which we verify by numerical simulations.

  6. Mutual information and spontaneous symmetry breaking

    NASA Astrophysics Data System (ADS)

    Hamma, A.; Giampaolo, S. M.; Illuminati, F.

    2016-01-01

    We show that the metastable, symmetry-breaking ground states of quantum many-body Hamiltonians have vanishing quantum mutual information between macroscopically separated regions and are thus the most classical ones among all possible quantum ground states. This statement is obvious only when the symmetry-breaking ground states are simple product states, e.g., at the factorization point. On the other hand, symmetry-breaking states are in general entangled along the entire ordered phase, and to show that they actually feature the least macroscopic correlations compared to their symmetric superpositions is highly nontrivial. We prove this result in general, by considering the quantum mutual information based on the two-Rényi entanglement entropy and using a locality result stemming from quasiadiabatic continuation. Moreover, in the paradigmatic case of the exactly solvable one-dimensional quantum X Y model, we further verify the general result by considering also the quantum mutual information based on the von Neumann entanglement entropy.

  7. A mutualism-parasitism system modeling host and parasite with mutualism at low density.

    PubMed

    Wang, Yuanshi; Deangelis, Donald L

    2012-04-01

    A mutualism-parasitism system of two species is considered, where mutualism is the dominant interaction when the predators (parasites) are at low density while parasitism is dominant when the predators are at high density. Our aim is to show that mutualism at low density promotes coexistence of the species and leads to high production of the prey (host). The mutualism-parasitism system presented here is a combination of the Lotka-Volterra cooperative model and Lotka-Volterra predator-prey model. By comparing dynamics of this system with those of the Lotka-Volterra predator-prey model, we present the mechanisms by which the mutualism improves the coexistence of the species and production of the prey. Then the parameter space is divided into six regions, which correspond to the four outcomes of mutualism, commensalism, predation/parasitism and neutralism, respectively. When the parameters are varied continuously among the six regions, it is shown that the interaction outcomes of the system transition smoothly among the four outcomes. By comparing the dynamics of the specific system with those of the Lotka-Volterra cooperative model, we show that the parasitism at high density promotes stability of the system. A novel aspect of this paper is the simplicity of the model, which allows rigorous and thorough analysis and transparency of the results.

  8. 26 CFR 1.831-1 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, and...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... mutual), mutual marine insurance companies, and mutual fire insurance companies issuing perpetual... insurance companies (other than life or mutual), mutual marine insurance companies, and mutual fire... marine insurance companies and mutual fire insurance companies exclusively issuing either...

  9. Brain activity: connectivity, sparsity, and mutual information.

    PubMed

    Cassidy, Ben; Rae, Caroline; Solo, Victor

    2015-04-01

    We develop a new approach to functional brain connectivity analysis, which deals with four fundamental aspects of connectivity not previously jointly treated. These are: temporal correlation, spurious spatial correlation, sparsity, and network construction using trajectory (as opposed to marginal) Mutual Information. We call the new method Sparse Conditional Trajectory Mutual Information (SCoTMI). We demonstrate SCoTMI on simulated and real fMRI data, showing that SCoTMI gives more accurate and more repeatable detection of network links than competing network estimation methods.

  10. MicroRNAs: Clinical Relevance in Colorectal Cancer.

    PubMed

    Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui

    2015-11-25

    Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer.

  11. Understanding the coevolutionary dynamics of mutualism with population genomics.

    PubMed

    Yoder, Jeremy B

    2016-10-01

    Decades of research on the evolution of mutualism has generated a wealth of possible ways whereby mutually beneficial interactions between species persist in spite of the apparent advantages to individuals that accept the benefits of mutualism without reciprocating - but identifying how any particular empirical system is stabilized against cheating remains challenging. Different hypothesized models of mutualism stability predict different forms of coevolutionary selection, and emerging high-throughput sequencing methods allow examination of the selective histories of mutualism genes and, thereby, the form of selection acting on those genes. Here, I review the evolutionary theory of mutualism stability and identify how differing models make contrasting predictions for the population genomic diversity and geographic differentiation of mutualism-related genes. As an example of the possibilities offered by genomic data, I analyze genes with roles in the symbiosis of Medicago truncatula and nitrogen-fixing rhizobial bacteria, the first classic mutualism in which extensive genomic resources have been developed for both partners. Medicago truncatula symbiosis genes, as a group, differ from the rest of the genome, but they vary in the form of selection indicated by their diversity and differentiation - some show signs of selection expected from roles in sanctioning noncooperative symbionts, while others show evidence of balancing selection expected from coevolution with symbiont signaling factors. I then assess the current state of development for similar resources in other mutualistic interactions and look ahead to identify ways in which modern sequencing technology can best inform our understanding of mutualists and mutualism.

  12. Mutually unbiased bases and generalized Bell states

    SciTech Connect

    Klimov, Andrei B.; Sych, Denis; Sanchez-Soto, Luis L.; Leuchs, Gerd

    2009-05-15

    We employ a straightforward relation between mutually unbiased and Bell bases to extend the latter in terms of a direct construction for the former. We analyze in detail the properties of these generalized Bell states, showing that they constitute an appropriate tool for testing entanglement in bipartite multiqudit systems.

  13. microRNA Profiling of Amniotic Fluid: Evidence of Synergy of microRNAs in Fetal Development.

    PubMed

    Sun, Tingting; Li, Weiyun; Li, Tianpeng; Ling, Shucai

    2016-01-01

    Amniotic fluid (AF) continuously exchanges molecules with the fetus, playing critical roles in fetal development especially via its complex components. Among these components, microRNAs are thought to be transferred between cells loaded in microvesicles. However, the functions of AF microRNAs remain unknown. To date, few studies have examined microRNAs in amniotic fluid. In this study, we employed miRCURY Locked Nucleotide Acid arrays to profile the dynamic expression of microRNAs in AF from mice on embryonic days E13, E15, and E17. At these times, 233 microRNAs were differentially expressed (p< 0.01), accounting for 23% of the total Mus musculus microRNAs. These differentially-expressed microRNAs were divided into two distinct groups based on their expression patterns. Gene ontology analysis showed that the intersectional target genes of these differentially-expressed microRNAs were mainly distributed in synapse, synaptosome, cell projection, and cytoskeleton. Pathway analysis revealed that the target genes of the two groups of microRNAs were synergistically enriched in axon guidance, focal adhesion, and MAPK signaling pathways. MicroRNA-mRNA network analysis and gene- mapping showed that these microRNAs synergistically regulated cell motility, cell proliferation and differentiation, and especially the axon guidance process. Cancer pathways associated with growth and proliferation were also enriched in AF. Taken together, the results of this study are the first to show the functions of microRNAs in AF during fetal development, providing novel insights into interpreting the roles of AF microRNAs in fetal development.

  14. Estimating mutual information

    NASA Astrophysics Data System (ADS)

    Kraskov, Alexander; Stögbauer, Harald; Grassberger, Peter

    2004-06-01

    We present two classes of improved estimators for mutual information M(X,Y) , from samples of random points distributed according to some joint probability density μ(x,y) . In contrast to conventional estimators based on binnings, they are based on entropy estimates from k -nearest neighbor distances. This means that they are data efficient (with k=1 we resolve structures down to the smallest possible scales), adaptive (the resolution is higher where data are more numerous), and have minimal bias. Indeed, the bias of the underlying entropy estimates is mainly due to nonuniformity of the density at the smallest resolved scale, giving typically systematic errors which scale as functions of k/N for N points. Numerically, we find that both families become exact for independent distributions, i.e. the estimator M̂ (X,Y) vanishes (up to statistical fluctuations) if μ(x,y)=μ(x)μ(y) . This holds for all tested marginal distributions and for all dimensions of x and y . In addition, we give estimators for redundancies between more than two random variables. We compare our algorithms in detail with existing algorithms. Finally, we demonstrate the usefulness of our estimators for assessing the actual independence of components obtained from independent component analysis (ICA), for improving ICA, and for estimating the reliability of blind source separation.

  15. [Biological mutualism, concepts and models].

    PubMed

    Perru, Olivier

    2011-01-01

    Mutualism is a biological association for a mutual benefit between two different species. In this paper, firstly, we examine the history and signification of mutualism in relation to symbiosis. Then, we consider the link between concepts and models of mutualism. Models of mutualism depend on different concepts we use: If mutualism is situated at populations' level, it will be expressed by Lotka-Volterra models, concerning exclusively populations' size. If mutualism is considered as a resources' exchange or a biological market increasing the fitness of these organisms, it will be described at an individual level by a cost-benefit model. Our analysis will be limited to the history and epistemology of Lotka-Volterra models and we hypothesize that these models are adapted at first to translate dynamic evolutions of mutualism. They render stability or variations of size and assume that there are clear distinctions and a state of equilibrium between populations of different species. Italian mathematician Vito Volterra demonstrated that biological associations consist in a constant relation between some species. In 1931 and 1935, Volterra described the general form of antagonistic or mutualistic biological associations by the same differential equations. We recognize that these equations have been more used to model competition or prey-predator interactions, but a simple sign change allows describing mutualism. The epistemological problem is the following: Volterra's equations help us to conceptualize a global phenomenon. However, mutualistic interactions may have stronger effects away from equilibrium and these effects may be better understood at individual level. We conclude that, between 1985 and 2000, some researchers carried on working and converting Lotka-Volterra models but this description appeared as insufficient. So, other researchers adopted an economical viewpoint, considering mutualism as a biological market.

  16. MicroRNA fingerprints during human megakaryocytopoiesis.

    PubMed

    Garzon, Ramiro; Pichiorri, Flavia; Palumbo, Tiziana; Iuliano, Rodolfo; Cimmino, Amelia; Aqeilan, Rami; Volinia, Stefano; Bhatt, Darshna; Alder, Hansjuerg; Marcucci, Guido; Calin, George A; Liu, Chang-Gong; Bloomfield, Clara D; Andreeff, Michael; Croce, Carlo M

    2006-03-28

    microRNAs are a highly conserved class of noncoding RNAs with important regulatory functions in proliferation, apoptosis, development, and differentiation. To discover novel regulatory pathways during megakaryocytic differentiation, we performed microRNA expression profiling of in vitro-differentiated megakaryocytes derived from CD34(+) hematopoietic progenitors. The main finding was down-regulation of miR-10a, miR-126, miR-106, miR-10b, miR-17 and miR-20. Hypothetically, the down-regulation of microRNAs unblocks target genes involved in differentiation. We confirmed in vitro and in vivo that miR-130a targets the transcription factor MAFB, which is involved in the activation of the GPIIB promoter, a key protein for platelet physiology. In addition, we found that miR-10a expression in differentiated megakaryocytes is inverse to that of HOXA1, and we showed that HOXA1 is a direct target of miR-10a. Finally, we compared the microRNA expression of megakaryoblastic leukemic cell lines with that of in vitro differentiated megakaryocytes and CD34(+) progenitors. This analysis revealed up-regulation of miR-101, miR-126, miR-99a, miR-135, and miR-20. Our data delineate the expression of microRNAs during megakaryocytopoiesis and suggest a regulatory role of microRNAs in this process by targeting megakaryocytic transcription factors.

  17. GENERAL: Mutual Information and Relative Entropy of Sequential Effect Algebras

    NASA Astrophysics Data System (ADS)

    Wang, Jia-Mei; Wu, Jun-De; Cho, Minhyung

    2010-08-01

    In this paper, we introduce and investigate the mutual information and relative entropy on the sequential effect algebra, we also give a comparison of these mutual information and relative entropy with the classical ones by the venn diagrams. Finally, a nice example shows that the entropies of sequential effect algebra depend extremely on the order of its sequential product.

  18. Clusters of microRNAs emerge by new hairpins in existing transcripts.

    PubMed

    Marco, Antonio; Ninova, Maria; Ronshaugen, Matthew; Griffiths-Jones, Sam

    2013-09-01

    Genetic linkage may result in the expression of multiple products from a polycistronic transcript, under the control of a single promoter. In animals, protein-coding polycistronic transcripts are rare. However, microRNAs are frequently clustered in the genomes of animals, and these clusters are often transcribed as a single unit. The evolution of microRNA clusters has been the subject of much speculation, and a selective advantage of clusters of functionally related microRNAs is often proposed. However, the origin of microRNA clusters has not been so far explored. Here, we study the evolution of microRNA clusters in Drosophila melanogaster. We observed that the majority of microRNA clusters arose by the de novo formation of new microRNA-like hairpins in existing microRNA transcripts. Some clusters also emerged by tandem duplication of a single microRNA. Comparative genomics show that these clusters are unlikely to split or undergo rearrangements. We did not find any instances of clusters appearing by rearrangement of pre-existing microRNA genes. We propose a model for microRNA cluster evolution in which selection over one of the microRNAs in the cluster interferes with the evolution of the other linked microRNAs. Our analysis suggests that the study of microRNAs and small RNAs must consider linkage associations.

  19. MicroRNAs in Cholangiopathies

    PubMed Central

    O’Hara, Steven P.; Gradilone, Sergio A.; Masyuk, Tetyana V.; Tabibian, James H.; LaRusso, Nicholas F.

    2014-01-01

    Cholangiocytes, the cells lining bile ducts, comprise a small fraction of the total cellular component of the liver, yet perform the essential role of bile modification and transport of biliary and blood constituents. Cholangiopathies are a diverse group of biliary disorders with the cholangiocyte as the target cell; the etiopathogenesis of most cholangiopathies remains obscure. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. These small RNAs may not only be involved in the etiopathogenesis of disease, but are showing promise as diagnostic and prognostic tools. In this brief review, we summarize recent work regarding the role of microRNAs in the etiopathogenesis of several cholangiopathies, and discuss their utility as prognostic and diagnostic tools. PMID:25097819

  20. Mutual Help for the Widowed

    ERIC Educational Resources Information Center

    Abrahams, Ruby Banks

    1972-01-01

    The Widowed Service Line, a mutual help program in metropolitan Boston that provided service by telephone, effectively meeting the various problems and needs of differing stages of widowhood, is described. (Author)

  1. Three-Ship Mutual Interference Tests

    DTIC Science & Technology

    1965-11-16

    increase beyond this event; the data before Event 500 do not show these effects. Short duration transmit-receive misalignment as observed aboard GARCIA , is...on BELKNAP and GARCIA have not been noted on McCLOY. ii 10 CONFIDENTIAL CONFIDENTIAL TRACOR, jNC - , S, Aig? Te~oS 3. CORRECTED SEA TEST LOG Complete...frequency band causing mutual influence. In this example, chart #1 shows BELKNAP and GARCIA influencing McCLOY at a higher frequency band. Sanborn

  2. Relevance of MicroRNA200 Family and MicroRNA205 for Epithelial to Mesenchymal Transition and Clinical Outcome in Biliary Tract Cancer Patients

    PubMed Central

    Urbas, Romana; Mayr, Christian; Klieser, Eckhard; Fuereder, Julia; Bach, Doris; Stättner, Stefan; Primavesi, Florian; Jaeger, Tarkan; Stanzer, Stefanie; Ress, Anna Lena; Löffelberger, Magdalena; Wagner, Andrej; Berr, Frieder; Ritter, Markus; Pichler, Martin; Neureiter, Daniel; Kiesslich, Tobias

    2016-01-01

    Extensive stromal interaction is one reason for the dismal outcome of biliary tract cancer (BTC) patients. Epithelial to mesenchymal transition (EMT) is involved in tumor invasion and metastasis and is partly regulated by microRNAs (miRs). This study explores the expression of anti-EMT miR200 family (miR141, −200a/b/c, −429) and miR205 as well as the EMT-related proteins E-cadherin and vimentin in a panel of BTC cell lines and clinical specimens by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry, respectively. MicroRNA expression was correlated to (i) the expression patterns of E-cadherin and vimentin; (ii) clinicopathological characteristics; and (iii) survival data. MicroRNA-200 family and miR205 were expressed in all BTC cells and clinical specimens. E-cadherin and vimentin showed a mutually exclusive expression pattern in both, in vitro and in vivo. Expression of miR200 family members positively correlated with E-cadherin and negatively with vimentin expression in BTC cells and specimens. High expression of miR200 family members (but not miR205) and E-cadherin was associated with longer survival, while low miR200 family and high vimentin expression was a predictor of unfavorable survival. Overall, the current study demonstrates the relevance of the miR200 family in EMT of BTC tumors and suggests these miRs as predictors for positive outcome. PMID:27941621

  3. Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis.

    PubMed

    Wilson, Ross C; Tambe, Akshay; Kidwell, Mary Anne; Noland, Cameron L; Schneider, Catherine P; Doudna, Jennifer A

    2015-02-05

    RNA-mediated gene silencing in human cells requires the accurate generation of ∼22 nt microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and their genome-wide effects on miRNA processing have not been determined. We solved the crystal structure of the human Dicer-TRBP interface, revealing the structural basis of the interaction. Interface residues conserved between TRBP and PACT show that the proteins bind to Dicer in a similar manner and by mutual exclusion. Based on the structure, a catalytically active Dicer that cannot bind TRBP or PACT was designed and introduced into Dicer-deficient mammalian cells, revealing selective defects in guide strand selection. These results demonstrate the role of Dicer-associated RNA binding proteins in maintenance of gene silencing fidelity.

  4. MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase.

    PubMed

    Liu, Zhenyang; Wang, Junyu; Li, Yunjun; Fan, Juan; Chen, Lihua; Xu, Ruxiang

    2017-02-01

    Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.

  5. Mutually unbiased product bases for multiple qudits

    SciTech Connect

    McNulty, Daniel; Pammer, Bogdan; Weigert, Stefan

    2016-03-15

    We investigate the interplay between mutual unbiasedness and product bases for multiple qudits of possibly different dimensions. A product state of such a system is shown to be mutually unbiased to a product basis only if each of its factors is mutually unbiased to all the states which occur in the corresponding factors of the product basis. This result implies both a tight limit on the number of mutually unbiased product bases which the system can support and a complete classification of mutually unbiased product bases for multiple qubits or qutrits. In addition, only maximally entangled states can be mutually unbiased to a maximal set of mutually unbiased product bases.

  6. Observations of Pluto-Charon mutual events

    SciTech Connect

    Blanco, C.; Di Martino, M.; Ferreri, W.; Osservatorio Astronomico, Turin )

    1989-07-01

    As part of the planned 'Pluto-Charon Mutual Eclipse Season Campaign', one mutual event was observed at the ESO Observatory on July 10, 1986 and seven mutual events were observed at the Serra La Nave stellar station of Catania Astrophysical Observatory from April 29 to July 21, 1987. At ESO the measurements were performed at the 61-cm Bochum telescope equipped with a photon-counting system and U, B, V, filters; at Serra La Nave the Cassegrain focus of the 91-cm reflector was equipped with a photon-counting system and B and V filters. The observed light losses and contact times do not show relevant systematic deviations from the predicted ones. An examination of the behavior of the B and V light curves gives slight indications of a different slope of the B and V light loss of the same event for a superior or an inferior event, and shows that the superior events are shallower at wavelengths longer than B. 6 refs.

  7. Sequence comparisons via algorithmic mutual information

    SciTech Connect

    Milosavijevic, A.

    1994-12-31

    One of the main problems in DNA and protein sequence comparisons is to decide whether observed similarity of two sequences should be explained by their relatedness or by mere presence of some shared internal structure, e.g., shared internal tandem repeats. The standard methods that are based on statistics or classical information theory can be used to discover either internal structure or mutual sequence similarity, but cannot take into account both. Consequently, currently used methods for sequence comparison employ {open_quotes}masking{close_quotes} techniques that simply eliminate sequences that exhibit internal repetitive structure prior to sequence comparisons. The {open_quotes}masking{close_quotes} approach precludes discovery of homologous sequences of moderate or low complexity, which abound at both DNA and protein levels. As a solution to this problem, we propose a general method that is based on algorithmic information theory and minimal length encoding. We show that algorithmic mutual information factors out the sequence similarity that is due to shared internal structure and thus enables discovery of truly related sequences. We extend the recently developed algorithmic significance method to show that significance depends exponentially on algorithmic mutual information.

  8. Quantum Conditional Mutual Information, Reconstructed States, and State Redistribution.

    PubMed

    Brandão, Fernando G S L; Harrow, Aram W; Oppenheim, Jonathan; Strelchuk, Sergii

    2015-07-31

    We give two strengthenings of an inequality for the quantum conditional mutual information of a tripartite quantum state recently proved by Fawzi and Renner, connecting it with the ability to reconstruct the state from its bipartite reductions. Namely, we show that the conditional mutual information is an upper bound on the regularized relative entropy distance between the quantum state and its reconstructed version. It is also an upper bound for the measured relative entropy distance of the state to its reconstructed version. The main ingredient of the proof is the fact that the conditional mutual information is the optimal quantum communication rate in the task of state redistribution.

  9. Spatial Mutual Information Based Hyperspectral Band Selection for Classification

    PubMed Central

    2015-01-01

    The amount of information involved in hyperspectral imaging is large. Hyperspectral band selection is a popular method for reducing dimensionality. Several information based measures such as mutual information have been proposed to reduce information redundancy among spectral bands. Unfortunately, mutual information does not take into account the spatial dependency between adjacent pixels in images thus reducing its robustness as a similarity measure. In this paper, we propose a new band selection method based on spatial mutual information. As validation criteria, a supervised classification method using support vector machine (SVM) is used. Experimental results of the classification of hyperspectral datasets show that the proposed method can achieve more accurate results. PMID:25918742

  10. Nanopore-based detection of circulating microRNAs in lung cancer patients

    NASA Astrophysics Data System (ADS)

    Wang, Yong; Zheng, Dali; Tan, Qiulin; Wang, Michael X.; Gu, Li-Qun

    2011-10-01

    MicroRNAs are short RNA molecules that regulate gene expression, and have been investigated as potential biomarkers because their expression levels are correlated with various diseases. However, detecting microRNAs in the bloodstream remains difficult because current methods are not sufficiently selective or sensitive. Here, we show that a nanopore sensor based on the α-haemolysin protein can selectively detect microRNAs at the single molecular level in plasma samples from lung cancer patients without the need for labels or amplification of the microRNA. The sensor, which uses a programmable oligonucleotide probe to generate a target-specific signature signal, can quantify subpicomolar levels of cancer-associated microRNAs and can distinguish single-nucleotide differences between microRNA family members. This approach is potentially useful for quantitative microRNA detection, the discovery of disease markers and non-invasive early diagnosis of cancer.

  11. Mutual Respect and Civic Education

    ERIC Educational Resources Information Center

    Bird, Colin

    2010-01-01

    Contemporary theories of civic education frequently appeal to an ideal of mutual respect in the context of ethical, ethical and religious disagreement. This paper critically examines two recently popular criticisms of this ideal. The first, coming from a postmodern direction, charges that the ideal is hypocritical in its effort to be maximally…

  12. Hospital mutual aid evacuation plan.

    PubMed

    Phillips, R

    1997-02-01

    Health care facilities need to be prepared for disasters such as floods, tornadoes and earthquakes. Rochester, NY, and its surrounding communities devised a hospital mutual aid evacuation plan in the event a disaster occurs and also to comply with the Joint Commission. This document discusses the plan's development process and also provides the end result.

  13. Mutual Respect and Civic Education

    ERIC Educational Resources Information Center

    Bird, Colin

    2010-01-01

    Contemporary theories of civic education frequently appeal to an ideal of mutual respect in the context of ethical, ethical and religious disagreement. This paper critically examines two recently popular criticisms of this ideal. The first, coming from a postmodern direction, charges that the ideal is hypocritical in its effort to be maximally…

  14. Herbivory eliminates fitness costs of mutualism exploiters.

    PubMed

    Simonsen, Anna K; Stinchcombe, John R

    2014-04-01

    A common empirical observation in mutualistic interactions is the persistence of variation in partner quality and, in particular, the persistence of exploitative phenotypes. For mutualisms between hosts and symbionts, most mutualism theory assumes that exploiters always impose fitness costs on their host. We exposed legume hosts to mutualistic (nitrogen-fixing) and exploitative (non-nitrogen-fixing) symbiotic rhizobia in field conditions, and manipulated the presence or absence of insect herbivory to determine if the costly fitness effects of exploitative rhizobia are context-dependent. Exploitative rhizobia predictably reduced host fitness when herbivores were excluded. However, insects caused greater damage on hosts associating with mutualistic rhizobia, as a consequence of feeding preferences related to leaf nitrogen content, resulting in the elimination of fitness costs imposed on hosts by exploitative rhizobia. Our experiment shows that herbivory is potentially an important factor in influencing the evolutionary dynamic between legumes and rhizobia. Partner choice and host sanctioning are theoretically predicted to stabilize mutualisms by reducing the frequency of exploitative symbionts. We argue that herbivore pressure may actually weaken selection on choice and sanction mechanisms, thus providing one explanation of why host-based discrimination mechanisms may not be completely effective in eliminating nonbeneficial partners.

  15. MicroRNA biomarker identification for pediatric acute myeloid leukemia based on a novel bioinformatics model.

    PubMed

    Yan, Wenying; Xu, Lihua; Sun, Zhandong; Lin, Yuxin; Zhang, Wenyu; Chen, Jiajia; Hu, Shaoyan; Shen, Bairong

    2015-09-22

    Acute myeloid leukemia (AML) in children is a complex and heterogeneous disease. The identification of reliable and stable molecular biomarkers for diagnosis, especially early diagnosis, remains a significant therapeutic challenge. Aberrant microRNA expression could be used for cancer diagnosis and treatment selection. Here, we describe a novel bioinformatics model for the prediction of microRNA biomarkers for the diagnosis of paediatric AML based on computational functional analysis of the microRNA regulatory network substructure. microRNA-196b, microRNA-155 and microRNA-25 were identified as putative diagnostic biomarkers for pediatric AML. Further systematic analysis confirmed the association of the predicted microRNAs with the leukemogenesis of AML. In vitro q-PCR experiments showed that microRNA-155 is significantly overexpressed in children with AML and microRNA-196b is significantly overexpressed in subgroups M4-M5 of the French-American-British classification system. These results suggest that microRNA-155 is a potential diagnostic biomarker for all subgroups of paediatric AML, whereas microRNA-196b is specific for subgroups M4-M5.

  16. Mutual impedance of nonplanar-skew sinusoidal dipoles

    NASA Technical Reports Server (NTRS)

    Richmond, J. H.; Geary, N. H.

    1975-01-01

    The mutual impedance expressions for parallel dipoles in terms of sine-integrals and cosine-integrals have been published by King (1957). The investigation reported provides analogous expressions for nonparallel dipoles. The expressions presented are most useful when the monopoles are close together. The theory of moment methods shows an approach for employing the mutual impedance of filamentary sinusoidal dipoles to calculate the impedance and scattering properties of straight and bent wires with small but finite diameter.

  17. Two Common Bean Genotypes with Contrasting Response to Phosphorus Deficiency Show Variations in the microRNA 399-Mediated PvPHO2 Regulation within the PvPHR1 Signaling Pathway

    PubMed Central

    Ramírez, Mario; Flores-Pacheco, Gerardo; Reyes, José Luis; Álvarez, Ana Luz; Drevon, Jean Jacques; Girard, Lourdes; Hernández, Georgina

    2013-01-01

    Crop production of the important legume, the common bean (Phaseolus vulgaris), is often limited by low phosphorus (P) in the soil. The genotypes, BAT477 and DOR364, of the common bean have contrasting responses to P starvation. Plants from the BAT477 P deficiency tolerant genotype showed higher phosphate content and root biomass as compared to the DOR364 plants under P starvation. The PvPHR1 transcription factor-signaling pathway plays an essential role in the response to P starvation. PvPHO2, a negative regulator of this pathway, encodes an ubiquitin E2 conjugase that promotes degradation of P-responsive proteins and is the target gene of PvmiR399. PvPHO2 is downregulated in BAT477 plants under P deficiency, while such a response is not observed in P-starved DOR364 plants. Five putative PvmiR399 binding sites were identified in the 5′ UTR region in both genotypes. While four sites showed an identical DNA sequence, the fifth (binding site of PvPHO2 one) showed three base changes and higher complementarity scores in DOR364 as compared to BAT477. Modified 5′RACE experiments indicated that PvmiR399 binding and/or processing was affected in DOR364 P-starved plants. We propose that a less efficient cleavage of the PvPHO2 mRNA directed by PvmiR399 would result in a higher PvPHO2-mediated degradation of P-responsive proteins in the DOR364 genotype with decreased P deficiency tolerance. PMID:23591845

  18. Principles of microRNA Regulation Revealed Through Modeling microRNA Expression Quantitative Trait Loci.

    PubMed

    Budach, Stefan; Heinig, Matthias; Marsico, Annalisa

    2016-08-01

    Extensive work has been dedicated to study mechanisms of microRNA-mediated gene regulation. However, the transcriptional regulation of microRNAs themselves is far less well understood, due to difficulties determining the transcription start sites of transient primary transcripts. This challenge can be addressed using expression quantitative trait loci (eQTLs) whose regulatory effects represent a natural source of perturbation of cis-regulatory elements. Here we used previously published cis-microRNA-eQTL data for the human GM12878 cell line, promoter predictions, and other functional annotations to determine the relationship between functional elements and microRNA regulation. We built a logistic regression model that classifies microRNA/SNP pairs into eQTLs or non-eQTLs with 85% accuracy; shows microRNA-eQTL enrichment for microRNA precursors, promoters, enhancers, and transcription factor binding sites; and depletion for repressed chromatin. Interestingly, although there is a large overlap between microRNA eQTLs and messenger RNA eQTLs of host genes, 74% of these shared eQTLs affect microRNA and host expression independently. Considering microRNA-only eQTLs we find a significant enrichment for intronic promoters, validating the existence of alternative promoters for intragenic microRNAs. Finally, in line with the GM12878 cell line derived from B cells, we find genome-wide association (GWA) variants associated to blood-related traits more likely to be microRNA eQTLs than random GWA and non-GWA variants, aiding the interpretation of GWA results. Copyright © 2016 by the Genetics Society of America.

  19. Principles of microRNA Regulation Revealed Through Modeling microRNA Expression Quantitative Trait Loci

    PubMed Central

    Budach, Stefan; Heinig, Matthias; Marsico, Annalisa

    2016-01-01

    Extensive work has been dedicated to study mechanisms of microRNA-mediated gene regulation. However, the transcriptional regulation of microRNAs themselves is far less well understood, due to difficulties determining the transcription start sites of transient primary transcripts. This challenge can be addressed using expression quantitative trait loci (eQTLs) whose regulatory effects represent a natural source of perturbation of cis-regulatory elements. Here we used previously published cis-microRNA-eQTL data for the human GM12878 cell line, promoter predictions, and other functional annotations to determine the relationship between functional elements and microRNA regulation. We built a logistic regression model that classifies microRNA/SNP pairs into eQTLs or non-eQTLs with 85% accuracy; shows microRNA-eQTL enrichment for microRNA precursors, promoters, enhancers, and transcription factor binding sites; and depletion for repressed chromatin. Interestingly, although there is a large overlap between microRNA eQTLs and messenger RNA eQTLs of host genes, 74% of these shared eQTLs affect microRNA and host expression independently. Considering microRNA-only eQTLs we find a significant enrichment for intronic promoters, validating the existence of alternative promoters for intragenic microRNAs. Finally, in line with the GM12878 cell line derived from B cells, we find genome-wide association (GWA) variants associated to blood-related traits more likely to be microRNA eQTLs than random GWA and non-GWA variants, aiding the interpretation of GWA results. PMID:27260304

  20. 26 CFR 1.831-3 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, mutual...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Tax on insurance companies (other than life or... beginning after December 31, 1962. 1.831-3 Section 1.831-3 Internal Revenue INTERNAL REVENUE SERVICE...-3 Tax on insurance companies (other than life or mutual), mutual marine insurance companies, mutual...

  1. Mutuality and the social regulation of neural threat responding.

    PubMed

    Coan, James A; Kasle, Shelley; Jackson, Alice; Schaefer, Hillary S; Davidson, Richard J

    2013-01-01

    Recent studies have shown that the presence of a caring relational partner can attenuate neural responses to threat. Here we report reanalyzed data from Coan, Schaefer, and Davidson ( 2006 ), investigating the role of relational mutuality in the neural response to threat. Mutuality reflects the degree to which couple members show mutual interest in the sharing of internal feelings, thoughts, aspirations, and joys - a vital form of responsiveness in attachment relationships. We predicted that wives who were high (versus low) in perceived mutuality, and who attended the study session with their husbands, would show reduced neural threat reactivity in response to mild electric shocks. We also explored whether this effect would depend on physical contact (hand-holding). As predicted, we observed that higher mutuality scores corresponded with decreased neural threat responding in the right dorsolateral prefrontal cortex and supplementary motor cortex. These effects were independent of hand-holding condition. These findings suggest that higher perceived mutuality corresponds with decreased self-regulatory effort and attenuated preparatory motor activity in response to threat cues, even in the absence of direct physical contact with social resources.

  2. Bio-barcode gel assay for microRNA

    NASA Astrophysics Data System (ADS)

    Lee, Hyojin; Park, Jeong-Eun; Nam, Jwa-Min

    2014-02-01

    MicroRNA has been identified as a potential biomarker because expression level of microRNA is correlated with various cancers. Its detection at low concentrations would be highly beneficial for cancer diagnosis. Here, we develop a new type of a DNA-modified gold nanoparticle-based bio-barcode assay that uses a conventional gel electrophoresis platform and potassium cyanide chemistry and show this assay can detect microRNA at aM levels without enzymatic amplification. It is also shown that single-base-mismatched microRNA can be differentiated from perfectly matched microRNA and the multiplexed detection of various combinations of microRNA sequences is possible with this approach. Finally, differently expressed microRNA levels are selectively detected from cancer cells using the bio-barcode gel assay, and the results are compared with conventional polymerase chain reaction-based results. The method and results shown herein pave the way for practical use of a conventional gel electrophoresis for detecting biomolecules of interest even at aM level without polymerase chain reaction amplification.

  3. Pluto-charon mutual events

    SciTech Connect

    Binzel, R.P. )

    1989-11-01

    Since 1985, planetary astronomers have been working to take advantage of a once-per-century apparent alignment between Pluto and its satellite, Charon, which has allowed mutual occultation and transit events to be observed. There events, which will cease in 1990, have permitted the first precise determinations of their individual radii, densities, and surface compositions. In addition, information on their surface albedo distributions can be obtained.

  4. Mutuality in the provision of Scottish healthcare.

    PubMed

    Howieson, Brian

    2015-11-01

    The backdrop to this article is provided by the Better Health, Better Care Action Plan (Scottish Government, 2007), Section 1 of which is entitled 'Towards a Mutual NHS'. According to Better Health, Better Care (Scottish Government, 2007: 5): 'Mutual organisations are designed to serve their members. They are designed to gather people around a common sense of purpose. They are designed to bring the organisation together in what people often call "co-production."' The aim of this article is to précis the current knowledge of mutuality in the provision of Scottish healthcare. In detail, it will: introduce the 'mutual' organisation; offer a historical perspective of mutuality; suggest why healthcare mutuality is important; and briefly, detail the differences in mutual health-care policy in England and Scotland. It is hoped that this analysis will help researchers and practitioners alike appreciate further the philosophy of mutuality in the provision of Scottish healthcare.

  5. Duplicate Gene Divergence by Changes in MicroRNA Binding Sites in Arabidopsis and Brassica

    PubMed Central

    Wang, Sishuo; Adams, Keith L.

    2015-01-01

    Gene duplication provides large numbers of new genes that can lead to the evolution of new functions. Duplicated genes can diverge by changes in sequences, expression patterns, and functions. MicroRNAs play an important role in the regulation of gene expression in many eukaryotes. After duplication, two paralogs may diverge in their microRNA binding sites, which might impact their expression and function. Little is known about conservation and divergence of microRNA binding sites in duplicated genes in plants. We analyzed microRNA binding sites in duplicated genes in Arabidopsis thaliana and Brassica rapa. We found that duplicates are more often targeted by microRNAs than singletons. The vast majority of duplicated genes in A. thaliana with microRNA binding sites show divergence in those sites between paralogs. Analysis of microRNA binding sites in genes derived from the ancient whole-genome triplication in B. rapa also revealed extensive divergence. Paralog pairs with divergent microRNA binding sites show more divergence in expression patterns compared with paralog pairs with the same microRNA binding sites in Arabidopsis. Close to half of the cases of binding site divergence are caused by microRNAs that are specific to the Arabidopsis genus, indicating evolutionarily recent gain of binding sites after target gene duplication. We also show rapid evolution of microRNA binding sites in a jacalin gene family. Our analyses reveal a dynamic process of changes in microRNA binding sites after gene duplication in Arabidopsis and highlight the role of microRNA regulation in the divergence and contrasting evolutionary fates of duplicated genes. PMID:25644246

  6. Duplicate gene divergence by changes in microRNA binding sites in Arabidopsis and Brassica.

    PubMed

    Wang, Sishuo; Adams, Keith L

    2015-02-02

    Gene duplication provides large numbers of new genes that can lead to the evolution of new functions. Duplicated genes can diverge by changes in sequences, expression patterns, and functions. MicroRNAs play an important role in the regulation of gene expression in many eukaryotes. After duplication, two paralogs may diverge in their microRNA binding sites, which might impact their expression and function. Little is known about conservation and divergence of microRNA binding sites in duplicated genes in plants. We analyzed microRNA binding sites in duplicated genes in Arabidopsis thaliana and Brassica rapa. We found that duplicates are more often targeted by microRNAs than singletons. The vast majority of duplicated genes in A. thaliana with microRNA binding sites show divergence in those sites between paralogs. Analysis of microRNA binding sites in genes derived from the ancient whole-genome triplication in B. rapa also revealed extensive divergence. Paralog pairs with divergent microRNA binding sites show more divergence in expression patterns compared with paralog pairs with the same microRNA binding sites in Arabidopsis. Close to half of the cases of binding site divergence are caused by microRNAs that are specific to the Arabidopsis genus, indicating evolutionarily recent gain of binding sites after target gene duplication. We also show rapid evolution of microRNA binding sites in a jacalin gene family. Our analyses reveal a dynamic process of changes in microRNA binding sites after gene duplication in Arabidopsis and highlight the role of microRNA regulation in the divergence and contrasting evolutionary fates of duplicated genes.

  7. A high-content morphological screen identifies novel microRNAs that regulate neuroblastoma cell differentiation.

    PubMed

    Zhao, Zhenze; Ma, Xiuye; Hsiao, Tzu-Hung; Lin, Gregory; Kosti, Adam; Yu, Xiaojie; Suresh, Uthra; Chen, Yidong; Tomlinson, Gail E; Pertsemlidis, Alexander; Du, Liqin

    2014-05-15

    Neuroblastoma, the most common extracranial solid tumor of childhood, arises from neural crest cell precursors that fail to differentiate. Inducing cell differentiation is an important therapeutic strategy for neuroblastoma. We developed a direct functional high-content screen to identify differentiation-inducing microRNAs, in order to develop microRNA-based differentiation therapy for neuroblastoma. We discovered novel microRNAs, and more strikingly, three microRNA seed families that induce neuroblastoma cell differentiation. In addition, we showed that microRNA seed families were overrepresented in the identified group of fourteen differentiation-inducing microRNAs, suggesting that microRNA seed families are functionally more important in neuroblastoma differentiation than microRNAs with unique sequences. We further investigated the differentiation-inducing function of the microRNA-506-3p/microRNA-124-3p seed family, which was the most potent inducer of differentiation. We showed that the differentiation-inducing function of microRNA-506-3p/microRNA-124-3p is mediated, at least partially, by down-regulating expression of their targets CDK4 and STAT3. We further showed that expression of miR-506-3p, but not miR-124-3p, is dramatically upregulated in differentiated neuroblastoma cells, suggesting the important role of endogenous miR-506-3p in differentiation and tumorigenesis. Overall, our functional screen on microRNAs provided the first comprehensive analysis on the involvements of microRNA species in neuroblastoma cell differentiation and identified novel differentiation-inducing microRNAs. Further investigations are certainly warranted to fully characterize the function of the identified microRNAs in order to eventually benefit neuroblastoma therapy.

  8. A high-content morphological screen identifies novel microRNAs that regulate neuroblastoma cell differentiation

    PubMed Central

    Zhao, Zhenze; Ma, Xiuye; Hsiao, Tzu-Hung; Lin, Gregory; Kosti, Adam; Yu, Xiaojie; Suresh, Uthra; Chen, Yidong; Tomlinson, Gail E.; Pertsemlidis, Alexander; Du, Liqin

    2014-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, arises from neural crest cell precursors that fail to differentiate. Inducing cell differentiation is an important therapeutic strategy for neuroblastoma. We developed a direct functional high-content screen to identify differentiation-inducing microRNAs, in order to develop microRNA-based differentiation therapy for neuroblastoma. We discovered novel microRNAs, and more strikingly, three microRNA seed families that induce neuroblastoma cell differentiation. In addition, we showed that microRNA seed families were overrepresented in the identified group of fourteen differentiation-inducing microRNAs, suggesting that microRNA seed families are functionally more important in neuroblastoma differentiation than microRNAs with unique sequences. We further investigated the differentiation-inducing function of the microRNA-506-3p/microRNA-124-3p seed family, which was the most potent inducer of differentiation. We showed that the differentiation-inducing function of microRNA-506-3p/microRNA-124-3p is mediated, at least partially, by down-regulating expression of their targets CDK4 and STAT3. We further showed that expression of miR-506-3p, but not miR-124-3p, is dramatically upregulated in differentiated neuroblastoma cells, suggesting the important role of endogenous miR-506-3p in differentiation and tumorigenesis. Overall, our functional screen on microRNAs provided the first comprehensive analysis on the involvements of microRNA species in neuroblastoma cell differentiation and identified novel differentiation-inducing microRNAs. Further investigations are certainly warranted to fully characterize the function of the identified microRNAs in order to eventually benefit neuroblastoma therapy. PMID:24811707

  9. MicroRNA evolution, expression, and function during short germband development in Tribolium castaneum.

    PubMed

    Ninova, Maria; Ronshaugen, Matthew; Griffiths-Jones, Sam

    2016-01-01

    MicroRNAs are well-established players in the development of multicellular animals. Most of our understanding of microRNA function in arthropod development comes from studies in Drosophila. Despite their advantages as model systems, the long germband embryogenesis of fruit flies is an evolutionary derived state restricted to several holometabolous insect lineages. MicroRNA evolution and expression across development in animals exhibiting the ancestral and more widespread short germband mode of embryogenesis has not been characterized. We sequenced small RNA libraries of oocytes and successive intervals covering the embryonic development of the short germband model organism, Tribolium castaneum. We analyzed the evolution and temporal expression of the microRNA complement and sequenced libraries of total RNA to investigate the relationships with microRNA target expression. We show microRNA maternal loading and sequence-specific 3' end nontemplate oligoadenylation of maternally deposited microRNAs that is conserved between Tribolium and Drosophila. We further uncover large clusters encoding multiple paralogs from several Tribolium-specific microRNA families expressed during a narrow interval of time immediately after the activation of zygotic transcription. These novel microRNAs, together with several early expressed conserved microRNAs, target a significant number of maternally deposited transcripts. Comparison with Drosophila shows that microRNA-mediated maternal transcript targeting is a conserved process in insects, but the number and sequences of microRNAs involved have diverged. The expression of fast-evolving and species-specific microRNAs in the early blastoderm of T. castaneum is consistent with previous findings in Drosophila and shows that the unique permissiveness for microRNA innovation at this stage is a conserved phenomenon.

  10. Scleral micro-RNA signatures in adult and fetal eyes.

    PubMed

    Metlapally, Ravikanth; Gonzalez, Pedro; Hawthorne, Felicia A; Tran-Viet, Khanh-Nhat; Wildsoet, Christine F; Young, Terri L

    2013-01-01

    In human eyes, ocular enlargement/growth reflects active extracellular matrix remodeling of the outer scleral shell. Micro-RNAs are small non-coding RNAs that regulate gene expression by base pairing with target sequences. They serve as nodes of signaling networks. We hypothesized that the sclera, like most tissues, expresses micro-RNAs, some of which modulate genes regulating ocular growth. In this study, the scleral micro-RNA expression profile of rapidly growing human fetal eyes was compared with that of stable adult donor eyes using high-throughput microarray and quantitative PCR analyses. Scleral samples from normal human fetal (24 wk) and normal adult donor eyes were obtained (n=4 to 6, each group), and RNA extracted. Genome-wide micro-RNA profiling was performed using the Agilent micro-RNA microarray platform. Micro-RNA target predictions were obtained using Microcosm, TargetScan and PicTar algorithms. TaqMan® micro-RNA assays targeting micro-RNAs showing either highest significance, detection, or fold differences, and collagen specificity, were applied to scleral samples from posterior and peripheral ocular regions (n=7, each group). Microarray data were analyzed using R, and quantitative PCR data with 2^-deltaCt methods. Human sclera was found to express micro-RNAs, and comparison of microarray results for adult and fetal samples revealed many to be differentially expressed (p<0.01, min p= 6.5x10(11)). Specifically, fetal sclera showed increased expression of mir-214, let-7c, let-7e, mir-103, mir-107, and mir-98 (1.5 to 4 fold changes, p<0.01). However, no significant regionally specific differences .i.e., posterior vs. peripheral sclera, were observed for either adult or fetal samples. For the first time, micro-RNA expression has been catalogued in human sclera. Some micro-RNAs show age-related differential regulation, higher in the sclera of rapidly growing fetal eyes, consistent with a role in ocular growth regulation. Thus micro-RNAs represent

  11. Scleral Micro-RNA Signatures in Adult and Fetal Eyes

    PubMed Central

    Metlapally, Ravikanth; Gonzalez, Pedro; Hawthorne, Felicia A.; Tran-Viet, Khanh-Nhat; Wildsoet, Christine F.; Young, Terri L.

    2013-01-01

    Introduction In human eyes, ocular enlargement/growth reflects active extracellular matrix remodeling of the outer scleral shell. Micro-RNAs are small non-coding RNAs that regulate gene expression by base pairing with target sequences. They serve as nodes of signaling networks. We hypothesized that the sclera, like most tissues, expresses micro-RNAs, some of which modulate genes regulating ocular growth. In this study, the scleral micro-RNA expression profile of rapidly growing human fetal eyes was compared with that of stable adult donor eyes using high-throughput microarray and quantitative PCR analyses. Methods Scleral samples from normal human fetal (24 wk) and normal adult donor eyes were obtained (n=4 to 6, each group), and RNA extracted. Genome-wide micro-RNA profiling was performed using the Agilent micro-RNA microarray platform. Micro-RNA target predictions were obtained using Microcosm, TargetScan and PicTar algorithms. TaqMan® micro-RNA assays targeting micro-RNAs showing either highest significance, detection, or fold differences, and collagen specificity, were applied to scleral samples from posterior and peripheral ocular regions (n=7, each group). Microarray data were analyzed using R, and quantitative PCR data with 2^-deltaCt methods. Results Human sclera was found to express micro-RNAs, and comparison of microarray results for adult and fetal samples revealed many to be differentially expressed (p<0.01, min p= 6.5x1011). Specifically, fetal sclera showed increased expression of mir-214, let-7c, let-7e, mir-103, mir-107, and mir-98 (1.5 to 4 fold changes, p<0.01). However, no significant regionally specific differences .i.e., posterior vs. peripheral sclera, were observed for either adult or fetal samples. Conclusion For the first time, micro-RNA expression has been catalogued in human sclera. Some micro-RNAs show age-related differential regulation, higher in the sclera of rapidly growing fetal eyes, consistent with a role in ocular growth

  12. 76 FR 36625 - Mutual Holding Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... Office of Thrift Supervision Mutual Holding Company AGENCY: Office of Thrift Supervision (OTS), Treasury... collection. Title of Proposal: Mutual Holding Company. OMB Number: 1550-0072. Form Numbers: MHC-1 (OTS Form... whether the applicant meets the statutory and regulatory criteria to form a mutual holding company...

  13. 76 FR 20458 - Mutual Holding Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-12

    ... Office of Thrift Supervision Mutual Holding Company AGENCY: Office of Thrift Supervision (OTS), Treasury... collection. Title of Proposal: Mutual Holding Company. OMB Number: 1550-0072. Form Numbers: MHC-1 (OTS Form... whether the applicant meets the statutory and regulatory criteria to form a mutual holding company...

  14. Micro-RNA profiling in kidney and bladder cancers.

    PubMed

    Gottardo, Fedra; Liu, Chang Gong; Ferracin, Manuela; Calin, George A; Fassan, Matteo; Bassi, Pierfrancesco; Sevignani, Cinzia; Byrne, Dolores; Negrini, Massimo; Pagano, Francesco; Gomella, Leonard G; Croce, Carlo M; Baffa, Raffaele

    2007-01-01

    Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

  15. Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation

    PubMed Central

    Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

    2015-01-01

    MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details. PMID:26528912

  16. Mutualism exploitation: predatory drosophilid larvae sugar-trap ants and jeopardize facultative ant-plant mutualism.

    PubMed

    Vidal, Mayra C; Sendoya, Sebastian F; Oliveira, Paulo S

    2016-07-01

    An open question in the evolutionary ecology of ant-plant facultative mutualism is how other members of the associated community can affect the interaction to a point where reciprocal benefits are disrupted. While visiting Qualea grandiflora shrubs to collect sugary rewards at extrafloral nectaries, tropical savanna ants deter herbivores and reduce leaf damage. Here we show that larvae of the fly Rhinoleucophenga myrmecophaga, which develop on extrafloral nectaries, lure potentially mutualistic, nectar-feeding ants and prey on them. Foraging ants spend less time on fly-infested foliage. Field experiments showed that predation (or the threat of predation) on ants by fly larvae produces cascading effects through three trophic levels, resulting in fewer protective ants on leaves, increased numbers of chewing herbivores, and greater leaf damage. These results reveal an undocumented mode of mutualism exploitation by an opportunistic predator at a plant-provided food source, jeopardizing ant-derived protection services to the plant. Our study documents a rather unusual case of predation of adult ants by a dipteran species and demonstrates a top-down trophic cascade within a generalized ant-plant mutualism. © 2016 by the Ecological Society of America.

  17. Waveguide mutually pumped phase conjugators.

    PubMed

    James, S W; Youden, K E; Jeffrey, P M; Eason, R W; Chandler, P J; Zhang, L; Townsend, P D

    1993-09-20

    The operation of the bridge mutually pumped phase conjugator is reported in a planar waveguide structure in photorefractive BaTiO(3). The waveguide was fabricated by the technique of ion implantation, using 1.5-MeVH(+) ions at a dose of 10(16) ions/cm(2). An order of magnitude decrease in response time is observed in the waveguide as compared with typical values obtained in bulk crystals, probably as a result of a combination of the optical confinement within the waveguide and possible modification of the charge-transport properties induced by the implantation process.

  18. [Association between hypertension and serum microRNA21 and microRNA133a in ocean seamen].

    PubMed

    Lin, J B; Chai, W L; Zhang, J M; Wang, Y P; Lin, S W; Li, H Y; Wu, S Y

    2016-06-20

    To investigate the prevalence of hypertension in ocean seamen and major influencing factors, as well as the association between hypertension and serum microRNA21 and microRNA133a. Health examination and a questionnaire survey were performed for 780 ocean seamen who underwent physical examination in an international travel healthcare center in Fujian, China from January to June, 2014. TaqMan RT-qPCR was used to measure the serum levels of microRNA21 and microRNA133a in seamen with hypertension. The prevalence of hypertension differed significantly between the ocean seamen with different ages, education levels, marital status, body mass index (BMI) values, drinking frequencies, and numbers of sailing years (P<0.05). The prevalence rate of hypertension in the ocean seamen increased with the increasing drinking frequency (χ(2)=9.02, P<0.05) , decreased with the increase in degree of education (χ(2)=11.578, P<0.05) , and increased with the increase in the number of sailing years (χ(2)=28.06, P<0.05). The hypertensive ocean seamen had significantly higher expression levels of microRNA21 and MicroRNA133a than the healthy ocean seamen (microRNA21: 7.87±5.46 vs 1.03±0.80, P<0.05; MicroRNA133a: 7.45±1.94 vs 4.52±1.15, P<0.05). The multivariate analysis showed that a high level of microRNA21 (OR=1.61, 95% CI: 1.22~2.11) , a high level of microRNA133a (OR=1.52, 95% CI: 1.24~1.87) , drinking (OR=1.64, 95% CI: 1.08~2.50) , overweight based on BMI (OR=1.18, 95%CI: 1.07~1.30) , and many sailing years (OR=2.89, 95% CI: 1.14~7.30) were risk factors for hypertension. The prevention and treatment of hypertension in ocean seamen should be enhanced. Excessive drinking should be controlled, and sailing time should be arranged reasonably. The microRNA21 and microRNA133a may be associated with the development and progression of hypertension in ocean seamen.

  19. Mammalian microRNAs derived from genomic repeats.

    PubMed

    Smalheiser, Neil R; Torvik, Vetle I

    2005-06-01

    In this article, we show that a subset of conventional mammalian microRNAs is derived from LINE-2 transposable elements and other genome repeats. These repeat-derived microRNAs arise from conventional precursor hairpins and are distinct from the rasiRNAs, which appear to be processed from long double-stranded RNA precursors. The insertion of transposable elements into new genomic sites appears to be one of the driving-forces that create new microRNAs during mammalian evolution. Two of the LINE-2-derived microRNAs exhibit perfect complementarity to a large family of mRNA and EST transcripts that contain portions of MIR and other LINE-2 elements in their 3'-untranslated regions.

  20. Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal.

    PubMed

    Zinovyeva, Anna Y; Veksler-Lublinsky, Isana; Vashisht, Ajay A; Wohlschlegel, James A; Ambros, Victor R

    2015-09-22

    MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific Argonaute ALG-1 (Argonaute-like gene) that are antimorphic [alg-1(anti)]. alg-1(anti) mutants have dramatically stronger microRNA-related phenotypes than animals with a complete loss of ALG-1. ALG-1(anti) miRISC (microRNA induced silencing complex) fails to undergo a functional transition from microRNA processing to target repression. To better understand this transition, we characterized the small RNA and protein populations associated with ALG-1(anti) complexes in vivo. We extensively characterized proteins associated with wild-type and mutant ALG-1 and found that the mutant ALG-1(anti) protein fails to interact with numerous miRISC cofactors, including proteins known to be necessary for target repression. In addition, alg-1(anti) mutants dramatically overaccumulated microRNA* (passenger) strands, and immunoprecipitated ALG-1(anti) complexes contained nonstoichiometric yields of mature microRNA and microRNA* strands, with some microRNA* strands present in the ALG-1(anti) Argonaute far in excess of the corresponding mature microRNAs. We show complex and microRNA-specific defects in microRNA strand selection and microRNA* strand disposal. For certain microRNAs (for example mir-58), microRNA guide strand selection by ALG-1(anti) appeared normal, but microRNA* strand release was inefficient. For other microRNAs (such as mir-2), both the microRNA and microRNA* strands were selected as guide by ALG-1(anti), indicating a defect in normal specificity of the strand choice. Our results suggest that wild-type ALG-1 complexes recognize structural features of particular microRNAs in the context of conducting the strand selection and microRNA* ejection steps of miRISC maturation.

  1. Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal

    PubMed Central

    Zinovyeva, Anna Y.; Veksler-Lublinsky, Isana; Vashisht, Ajay A.; Wohlschlegel, James A.; Ambros, Victor R.

    2015-01-01

    MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific Argonaute ALG-1 (Argonaute-like gene) that are antimorphic [alg-1(anti)]. alg-1(anti) mutants have dramatically stronger microRNA-related phenotypes than animals with a complete loss of ALG-1. ALG-1(anti) miRISC (microRNA induced silencing complex) fails to undergo a functional transition from microRNA processing to target repression. To better understand this transition, we characterized the small RNA and protein populations associated with ALG-1(anti) complexes in vivo. We extensively characterized proteins associated with wild-type and mutant ALG-1 and found that the mutant ALG-1(anti) protein fails to interact with numerous miRISC cofactors, including proteins known to be necessary for target repression. In addition, alg-1(anti) mutants dramatically overaccumulated microRNA* (passenger) strands, and immunoprecipitated ALG-1(anti) complexes contained nonstoichiometric yields of mature microRNA and microRNA* strands, with some microRNA* strands present in the ALG-1(anti) Argonaute far in excess of the corresponding mature microRNAs. We show complex and microRNA-specific defects in microRNA strand selection and microRNA* strand disposal. For certain microRNAs (for example mir-58), microRNA guide strand selection by ALG-1(anti) appeared normal, but microRNA* strand release was inefficient. For other microRNAs (such as mir-2), both the microRNA and microRNA* strands were selected as guide by ALG-1(anti), indicating a defect in normal specificity of the strand choice. Our results suggest that wild-type ALG-1 complexes recognize structural features of particular microRNAs in the context of conducting the strand selection and microRNA* ejection steps of miRISC maturation. PMID:26351692

  2. NAViGaTing the micronome--using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs.

    PubMed

    Shirdel, Elize A; Xie, Wing; Mak, Tak W; Jurisica, Igor

    2011-02-25

    MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA:target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA:transcript interactome--referred to as the micronome--to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal--mirDIP (http://ophid.utoronto.ca/mirDIP). mirDIP integrates prediction databases to elucidate accurate microRNA:target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p<0.05), suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p<0.0001), to be more studied (p<0.0002), and to have higher degree in the KEGG cancer pathway (p<0.0001), compared to intra-pathway microRNAs. Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level.

  3. NAViGaTing the Micronome – Using Multiple MicroRNA Prediction Databases to Identify Signalling Pathway-Associated MicroRNAs

    PubMed Central

    Shirdel, Elize A.; Xie, Wing; Mak, Tak W.; Jurisica, Igor

    2011-01-01

    Background MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA:target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA:transcript interactome – referred to as the micronome – to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal — mirDIP (http://ophid.utoronto.ca/mirDIP). Results mirDIP integrates prediction databases to elucidate accurate microRNA:target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p<0.05), suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p<0.0001), to be more studied (p<0.0002), and to have higher degree in the KEGG cancer pathway (p<0.0001), compared to intra-pathway microRNAs. Conclusions Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level. PMID

  4. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  5. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  6. Propagating Resource Constraints Using Mutual Exclusion Reasoning

    NASA Technical Reports Server (NTRS)

    Frank, Jeremy; Sanchez, Romeo; Do, Minh B.; Clancy, Daniel (Technical Monitor)

    2001-01-01

    One of the most recent techniques for propagating resource constraints in Constraint Based scheduling is Energy Constraint. This technique focuses in precedence based scheduling, where precedence relations are taken into account rather than the absolute position of activities. Although, this particular technique proved to be efficient on discrete unary resources, it provides only loose bounds for jobs using discrete multi-capacity resources. In this paper we show how mutual exclusion reasoning can be used to propagate time bounds for activities using discrete resources. We show that our technique based on critical path analysis and mutex reasoning is just as effective on unary resources, and also shows that it is more effective on multi-capacity resources, through both examples and empirical study.

  7. MicroRNAs form triplexes with double stranded DNA at sequence-specific binding sites; a eukaryotic mechanism via which microRNAs could directly alter gene expression

    DOE PAGES

    Paugh, Steven W.; Coss, David R.; Bao, Ju; ...

    2016-02-04

    MicroRNAs are important regulators of gene expression, acting primarily by binding to sequence-specific locations on already transcribed messenger RNAs (mRNA). Recent studies indicate that microRNAs may also play a role in up-regulating mRNA transcription levels, although a definitive mechanism has not been established. Double-helical DNA is capable of forming triple-helical structures through Hoogsteen and reverse Hoogsteen interactions in the major groove of the duplex, and we show physical evidence that microRNAs form triple-helical structures with duplex DNA, and identify microRNA sequences that favor triplex formation. We developed an algorithm (Trident) to search genome-wide for potential triplex-forming sites and show thatmore » several mammalian and non-mammalian genomes are enriched for strong microRNA triplex binding sites. We show that those genes containing sequences favoring microRNA triplex formation are markedly enriched (3.3 fold, p<2.2 x 10-16) for genes whose expression is positively correlated with expression of microRNAs targeting triplex binding sequences. As a result, this work has thus revealed a new mechanism by which microRNAs can interact with gene promoter regions to modify gene transcription.« less

  8. MicroRNAs form triplexes with double stranded DNA at sequence-specific binding sites; a eukaryotic mechanism via which microRNAs could directly alter gene expression

    SciTech Connect

    Paugh, Steven W.; Coss, David R.; Bao, Ju; Laudermilk, Lucas T.; Grace, Christy R.; Ferreira, Antonio M.; Waddell, M. Brett; Ridout, Granger; Naeve, Deanna; Leuze, Michael Rex; LoCascio, Philip F.; Panetta, John C.; Wilkinson, Mark R.; Pui, Ching -Hon; Naeve, Clayton W.; Uberbacher, Edward C.; Bonten, Erik J.; Evans, William E.

    2016-02-04

    MicroRNAs are important regulators of gene expression, acting primarily by binding to sequence-specific locations on already transcribed messenger RNAs (mRNA). Recent studies indicate that microRNAs may also play a role in up-regulating mRNA transcription levels, although a definitive mechanism has not been established. Double-helical DNA is capable of forming triple-helical structures through Hoogsteen and reverse Hoogsteen interactions in the major groove of the duplex, and we show physical evidence that microRNAs form triple-helical structures with duplex DNA, and identify microRNA sequences that favor triplex formation. We developed an algorithm (Trident) to search genome-wide for potential triplex-forming sites and show that several mammalian and non-mammalian genomes are enriched for strong microRNA triplex binding sites. We show that those genes containing sequences favoring microRNA triplex formation are markedly enriched (3.3 fold, p<2.2 x 10-16) for genes whose expression is positively correlated with expression of microRNAs targeting triplex binding sequences. As a result, this work has thus revealed a new mechanism by which microRNAs can interact with gene promoter regions to modify gene transcription.

  9. MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression

    PubMed Central

    Grace, Christy R.; Ferreira, Antonio M.; Waddell, M. Brett; Ridout, Granger; Naeve, Deanna; Leuze, Michael; LoCascio, Philip F.; Panetta, John C.; Wilkinson, Mark R.; Pui, Ching-Hon; Naeve, Clayton W.; Uberbacher, Edward C.; Bonten, Erik J.; Evans, William E.

    2016-01-01

    MicroRNAs are important regulators of gene expression, acting primarily by binding to sequence-specific locations on already transcribed messenger RNAs (mRNA) and typically down-regulating their stability or translation. Recent studies indicate that microRNAs may also play a role in up-regulating mRNA transcription levels, although a definitive mechanism has not been established. Double-helical DNA is capable of forming triple-helical structures through Hoogsteen and reverse Hoogsteen interactions in the major groove of the duplex, and we show physical evidence (i.e., NMR, FRET, SPR) that purine or pyrimidine-rich microRNAs of appropriate length and sequence form triple-helical structures with purine-rich sequences of duplex DNA, and identify microRNA sequences that favor triplex formation. We developed an algorithm (Trident) to search genome-wide for potential triplex-forming sites and show that several mammalian and non-mammalian genomes are enriched for strong microRNA triplex binding sites. We show that those genes containing sequences favoring microRNA triplex formation are markedly enriched (3.3 fold, p<2.2 × 10−16) for genes whose expression is positively correlated with expression of microRNAs targeting triplex binding sequences. This work has thus revealed a new mechanism by which microRNAs could interact with gene promoter regions to modify gene transcription. PMID:26844769

  10. MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression.

    PubMed

    Paugh, Steven W; Coss, David R; Bao, Ju; Laudermilk, Lucas T; Grace, Christy R; Ferreira, Antonio M; Waddell, M Brett; Ridout, Granger; Naeve, Deanna; Leuze, Michael; LoCascio, Philip F; Panetta, John C; Wilkinson, Mark R; Pui, Ching-Hon; Naeve, Clayton W; Uberbacher, Edward C; Bonten, Erik J; Evans, William E

    2016-02-01

    MicroRNAs are important regulators of gene expression, acting primarily by binding to sequence-specific locations on already transcribed messenger RNAs (mRNA) and typically down-regulating their stability or translation. Recent studies indicate that microRNAs may also play a role in up-regulating mRNA transcription levels, although a definitive mechanism has not been established. Double-helical DNA is capable of forming triple-helical structures through Hoogsteen and reverse Hoogsteen interactions in the major groove of the duplex, and we show physical evidence (i.e., NMR, FRET, SPR) that purine or pyrimidine-rich microRNAs of appropriate length and sequence form triple-helical structures with purine-rich sequences of duplex DNA, and identify microRNA sequences that favor triplex formation. We developed an algorithm (Trident) to search genome-wide for potential triplex-forming sites and show that several mammalian and non-mammalian genomes are enriched for strong microRNA triplex binding sites. We show that those genes containing sequences favoring microRNA triplex formation are markedly enriched (3.3 fold, p<2.2 × 10(-16)) for genes whose expression is positively correlated with expression of microRNAs targeting triplex binding sequences. This work has thus revealed a new mechanism by which microRNAs could interact with gene promoter regions to modify gene transcription.

  11. On the mutual information in conformal field theory

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Chen, Lin; Hao, Peng-xiang; Long, Jiang

    2017-06-01

    In this work, we study the universal behaviors in the mutual information of two disjoint spheres in a conformal field theory (CFT). By using the operator product expansion of the spherical twist operator in terms of the conformal family, we show that the large distance expansion of the mutual information can be cast in terms of the conformal blocks. We develop the 1 /n prescription to compute the coefficients before the conformal blocks. For a single conformal family, the leading nonvanishing contribution to the mutual information comes from the bilinear operators. We show that the coefficients of these operators take universal forms and such universal behavior persists in the bilinear operators with derivatives as well. Consequently the first few leading order contributions to the mutual information in CFT take universal forms. To illustrate our framework, we discuss the free scalars and free fermions in various dimensions. For the free scalars, we compute the mutual information to the next-to-leading order and find good agreement with the improved numerical lattice result. For the free fermion, we compute the leading order result, which is of universal form, and find the good match with the numerical study. Our formalism could be applied to any CFT potentially.

  12. Population dynamics and mutualism: Functional responses of benefits and costs

    USGS Publications Warehouse

    Holland, J. Nathaniel; DeAngelis, Donald L.; Bronstein, Judith L.

    2002-01-01

    We develop an approach for studying population dynamics resulting from mutualism by employing functional responses based on density‐dependent benefits and costs. These functional responses express how the population growth rate of a mutualist is modified by the density of its partner. We present several possible dependencies of gross benefits and costs, and hence net effects, to a mutualist as functions of the density of its partner. Net effects to mutualists are likely a monotonically saturating or unimodal function of the density of their partner. We show that fundamental differences in the growth, limitation, and dynamics of a population can occur when net effects to that population change linearly, unimodally, or in a saturating fashion. We use the mutualism between senita cactus and its pollinating seed‐eating moth as an example to show the influence of different benefit and cost functional responses on population dynamics and stability of mutualisms. We investigated two mechanisms that may alter this mutualism's functional responses: distribution of eggs among flowers and fruit abortion. Differences in how benefits and costs vary with density can alter the stability of this mutualism. In particular, fruit abortion may allow for a stable equilibrium where none could otherwise exist.

  13. Show Code.

    PubMed

    Shalev, Daniel

    2017-01-01

    "Let's get one thing straight: there is no such thing as a show code," my attending asserted, pausing for effect. "You either try to resuscitate, or you don't. None of this halfway junk." He spoke so loudly that the two off-service consultants huddled at computers at the end of the unit looked up… We did four rounds of compressions and pushed epinephrine twice. It was not a long code. We did good, strong compressions and coded this man in earnest until the end. Toward the final round, though, as I stepped up to do compressions, my attending looked at me in a deep way. It was a look in between willing me as some object under his command and revealing to me everything that lay within his brash, confident surface but could not be spoken. © 2017 The Hastings Center.

  14. No effect of diffraction on Pluto-Charon mutual events

    NASA Technical Reports Server (NTRS)

    Tholen, D. J.; Hubbard, W. B.

    1988-01-01

    Mulholland and Gustafson (1987) made the interesting suggestion that observations of Pluto-Charon mutual events might show significant dependence on both wavelength and telescope aperture because of diffraction effects. In this letter, observations are presented that show the predicted effects to be absent and demonstrate that the parameters of the system are such that the events can be accurately analyzed with geometrical optics.

  15. Explaining mutualism variation: a new evolutionary paradox?

    PubMed

    Heath, Katy D; Stinchcombe, John R

    2014-02-01

    The paradox of mutualism is typically framed as the persistence of interspecific cooperation, despite the potential advantages of cheating. Thus, mutualism research has tended to focus on stabilizing mechanisms that prevent the invasion of low-quality partners. These mechanisms alone cannot explain the persistence of variation for partner quality observed in nature, leaving a large gap in our understanding of how mutualisms evolve. Studying partner quality variation is necessary for applying genetically explicit models to predict evolution in natural populations, a necessary step for understanding the origins of mutualisms as well as their ongoing dynamics. An evolutionary genetic approach, which is focused on naturally occurring mutualist variation, can potentially synthesize the currently disconnected fields of mutualism evolution and coevolutionary genetics. We outline explanations for the maintenance of genetic variation for mutualism and suggest approaches necessary to address them.

  16. Engineered microRNA therapeutics.

    PubMed

    Gibson, N W

    2014-01-01

    Targeting of microRNAs that are overexpressed or replacement of microRNAs whose expression is lost are two distinct and novel approaches to treat disease(s) driven by microRNA dysregulation. This can be achieved by chemical modification of either a single stranded oligonucleotide called an antimiR or a double stranded nucleic acid molecule termed a microRNA mimic.With hundreds of microRNAs identified and knowledge of their role in disease becoming clearer there is the prospect, over the coming years, to harness engineered microRNA therapeutics to revolutionise the way diseases are treated.Both types of engineered microRNA therapeutics have advanced into clinical development with human proof of concept achieved with an anti-miR targeting miR-122 (one of the most abundant microRNAs in human hepatocytes that is utilised by the hepatitis C virus to enable its function and replication). Rather than targeting individual proteins or enzymes involved in human disease, an opportunity now exists to modulate multiple different proteins/enzymes which act in concert in the progression of disease.

  17. Characteristics of microRNA co-target networks

    NASA Astrophysics Data System (ADS)

    Lee, Chang-Yong

    2011-07-01

    The database of microRNAs and their predicted target genes in humans were used to extract a microRNA co-target network. Based on the finding that more than two miRNAs can target the same gene, we constructed a microRNA co-target network and analyzed it from the perspective of the complex network. We found that a network having a positive assortative mixing can be characterized by small-world and scale-free characteristics which are found in most complex networks. The network was further analyzed by the nearest-neighbor average connectivity, and it was shown that the more assortative a microRNA network is, the wider the range of increasing average connectivity. In particular, an assortative network has a power-law relationship of the average connectivity with a positive exponent. A percolation analysis of the network showed that, although the network is diluted, there is no percolation transition in the network. From these findings, we infer that the microRNAs in the network are clustered together, forming a core group. The same analyses carried out on different species confirmed the robustness of the main results found in the microRNA networks of humans.

  18. MicroRNAs: Clinical Relevance in Colorectal Cancer

    PubMed Central

    Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui

    2015-01-01

    Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer. PMID:26602923

  19. High throughput approaches reveal splicing of primary microRNA transcripts and tissue specific expression of mature microRNAs in Vitis vinifera.

    PubMed

    Mica, Erica; Piccolo, Viviana; Delledonne, Massimo; Ferrarini, Alberto; Pezzotti, Mario; Casati, Cesare; Del Fabbro, Cristian; Valle, Giorgio; Policriti, Alberto; Morgante, Michele; Pesole, Graziano; Pè, M Enrico; Horner, David S

    2009-11-25

    MicroRNAs are short (approximately 21 base) single stranded RNAs that, in plants, are generally coded by specific genes and cleaved specifically from hairpin precursors. MicroRNAs are critical for the regulation of multiple developmental, stress related and other physiological processes in plants. The recent annotation of the genome of the grapevine (Vitis vinifera L.) allowed the identification of many putative conserved microRNA precursors, grouped into multiple gene families. Here we use oligonucleotide arrays to provide the first indication that many of these microRNAs show differential expression patterns between tissues and during the maturation of fruit in the grapevine. Furthermore we demonstrate that whole transcriptome sequencing and deep-sequencing of small RNA fractions can be used both to identify which microRNA precursors are expressed in different tissues and to estimate genomic coordinates and patterns of splicing and alternative splicing for many primary miRNA transcripts. Our results show that many microRNAs are differentially expressed in different tissues and during fruit maturation in the grapevine. Furthermore, the demonstration that whole transcriptome sequencing can be used to identify candidate splicing events and approximate primary microRNA transcript coordinates represents a significant step towards the large-scale elucidation of mechanisms regulating the expression of microRNAs at the transcriptional and post-transcriptional levels.

  20. Developing microRNA therapeutics.

    PubMed

    van Rooij, Eva; Purcell, Angela L; Levin, Arthur A

    2012-02-03

    Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.

  1. 26 CFR 1.831-1 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, and...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... mutual), mutual marine insurance companies, and mutual fire insurance companies issuing perpetual policies. 1.831-1 Section 1.831-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... insurance companies (other than life or mutual), mutual marine insurance companies, and mutual...

  2. 26 CFR 1.831-1 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, and...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... mutual), mutual marine insurance companies, and mutual fire insurance companies issuing perpetual policies. 1.831-1 Section 1.831-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... insurance companies (other than life or mutual), mutual marine insurance companies, and mutual...

  3. [MicroRNAs in neurobiology].

    PubMed

    Kawahara, Yukio

    2008-12-01

    MicroRNAs have emerged as a new regulatory factor of gene expression. They mediate translational repression or degradation of their target mRNAs by RNA interference (RNAi). The expression of each microRNA is tightly regulated in a development- and cell-specific manner by various mechanisms such as blockade of let-7 family expression by Lin-28 or RNA editing. They also act as regulatory switches for development, organogenesis, and cellular differentiation or for controlling distinct functions that are required for the maintenance of each tissue and cell subtypes. The abundant expression of microRNAs as well as the exclusive expression of certain microRNAs in the central nervous system highlights their biological importance at all stages of neural development and in postmitotic and differentiated neurons. Further, some microRNAs, such as miRNA-134, and miRNA-132 are localized and are synthesized in part at synaptic sites in dendrites to regulate synaptic formation and plasticity. In addition to the imparting of basic knowledge about the biogenesis and mechanism of action of microRNAs, this review focuses on the recent advances in microRNA studies in neurobiology, including the expression pattern of microRNAs in the mammalian brain, the role of microRNAs in neural differentiation and maturation, formation and plasticity of synaptic connections, and maintenance of neural function such as the synthesis of the neurotransmitters in selected neurons. Finally, the possible connection between microRNA dysfunction and neurological diseases, and future implications for diagnosis, and treatment of defects in human brain development and neurodegenerative diseases are discussed.

  4. Regulation of pigmentation by microRNAs: MITF-dependent microRNA-211 targets TGF-β receptor 2.

    PubMed

    Dai, Xiaodan; Rao, Chunbao; Li, Huirong; Chen, Yu; Fan, Lilv; Geng, Huiqin; Li, Shuang; Qu, Jia; Hou, Ling

    2015-03-01

    There is growing evidence that microRNAs are important regulators of gene expression in a variety of cell types. Using immortalized cell lines and primary neural crest cell explants, we show that microRNA-211, previously implicated in the regulation of melanoma proliferation and invasiveness, promotes pigmentation in melanoblasts and melanocytes. Expression of this microRNA is regulated by the key melanocyte transcription factor MITF and regulates pigmentation by targeting the TGF-β receptor 2. Transfection with pre-miR-211 precursor molecules in melb-a and melan-a cells leads to a decrease in the expression of TGF-β receptor 2 and reduces the TGF-β signaling-mediated downregulation of two melanogenic enzymes, tyrosinase and tyrosinase-related protein 1. Conversely, downregulation of microRNA-211 using specific microRNA inhibitors has the opposite effects. It appears, therefore, that microRNA-211 serves as a negative regulator of TGF-β signaling which is known to play a important roles in vivo in melanocyte stem cell maintenance and pigmentation.

  5. 26 CFR 1.831-3 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, mutual...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Tax on insurance companies (other than life or... beginning after December 31, 1962. 1.831-3 Section 1.831-3 Internal Revenue INTERNAL REVENUE SERVICE... Companies § 1.831-3 Tax on insurance companies (other than life or mutual), mutual marine...

  6. 26 CFR 1.831-3 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, mutual...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Tax on insurance companies (other than life or... beginning after December 31, 1962. 1.831-3 Section 1.831-3 Internal Revenue INTERNAL REVENUE SERVICE... Companies § 1.831-3 Tax on insurance companies (other than life or mutual), mutual marine...

  7. 26 CFR 1.831-3 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, mutual...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Tax on insurance companies (other than life or... beginning after December 31, 1962. 1.831-3 Section 1.831-3 Internal Revenue INTERNAL REVENUE SERVICE... Companies § 1.831-3 Tax on insurance companies (other than life or mutual), mutual marine insurance...

  8. 26 CFR 1.831-3 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, mutual...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Tax on insurance companies (other than life or... beginning after December 31, 1962. 1.831-3 Section 1.831-3 Internal Revenue INTERNAL REVENUE SERVICE... Companies § 1.831-3 Tax on insurance companies (other than life or mutual), mutual marine insurance...

  9. Occurrence and characteristics of mutual interference between LIDAR scanners

    NASA Astrophysics Data System (ADS)

    Kim, Gunzung; Eom, Jeongsook; Park, Seonghyeon; Park, Yongwan

    2015-05-01

    The LIDAR scanner is at the heart of object detection of the self-driving car. Mutual interference between LIDAR scanners has not been regarded as a problem because the percentage of vehicles equipped with LIDAR scanners was very rare. With the growing number of autonomous vehicle equipped with LIDAR scanner operated close to each other at the same time, the LIDAR scanner may receive laser pulses from other LIDAR scanners. In this paper, three types of experiments and their results are shown, according to the arrangement of two LIDAR scanners. We will show the probability that any LIDAR scanner will interfere mutually by considering spatial and temporal overlaps. It will present some typical mutual interference scenario and report an analysis of the interference mechanism.

  10. Mutual information after a local quench in conformal field theory

    NASA Astrophysics Data System (ADS)

    Asplund, Curtis T.; Bernamonti, Alice

    2014-03-01

    We compute the entanglement entropy and mutual information for two disjoint intervals in two-dimensional conformal field theories as a function of time after a local quench, using the replica trick and boundary conformal field theory. We obtain explicit formulas for the universal contributions, which are leading in the regimes of, for example, close or well-separated intervals of fixed length. The results are largely consistent with the quasiparticle picture, in which entanglement above that present in the ground state is carried by pairs of entangled freely propagating excitations. We also calculate the mutual information for two disjoint intervals in a proposed holographic local quench, whose holographic energy-momentum tensor matches the conformal field theory one. We find that the holographic mutual information shows qualitative differences from the conformal field theory results and we discuss possible interpretations of this.

  11. Empirical study of the tails of mutual fund size

    NASA Astrophysics Data System (ADS)

    Schwarzkopf, Yonathan; Farmer, J. Doyne

    2010-06-01

    The mutual fund industry manages about a quarter of the assets in the U.S. stock market and thus plays an important role in the U.S. economy. The question of how much control is concentrated in the hands of the largest players is best quantitatively discussed in terms of the tail behavior of the mutual fund size distribution. We study the distribution empirically and show that the tail is much better described by a log-normal than a power law, indicating less concentration than, for example, personal income. The results are highly statistically significant and are consistent across fifteen years. This contradicts a recent theory concerning the origin of the power law tails of the trading volume distribution. Based on the analysis in a companion paper, the log-normality is to be expected, and indicates that the distribution of mutual funds remains perpetually out of equilibrium.

  12. Cross Correlation versus Normalized Mutual Information on Image Registration

    NASA Technical Reports Server (NTRS)

    Tan, Bin; Tilton, James C.; Lin, Guoqing

    2016-01-01

    This is the first study to quantitatively assess and compare cross correlation and normalized mutual information methods used to register images in subpixel scale. The study shows that the normalized mutual information method is less sensitive to unaligned edges due to the spectral response differences than is cross correlation. This characteristic makes the normalized image resolution a better candidate for band to band registration. Improved band-to-band registration in the data from satellite-borne instruments will result in improved retrievals of key science measurements such as cloud properties, vegetation, snow and fire.

  13. Synchronization in a Mutualism Ecosystem Induced by Noise Correlation

    NASA Astrophysics Data System (ADS)

    Zhong, Wei-Rong; Shao, Yuan-Zhi; Bie, Meng-Jie; He, Zhen-Hui

    2008-09-01

    Understanding the cause of the synchronization of population evolution is an important issue for ecological improvement. Here we present a Lotka Volterra-type model driven by two correlated environmental noises and show, via theoretical analysis and direct simulation, that noise correlation can induce a synchronization of the mutualists. The time series of mutual species exhibit a chaotic-like fluctuation, which is independent of the noise correlation, however, the chaotic fluctuation of mutual species ratio decreases with the noise correlation. A quantitative parameter defined for characterizing chaotic fluctuation provides a good approach to measure when the complete synchronization happens.

  14. Mutual information-based facial expression recognition

    NASA Astrophysics Data System (ADS)

    Hazar, Mliki; Hammami, Mohamed; Hanêne, Ben-Abdallah

    2013-12-01

    This paper introduces a novel low-computation discriminative regions representation for expression analysis task. The proposed approach relies on interesting studies in psychology which show that most of the descriptive and responsible regions for facial expression are located around some face parts. The contributions of this work lie in the proposition of new approach which supports automatic facial expression recognition based on automatic regions selection. The regions selection step aims to select the descriptive regions responsible or facial expression and was performed using Mutual Information (MI) technique. For facial feature extraction, we have applied Local Binary Patterns Pattern (LBP) on Gradient image to encode salient micro-patterns of facial expressions. Experimental studies have shown that using discriminative regions provide better results than using the whole face regions whilst reducing features vector dimension.

  15. MicroRNAs and essential components of the microRNA processing machinery are not encoded in the genome of the ctenophore Mnemiopsis leidyi.

    PubMed

    Maxwell, Evan K; Ryan, Joseph F; Schnitzler, Christine E; Browne, William E; Baxevanis, Andreas D

    2012-12-20

    MicroRNAs play a vital role in the regulation of gene expression and have been identified in every animal with a sequenced genome examined thus far, except for the placozoan Trichoplax. The genomic repertoires of metazoan microRNAs have become increasingly endorsed as phylogenetic characters and drivers of biological complexity. In this study, we report the first investigation of microRNAs in a species from the phylum Ctenophora. We use short RNA sequencing and the assembled genome of the lobate ctenophore Mnemiopsis leidyi to show that this species appears to lack any recognizable microRNAs, as well as the nuclear proteins Drosha and Pasha, which are critical to canonical microRNA biogenesis. This finding represents the first reported case of a metazoan lacking a Drosha protein. Recent phylogenomic analyses suggest that Mnemiopsis may be the earliest branching metazoan lineage. If this is true, then the origins of canonical microRNA biogenesis and microRNA-mediated gene regulation may postdate the last common metazoan ancestor. Alternatively, canonical microRNA functionality may have been lost independently in the lineages leading to both Mnemiopsis and the placozoan Trichoplax, suggesting that microRNA functionality was not critical until much later in metazoan evolution.

  16. MicroRNAs and essential components of the microRNA processing machinery are not encoded in the genome of the ctenophore Mnemiopsis leidyi

    PubMed Central

    2012-01-01

    Background MicroRNAs play a vital role in the regulation of gene expression and have been identified in every animal with a sequenced genome examined thus far, except for the placozoan Trichoplax. The genomic repertoires of metazoan microRNAs have become increasingly endorsed as phylogenetic characters and drivers of biological complexity. Results In this study, we report the first investigation of microRNAs in a species from the phylum Ctenophora. We use short RNA sequencing and the assembled genome of the lobate ctenophore Mnemiopsis leidyi to show that this species appears to lack any recognizable microRNAs, as well as the nuclear proteins Drosha and Pasha, which are critical to canonical microRNA biogenesis. This finding represents the first reported case of a metazoan lacking a Drosha protein. Conclusions Recent phylogenomic analyses suggest that Mnemiopsis may be the earliest branching metazoan lineage. If this is true, then the origins of canonical microRNA biogenesis and microRNA-mediated gene regulation may postdate the last common metazoan ancestor. Alternatively, canonical microRNA functionality may have been lost independently in the lineages leading to both Mnemiopsis and the placozoan Trichoplax, suggesting that microRNA functionality was not critical until much later in metazoan evolution. PMID:23256903

  17. Plant-based microRNA presences in mice and human sera to breast milk

    USDA-ARS?s Scientific Manuscript database

    Plant foods contain hundreds of thousands of different small RNAs, including microRNAs (miRNAs). A microRNA (miRNA) is a tiny (19-24 nucleotide) piece of RNA that attaches to a specific protein-making mRNA, thus inhibiting protein production. A recent finding shows that a miRNA in rice survives dige...

  18. A Delicate Balance: Maintaining Mutualism to Prevent Disease

    PubMed Central

    Van Tyne, Daria; Gilmore, Michael S.

    2015-01-01

    The intestinal microbial ecosystem is complex, and few of the principles that contribute to homeostasis in health are well understood. Pham et al. (2014) show that a network including the epithelial interleukin-22 receptor protects against infection with the opportunistic pathogen Enterococcus faecalis through promotion of host-microbiota mutualism. PMID:25299326

  19. Physiological Aspects of Communication via Mutual Gaze.

    ERIC Educational Resources Information Center

    Mazur, Allan; And Others

    1980-01-01

    Reports on various social science projects undertaken to investigate nonverbal communication. Findings indicated that mutual gaze influences physiological arousal, an actor can gaze in such a way that he or she manipulates the other person's physiology, and a subject's response to a mutual gaze is a good predictor of dominance or submission in…

  20. Promoting Mutual Help Groups Among Older Persons.

    ERIC Educational Resources Information Center

    Haber, David

    1983-01-01

    Describes several kinds of mutual help groups and two ways to initiate them: (1) through conferences, and (2) through short-term training programs. A substantial need continues for mutual help groups in an era of reduced professional and consumer resources. Research is needed to document their extensiveness, impact and longevity. (JAC)

  1. A parallel genome-wide mRNA and microRNA profiling of the frontal cortex of HIV patients with and without HIV-associated dementia shows the role of axon guidance and downstream pathways in HIV-mediated neurodegeneration

    PubMed Central

    2012-01-01

    Background HIV-associated dementia (HAD) is the most common dementia type in young adults less than 40 years of age. Although the neurotoxins, oxidative/metabolic stress and impaired activity of neurotrophic factors are believed to be underlying reasons for the development of HAD, the genomic basis, which ultimately defines the virus-host interaction and leads to neurologic manifestation of HIV disease is lacking. Therefore, identifying HIV fingerprints on the host gene machinery and its regulation by microRNA holds a great promise and potential for improving our understanding of HAD pathogenesis, its diagnosis and therapy. Results A parallel profiling of mRNA and miRNA of the frontal cortex autopsies from HIV positive patients with and without dementia was performed using Illumina Human-6 BeadChip and Affymetrix version 1.0 miRNA array, respectively. The gene ontology and pathway analysis of the two data sets showed high concordance between miRNA and mRNAs, revealing significant interference with the host axon guidance and its downstream signalling pathways in HAD brains. Moreover, the differentially expressed (DE) miRNAs identified in this study, in particular miR-137, 153 and 218, based on which most correlations were built cumulatively targeted neurodegeneration related pathways, implying their future potential in diagnosis, prognosis and possible therapies for HIV-mediated and possibly other neurodegenerative diseases. Furthermore, this relationship between DE miRNAs and DE mRNAs was also reflected in correlation analysis using Bayesian networks by splitting-averaging strategy (SA-BNs), which revealed 195 statistically significant correlated miRNA-mRNA pairs according to Pearson’s correlation test (P<0.05). Conclusions Our study provides the first evidence on unambiguous support for intrinsic functional relationship between mRNA and miRNA in the context of HIV-mediated neurodegeneration, which shows that neurologic manifestation in HIV patients possibly

  2. Dehydration triggers differential microRNA expression in Xenopus laevis brain.

    PubMed

    Luu, Bryan E; Storey, Kenneth B

    2015-11-15

    African clawed frogs, Xenopus laevis, although primarily aquatic, have a high tolerance for dehydration, being capable of withstanding the loss of up to 32-35% of total water body water. Recent studies have shown that microRNAs play a role in the response to dehydration by the liver, kidney and ventral skin of X. laevis. MicroRNAs act by modulating the expression of mRNA transcripts, thereby affecting diverse biochemical pathways. In this study, 43 microRNAs were assessed in frog brains comparing control and dehydrated (31.2±0.83% of total body water lost) conditions. MicroRNAs of interest were measured using a modified protocol which employs polyadenylation of microRNAs prior to reverse transcription and qPCR. Twelve microRNAs that showed a significant decrease in expression (to 41-77% of control levels) in brains from dehydrated frogs (xla-miR-15a, -150, -181a, -191, -211, -218, -219b, -30c, -30e, -31, -34a, and -34b) were identified. Genomic analysis showed that the sequences of these dehydration-responsive microRNAs were highly conserved as compared with the comparable microRNAs of mice (91-100%). Suppression of these microRNAs implies that translation of the mRNA transcripts under their control could be enhanced in response to dehydration. Bioinformatic analysis using the DIANA miRPath program (v.2.0) predicted the top two KEGG pathways that these microRNAs collectively regulate: 1. Axon guidance, and 2. Long-term potentiation. Previous studies indicated that suppression of these microRNAs promotes neuroprotective pathways by increasing the expression of brain-derived neurotrophic factor and activating anti-apoptotic pathways. This suggests that similar actions may be triggered in X. laevis brains as a protective response to dehydration.

  3. [Maintaining solidarity: is mutuality the solution?].

    PubMed

    Gevers, J K M; Ploem, M C

    2013-01-01

    Solidarity is essentially the willingness to contribute to the community and its demands, which may even involve contributing more than one is expecting to receive. Another principle is mutuality: this refers to a balance between rights and obligations or between mutual obligations. In its advisory document 'The importance of mutuality......solidarity takes work!', The Dutch Council for Public Health and Health Care underlines the importance of ensuring solidarity within the Dutch health care system, e.g. by encouraging patients to take responsibility for their own health, possibly by introducing elements of mutuality. In our contribution, we comment on the Council's advice. Although we fully agree with the overall conclusion that solidarity should be maintained within the system, we do not see how the introduction of increased mutuality will contribute to this goal.

  4. Resource Availability Modulates the Cooperative and Competitive Nature of a Microbial Cross-Feeding Mutualism.

    PubMed

    Hoek, Tim A; Axelrod, Kevin; Biancalani, Tommaso; Yurtsev, Eugene A; Liu, Jinghui; Gore, Jeff

    2016-08-01

    Mutualisms between species play an important role in ecosystem function and stability. However, in some environments, the competitive aspects of an interaction may dominate the mutualistic aspects. Although these transitions could have far-reaching implications, it has been difficult to study the causes and consequences of this mutualistic-competitive transition in experimentally tractable systems. Here, we study a microbial cross-feeding mutualism in which each yeast strain supplies an essential amino acid for its partner strain. We find that, depending upon the amount of freely available amino acid in the environment, this pair of strains can exhibit an obligatory mutualism, facultative mutualism, competition, parasitism, competitive exclusion, or failed mutualism leading to extinction of the population. A simple model capturing the essential features of this interaction explains how resource availability modulates the interaction and predicts that changes in the dynamics of the mutualism in deteriorating environments can provide advance warning that collapse of the mutualism is imminent. We confirm this prediction experimentally by showing that, in the high nutrient competitive regime, the strains rapidly reach a common carrying capacity before slowly reaching the equilibrium ratio between the strains. However, in the low nutrient regime, before collapse of the obligate mutualism, we find that the ratio rapidly reaches its equilibrium and it is the total abundance that is slow to reach equilibrium. Our results provide a general framework for how mutualisms may transition between qualitatively different regimes of interaction in response to changes in nutrient availability in the environment.

  5. Resource Availability Modulates the Cooperative and Competitive Nature of a Microbial Cross-Feeding Mutualism

    PubMed Central

    Hoek, Tim A.; Axelrod, Kevin; Biancalani, Tommaso; Yurtsev, Eugene A.; Gore, Jeff

    2016-01-01

    Mutualisms between species play an important role in ecosystem function and stability. However, in some environments, the competitive aspects of an interaction may dominate the mutualistic aspects. Although these transitions could have far-reaching implications, it has been difficult to study the causes and consequences of this mutualistic–competitive transition in experimentally tractable systems. Here, we study a microbial cross-feeding mutualism in which each yeast strain supplies an essential amino acid for its partner strain. We find that, depending upon the amount of freely available amino acid in the environment, this pair of strains can exhibit an obligatory mutualism, facultative mutualism, competition, parasitism, competitive exclusion, or failed mutualism leading to extinction of the population. A simple model capturing the essential features of this interaction explains how resource availability modulates the interaction and predicts that changes in the dynamics of the mutualism in deteriorating environments can provide advance warning that collapse of the mutualism is imminent. We confirm this prediction experimentally by showing that, in the high nutrient competitive regime, the strains rapidly reach a common carrying capacity before slowly reaching the equilibrium ratio between the strains. However, in the low nutrient regime, before collapse of the obligate mutualism, we find that the ratio rapidly reaches its equilibrium and it is the total abundance that is slow to reach equilibrium. Our results provide a general framework for how mutualisms may transition between qualitatively different regimes of interaction in response to changes in nutrient availability in the environment. PMID:27557335

  6. MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus.

    PubMed

    Bansal, Ajay; Gupta, Vijayalaxmi; Wang, Kenneth

    2016-06-01

    The rapid increase and poor survival of esophageal adenocarcinoma (EAC) have led to significant efforts to promote early detection. Given that the premalignant lesion of Barrett's esophagus (BE) is the major known risk factor for EAC, multiple investigators have studied biomarker signatures that can predict malignant progression of BE to EAC. MicroRNAs, a novel class of gene regulators, are small non-coding RNAs and have been associated with carcinogenesis. MicroRNAs are ideal biomarkers because of their remarkable stability in fixed tissues, a common method for collection of clinical specimens, and in blood either within exosomes or as microRNA-protein complexes. Multiple studies show potential of microRNAs as tissue and blood biomarkers for diagnosis and prognosis of EAC but the results need confirmation in prospective studies. Although head-to-head comparisons are lacking, microRNA panels require less genes than messenger RNA panels for diagnosis of EAC in BE. MicroRNA diagnostic panels will need to be compared for accuracy against global measures of genome instability that were recently shown to be good predictors of progression but require sophisticated analytic techniques. Early studies on blood microRNA panels are promising but have found microRNA markers to be inconsistent among studies. MicroRNA expression in blood is different between various microRNA sub-compartments such as exosomes and microRNA-protein complexes and could affect blood microRNA measurements. Further standardization is needed to yield consistent results. We have summarized the current understanding of the tissue and blood microRNA signatures that may predict the development and progression of EAC.

  7. 12 CFR 575.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Mutual holding company reorganizations. 575.3... COMPANIES § 575.3 Mutual holding company reorganizations. A mutual savings association may reorganize to become a mutual holding company, or join in a mutual holding company reorganization as an...

  8. 12 CFR 239.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Mutual holding company reorganizations. 239.3... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Mutual Holding Companies § 239.3 Mutual holding company reorganizations. (a) A mutual savings association may not reorganize to become...

  9. 12 CFR 575.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 6 2013-01-01 2012-01-01 true Mutual holding company reorganizations. 575.3... COMPANIES § 575.3 Mutual holding company reorganizations. A mutual savings association may reorganize to become a mutual holding company, or join in a mutual holding company reorganization as an...

  10. 12 CFR 239.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Mutual holding company reorganizations. 239.3... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Mutual Holding Companies § 239.3 Mutual holding company reorganizations. (a) A mutual savings association may not reorganize to become...

  11. 12 CFR 575.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Mutual holding company reorganizations. 575.3... COMPANIES § 575.3 Mutual holding company reorganizations. A mutual savings association may reorganize to become a mutual holding company, or join in a mutual holding company reorganization as an...

  12. 12 CFR 575.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Mutual holding company reorganizations. 575.3... COMPANIES § 575.3 Mutual holding company reorganizations. A mutual savings association may reorganize to become a mutual holding company, or join in a mutual holding company reorganization as an...

  13. 12 CFR 239.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Mutual holding company reorganizations. 239.3... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Mutual Holding Companies § 239.3 Mutual holding company reorganizations. (a) A mutual savings association may not reorganize to become...

  14. 12 CFR 575.3 - Mutual holding company reorganizations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Mutual holding company reorganizations. 575.3... COMPANIES § 575.3 Mutual holding company reorganizations. A mutual savings association may reorganize to become a mutual holding company, or join in a mutual holding company reorganization as an...

  15. Expression patterns of micro-RNAs 146a, 181a, and 155 in subacute sclerosing panencephalitis.

    PubMed

    Yiş, Uluç; Tüfekçi, Uğur Kemal; Genç, Şermin; Çarman, Kürşat Bora; Bayram, Erhan; Topçu, Yasemin; Kurul, Semra Hız

    2015-01-01

    Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated virus, showing inflammation, neurodegeneration, and demyelination. Although many factors are emphasized in the pathogenesis of subacute sclerosing panencephalitis, the exact mechanism of neurodegeneration remains unknown. Micro-RNAs are small, noncoding RNAs that regulate gene expression at the posttranscriptional levels. Micro-RNAs are essential for normal immune system development; besides they are also implicated in the pathogenesis of many chronic inflammatory disorders. The aim of this study is to investigate the expression patterns of micro-RNAs 146a, 181a, and 155 in peripheral blood mononuclear cells of patients with subacute sclerosing panencephalitis. We enrolled 39 patients with subacute sclerosing panencephalitis and 41 healthy controls. Quantitative analysis of micro-RNAs 146a, 181a, and 155 were performed using specific stem-loop primers followed by real-time polymerase chain reaction. All of 3 micro-RNAs were upregulated in subacute sclerosing panencephalitis patients. In addition, the level of micro-RNA 155 expression was higher in stage 3 patients. But, micro-RNA 146a and 181a expression levels showed no association or correlation with clinically relevant data. Alteration of peripheral blood mononuclear cell micro-RNAs in subacute sclerosing panencephalitis may shed new light on the pathogenesis of disease and may contribute to the aberrant systemic rise in mRNA levels in subacute sclerosing panencephalitis.

  16. MicroRNA expression profiling using microarrays.

    PubMed

    Love, Cassandra; Dave, Sandeep

    2013-01-01

    MicroRNAs are small noncoding RNAs which are able to regulate gene expression at both the transcriptional and translational levels. There is a growing recognition of the role of microRNAs in nearly every tissue type and cellular process. Thus there is an increasing need for accurate quantitation of microRNA expression in a variety of tissues. Microarrays provide a robust method for the examination of microRNA expression. In this chapter, we describe detailed methods for the use of microarrays to measure microRNA expression and discuss methods for the analysis of microRNA expression data.

  17. Identification of microprocessor-dependent cancer cells allows screening for growth-sustaining micro-RNAs.

    PubMed

    Peric, D; Chvalova, K; Rousselet, G

    2012-04-19

    Micro-RNAs are deregulated in cancer cells, and some are either tumor suppressive or oncogenic. In addition, a link has been established between decreased expression of micro-RNAs and transformation, and several proteins of the RNA interference pathway have been shown to be haploinsufficient tumor suppressors. Oncogenic micro-RNAs (oncomiRs) could represent new therapeutic targets, and their identification is therefore crucial. However, structural and functional redundancy between micro-RNAs hampers approaches relying on individual micro-RNA inhibition. We reasoned that in cancer cells that depend on oncomiRs, impairing the micro-RNA pathway could lead to growth perturbation rather than increased tumorigenesis. Identifying such cells could allow functional analyses of individual micro-RNAs by complementation of the phenotypes observed upon global micro-RNA inhibition. Therefore, we developed episomal vectors coding for small hairpin RNAs targeting either Drosha or DGCR8, the two components of the microprocessor, the nuclear micro-RNA maturation complex. We identified cancer cell lines in which both vectors induced colony growth arrest. We then screened for individual micro-RNAs complementing this growth arrest, and identified miR-19a, miR-19b, miR-20a and miR-27b as major growth-sustaining micro-RNAs. However, the effect of miR-19a and miR-19b was only transient. In addition, embryonic stem cell-derived micro-RNAs with miR-20a seeds were much less efficient than miR-20a in sustaining cancer cell growth, a finding that contrasted with results obtained in stem cells. Finally, we showed that the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10, a shared target of miR-19 and miR-20, was functionally involved in the growth arrest induced by microprocessor inhibition. We conclude that our approach allowed to identify microprocessor-dependent cancer cells, which could be used to screen for growth-sustaining micro-RNAs. This complementation screen

  18. Entropic uncertainty relations and locking: Tight bounds for mutually unbiased bases

    SciTech Connect

    Ballester, Manuel A.; Wehner, Stephanie

    2007-02-15

    We prove tight entropic uncertainty relations for a large number of mutually unbiased measurements. In particular, we show that a bound derived from the result by Maassen and Uffink [Phys. Rev. Lett. 60, 1103 (1988)] for two such measurements can in fact be tight for up to {radical}(d) measurements in mutually unbiased bases. We then show that using more mutually unbiased bases does not always lead to a better locking effect. We prove that the optimal bound for the accessible information using up to {radical}(d) specific mutually unbiased bases is log d/2, which is the same as can be achieved by using only two bases. Our result indicates that merely using mutually unbiased bases is not sufficient to achieve a strong locking effect and we need to look for additional properties.

  19. A meta-analysis: microRNAs' prognostic function in patients with nonsmall cell lung cancer.

    PubMed

    Yu, Na; Zhang, Qingjun; Liu, Qing; Yang, Jiayu; Zhang, Sheng

    2017-08-15

    Accumulating papers have demonstrated that microRNAs play an important role in the progression of lung cancer, mainly as oncogenic and tumor suppressive. Therefore, microRNAs may influence the survival of lung cancer patients. In this meta-analysis, we evaluated the role of microRNAs in affecting the overall survival in nonsmall cell lung cancer (NSCLC) patients, which may provide valuable information for the treatment of nonsmall cell lung cancer. We used keywords to retrieve literatures from online databases PUBMED, EMBASE and Web of Science and included 12 studies into our investigation according to pre-set criteria. Then, we analyzed the data with stata13.1 to evaluate the microRNAs role on the prognosis of NSCLC patients. NSCLC patients with higher microRNAs expression levels tend to show lower overall survival. HR (hazard ratio): 2.49, 95% CI (confidence interval): 1.84-3.37. Besides, both oncogenic and tumor suppressive microRNAs have an evident influence on prognosis with HR values of 2.60 (95% CI: 2.12-3.19) and 0.41 (95% CI: 0.05-0.34), respectively. microRNAs, especially from tissue, have an influence on overall survival of NSCLC patients, which indicates that microRNAs could serve as potential prognostic markers for NSCLC and may provide a treatment strategy for advanced NSCLC patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. Partially penetrant postnatal lethality of an epithelial specific MicroRNA in a mouse knockout.

    PubMed

    Farmer, D'Juan T; Shariat, Nikki; Park, Chong Yon; Liu, Huey Jiin; Mavropoulos, Anastasia; McManus, Michael T

    2013-01-01

    MicroRNAs are small noncoding RNAs thought to have pivotal roles in numerous diseases and developmental processes. However, a growing body of literature indicates that in vivo elimination of these tiny RNAs usually has little to no observable consequence, suggesting functional redundancy with other microRNAs or cellular pathways. We provide an in-depth analysis of miR-205 expression and define miR-205 as an epithelial-specific microRNA, and for the first time show that ablation of this microRNA knockout exhibits partially penetrant lethality in a constitutive mouse knockout model. Given the role of this microRNA in cancer and development, this mouse model will be an incredible reagent to study the function and mechanisms of miR-205 in epithelial tissue development and disease.

  1. A color-mediated mutualism between two arthropod predators.

    PubMed

    Peng, Po; Blamires, Sean J; Agnarsson, Ingi; Lin, Hui-Chen; Tso, I-Min

    2013-01-21

    The nature of interactions between animals varies depending on local selection pressure, trophic status of the participants, and evolutionary circumstances. Body coloration and other visual signals may also affect animal interactions. Game theory posits that if one species provides a "service" in exchange for a "goods," a mutualism may ensue. Mutualisms between two predators are rare because of multiple conflicts of interests (but see [11, 12]). We used a nocturnal system traditionally considered kleptoparasitic to determine whether a mutualism ensues because the body coloration of the kleptoparasite is beneficial to the host. Specifically, we tested whether the silver body of the spider Argyrodes fissifrons (Theridiidae) attracts prey for the larger, duller spider Cyrtophora unicolor (Araneidae), which reciprocates by allowing A. fissifrons access to its web. When A. fissifrons were removed from C. unicolor webs, the webs intercepted fewer prey. Furthermore, covering the silver body parts of A. fissifrons also resulted in a reduction in prey interception by C. unicolor webs. We thus show that a mutualism between two arthropod predators can be mediated by the coloration of one species enhancing the foraging gains of another.

  2. Functional analysis of mutual behavior in laboratory rats (Rattus norvegicus)

    PubMed Central

    Tan, Lavinia; Hackenberg, Timothy D.

    2015-01-01

    Three pairs of rats were trained to synchronize their lever pressing according to a mutual reinforcement contingency, in which alternating lever presses that fell within a 500-ms window were reinforced with food. In Experiment 1, rats worked in adjacent chambers separated by a transparent barrier, and the effects of the mutual reinforcement contingency were compared to those under yoked-control conditions that provided the same rate of food reinforcement but without the temporal coordination response requirement. In Experiment 2, coordinated behavior was compared with and without a barrier, and across different barrier types: transparent, opaque, wire mesh. In Experiment 3, the effects of social familiarity were assessed by switching partners, enabling a comparison of coordinated behavior with familiar and unfamiliar partners. The overall pattern of results shows that the coordinated behavior of two rats was (a) maintained by mutual reinforcement contingencies, (b) unrelated to the type or presence of a barrier separating the rats, and (c) sufficiently flexible to adjust to the presence and behavior of an unfamiliar partner. Taken as a whole, the study illustrates a promising approach to conceptualizing and analyzing behavioral mechanisms of mutual behavior, an important component of an integrated study of social behavior. PMID:26479279

  3. Mycorrhiza: A Common Form of Mutualism.

    ERIC Educational Resources Information Center

    Medve, Richard J.

    1978-01-01

    Mycorrhizae are among the most common examples of mutualism. This article discusses their structure, symbolic relationship, factors affecting formation and applying research. Questions are posed and answers suggested. (MA)

  4. Mycorrhiza: A Common Form of Mutualism.

    ERIC Educational Resources Information Center

    Medve, Richard J.

    1978-01-01

    Mycorrhizae are among the most common examples of mutualism. This article discusses their structure, symbolic relationship, factors affecting formation and applying research. Questions are posed and answers suggested. (MA)

  5. Direction Finding With Mutually Orthogonal Antennas

    DTIC Science & Technology

    2011-03-24

    BIB - 1 ix List of Figures Figure Page 1 - 1 : Mutually...Likelihood Results 50mm Antennas 0.5GHz, with MUTUAL COUPLING Figure C - 79 : α = 1 ° Figure C - 80: α = 10° Figure C - 81: α = 20...146: α = 10° Figure C - 147: α = 20° Figure C - 148: α = 30° Figure C - 149: α = 40° Figure C - 150: α = 50° BIB - 1 BIBLIOGRAPHY [ 1

  6. Economic game theory for mutualism and cooperation.

    PubMed

    Archetti, Marco; Scheuring, István; Hoffman, Moshe; Frederickson, Megan E; Pierce, Naomi E; Yu, Douglas W

    2011-12-01

    We review recent work at the interface of economic game theory and evolutionary biology that provides new insights into the evolution of partner choice, host sanctions, partner fidelity feedback and public goods. (1) The theory of games with asymmetrical information shows that the right incentives allow hosts to screen-out parasites and screen-in mutualists, explaining successful partner choice in the absence of signalling. Applications range from ant-plants to microbiomes. (2) Contract theory distinguishes two longstanding but weakly differentiated explanations of host response to defectors: host sanctions and partner fidelity feedback. Host traits that selectively punish misbehaving symbionts are parsimoniously interpreted as pre-adaptations. Yucca-moth and legume-rhizobia mutualisms are argued to be examples of partner fidelity feedback. (3) The theory of public goods shows that cooperation in multi-player interactions can evolve in the absence of assortment, in one-shot social dilemmas among non-kin. Applications include alarm calls in vertebrates and exoenzymes in microbes. 2011 Blackwell Publishing Ltd/CNRS.

  7. Gene regulation: ancient microRNA target sequences in plants.

    PubMed

    Floyd, Sandra K; Bowman, John L

    2004-04-01

    MicroRNAs are an abundant class of small RNAs that are thought to regulate the expression of protein-coding genes in plants and animals. Here we show that the target sequence of two microRNAs, known to regulate genes in the class-III homeodomain-leucine zipper (HD-Zip) gene family of the flowering plant Arabidopsis, is conserved in homologous sequences from all lineages of land plants, including bryophytes, lycopods, ferns and seed plants. We also find that the messenger RNAs from these genes are cleaved within the same microRNA-binding site in representatives of each land-plant group, as they are in Arabidopsis. Our results indicate not only that microRNAs mediate gene regulation in non-flowering as well as flowering plants, but also that the regulation of this class of plant genes dates back more than 400 million years.

  8. CoGemiR: A comparative genomics microRNA database

    PubMed Central

    Maselli, Vincenza; Di Bernardo, Diego; Banfi, Sandro

    2008-01-01

    Background MicroRNAs are small highly conserved non-coding RNAs which play an important role in regulating gene expression by binding the 3'UTR of target mRNAs. The majority of microRNAs are localized within other transcriptional units (host genes) and are co-expressed with them, which strongly suggests that microRNAs and corresponding host genes use the same promoter and other expression control elements. The remaining fraction of microRNAs is intergenic and is endowed with an independent regulatory region. A number of databases have already been developed to collect information about microRNAs but none of them allow an easy exploration of microRNA genomic organization across evolution. Results CoGemiR is a publicly available microRNA-centered database whose aim is to offer an overview of the genomic organization of microRNAs and of its extent of conservation during evolution in different metazoan species. The database collects information on genomic location, conservation and expression data of both known and newly predicted microRNAs and displays the data by privileging a comparative point of view. The database also includes a microRNA prediction pipeline to annotate microRNAs in recently sequenced genomes. This information is easily accessible via web through a user-friendly query page. The CoGemiR database is available at Conclusion The knowledge of the genomic organization of microRNAs can provide useful information to understand their biology. In order to have a comparative genomics overview of microRNAs genomic organization, we developed CoGemiR. To achieve this goal, we both collected and integrated data from pre-existing databases and generated new ones, such as the identification in several species of a number of previously unannotated microRNAs. For a more effective use of this data, we developed a user-friendly web interface that simply shows how a microRNA genomic context is related in different species. PMID:18837977

  9. Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways.

    PubMed

    Nakao, Tetsushi; Horie, Takahiro; Baba, Osamu; Nishiga, Masataka; Nishino, Tomohiro; Izuhara, Masayasu; Kuwabara, Yasuhide; Nishi, Hitoo; Usami, Shunsuke; Nakazeki, Fumiko; Ide, Yuya; Koyama, Satoshi; Kimura, Masahiro; Sowa, Naoya; Ohno, Satoko; Aoki, Hiroki; Hasagawa, Koji; Sakamoto, Kazuhisa; Minatoya, Kenji; Kimura, Takeshi; Ono, Koh

    2017-09-07

    Abdominal aortic aneurysm (AAA) is an increasingly prevalent and ultimately fatal disease with no effective pharmacological treatment. Because matrix degradation induced by vascular inflammation is the major pathophysiology of AAA, attenuation of this inflammation may improve its outcome. Previous studies suggested that microRNA-33 inhibition and genetic ablation of microRNA-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis. MicroRNA-33a-5p expression in central zone of human AAA was higher than marginal zone. MicroRNA-33 deletion attenuated AAA formation in both mouse models of angiotensin II- and calcium chloride-induced AAA. Reduced macrophage accumulation and monocyte chemotactic protein-1 expression were observed in calcium chloride-induced AAA walls in microRNA-33(-/-) mice. In vitro experiments revealed that peritoneal macrophages from microRNA-33(-/-) mice showed reduced matrix metalloproteinase 9 expression levels via c-Jun N-terminal kinase inactivation. Primary aortic vascular smooth muscle cells from microRNA-33(-/-) mice showed reduced monocyte chemotactic protein-1 expression by p38 mitogen-activated protein kinase attenuation. Both of the inactivation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were possibly because of the increase of ATP-binding cassette transporter A1 that is a well-known target of microRNA-33. Moreover, high-density lipoprotein cholesterol derived from microRNA-33(-/-) mice reduced expression of matrix metalloproteinase 9 in macrophages and monocyte chemotactic protein-1 in vascular smooth muscle cells. Bone marrow transplantation experiments indicated that microRNA-33-deficient bone marrow cells ameliorated AAA formation in wild-type recipients. MicroRNA-33 deficiency in recipient mice was also shown to contribute the inhibition of AAA formation. These data strongly suggest that inhibition of microRNA-33 will be effective as a novel strategy for treating AAA. © 2017

  10. Dicer–TRBP complex formation ensures accurate mammalian microRNA biogenesis

    PubMed Central

    Wilson, Ross C.; Tambe, Akshay; Kidwell, Mary Anne; Noland, Cameron L.; Schneider, Catherine P.; Doudna, Jennifer A.

    2014-01-01

    Summary RNA-mediated gene silencing in human cells requires the accurate generation of ∼22-nucleotide microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and their genome-wide effects on miRNA processing have not been determined. We solved the crystal structure of a human Dicer–TRBP interaction complex comprising two domains of previously unknown structure. Interface residues conserved between TRBP and PACT show that the proteins bind to Dicer in a similar manner and by mutual exclusion. Based on the structure, a catalytically active Dicer that cannot bind TRBP or PACT was designed and introduced into Dicer-deficient mammalian cells, revealing selective defects in guide strand selection. These results demonstrate the role of Dicer-associated RNA binding proteins in maintenance of gene silencing fidelity. PMID:25557550

  11. MicroRNA-1 and microRNA-206 improve differentiation potential of human satellite cells: a novel approach for tissue engineering of skeletal muscle.

    PubMed

    Koning, Merel; Werker, Paul M N; van der Schaft, Daisy W J; Bank, Ruud A; Harmsen, Martin C

    2012-05-01

    Innovative strategies based on regenerative medicine, in particular tissue engineering of skeletal muscle, are promising for treatment of patients with skeletal muscle damage. However, the efficiency of satellite cell differentiation in vitro is suboptimal. MicroRNAs are involved in the regulation of cell proliferation and differentiation. We hypothesized that transient overexpression of microRNA-1 or microRNA-206 enhances the differentiation potential of human satellite cells by downregulation quiescent satellite cell regulators, thereby increasing myogenic regulator factors. To investigate this, we isolated and cultured human satellite cells from muscle biopsies. First, through immunofluorescent analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we showed that in satellite cell cultures, low Pax7 expression is related to high MyoD expression on differentiation, and, subsequently, more extensive sarcomere formation, that is, muscle differentiation, was detected. Second, using qRT-PCR, we showed that microRNA-1 and microRNA-206 are robustly induced in differentiating satellite cells. Finally, a gain-of-function approach was used to investigate microRNA-1 and microRNA-206 potential in human satellite cells to improve differentiation potential. As a proof of concept, this was also investigated in a three-dimensional bioartificial muscle construct. After transfection with microRNA-1, the number of Pax7 expressing cells decreased compared with the microRNA-scrambled control. In differentiated satellite cell cultures transfected with either microRNA-1 or microRNA-206, the number of MyoD expressing cells increased, and α-sarcomeric actin and myosin expression increased compared with microRNA-scrambled control cultures. In addition, in a three-dimensional bioartificial muscle construct, an increase in MyoD expression occurred. Therefore, we conclude that microRNA-1 and microRNA-206 can improve human satellite cell differentiation. It

  12. [MicroRNAs and kidneys].

    PubMed

    Stříteská, Jana; Nekvindová, Jana; Cerný, Vladimír; Palička, Vladimír

    2014-01-01

    MicroRNAs are short non-coding ribonucleic acid molecules that regulate gene expression at the post-transcriptional level thus affecting important physiological as well as pathophysiological processes in the organism, for example cell differentiation, proliferation, apoptosis, and metabolism. They are involved in pathogenesis of many diseases including cancer. Many microRNAs are tissue or organ-specific which implies their possible potential as biomarkers or maybe even therapeutical agents as documented by microRNA research interest rising exponentially during last years. Among all, microRNAs are important also for physiological function of the kidney and they are involved in various renal disorders. Today research is focused mainly on renal and urinary tract carcinogenesis, acute kidney injury, chronic renal diseases (polycystic kidney disease) or renal complications of systemic diseases such as diabetic or hypertension nephropathy and autoimmune kidney injury including acute allograft rejection after kidney transplantation. The review summarizes current information about microRNA effect on kidney development and function and also on the most common kidney diseases.

  13. Female partners of men who use pornography: are honesty and mutual use associated with relationship satisfaction?

    PubMed

    Resch, Marley N; Alderson, Kevin G

    2014-01-01

    The authors discuss findings pertaining to male pornography use and female partners' relationship satisfaction and distress. The authors investigated honesty regarding pornography use and mutual consumption between partners, along with honesty and mutual use as predictors of satisfaction. Female participants (N = 340) in committed relationships completed the Pornography Distress Scale and Couples Satisfaction Index online. Participants reporting more honesty showed higher satisfaction and lower levels of distress, and participants disclosing mutual use showed lower levels of distress, although no differences were reported in satisfaction. Honesty regarding pornography use significantly predicted relationship dissatisfaction. Directions for future research and counseling implications are discussed.

  14. MicroRNA Regulation of Lipid Metabolism

    PubMed Central

    Flowers, Elena; Froelicher, Erika Sivarajan; Aouizerat, Bradley E.

    2012-01-01

    MicroRNA are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis. PMID:22607769

  15. The copper microRNAs.

    PubMed

    Pilon, Marinus

    2017-02-01

    1030 I. 1030 II. 1030 III. 1031 IV. 1031 V. 1032 VI. 1033 VII. 1034 VIII. 1034 1034 References 1034 SUMMARY: Copper (Cu) microRNAs are upregulated by Cu deficiency and mediate the post-transcriptional downregulation of transcripts that encode Cu proteins, suggesting a role directly related to Cu. However, expression and phenotypic analyses of copper microRNA mutants and over-expressors have suggested roles mainly in tolerance to abiotic stresses. To reconcile available data, a model is proposed which emphasizes the mobile nature of copper microRNA molecules in the regulation of Cu homeostasis. It is proposed that the Cu-microRNA regulatory circuits are further co-opted by plants to regulate both beneficial and pathogenic interactions with microbes. Further exploration of Cu-microRNA functions that account for the cell-to-cell mobility should give novel insight into plant microbe interactions and the integration of micronutrition and development.

  16. MicroRNA-9

    PubMed Central

    Yuva-Aydemir, Yeliz; Simkin, Alfred; Gascon, Eduardo

    2011-01-01

    The functional significance of microRNA-9 (miR-9) during evolution is evidenced by its conservation at the nucleotide level from flies to humans but not its diverse expression patterns. Recent studies in several model systems reveal that miR-9 can regulate neurogenesis through its actions in neural or non-neural cell lineages. In vertebrates, miR-9 exerts diverse cell-autonomous effects on the proliferation, migration and differentiation of neural progenitor cells by modulating different mRNA targets. In some developmental contexts, miR-9 suppresses apoptosis and is misregulated in several types of cancer cells, influencing proliferation or metastasis formation. Moreover, downregulation of miR-9 in postmitotic neurons is also implicated in some neurodegenerative diseases. Thus, miR-9 is emerging as an important regulator in development and disease through its ability to modulate different targets in a manner dependent on the developmental stage and the cellular context. PMID:21697652

  17. 75 FR 77048 - Mutual Savings Association Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-10

    ... Office of Thrift Supervision Mutual Savings Association Advisory Committee AGENCY: Department of the... Thrift Supervision has determined that the renewal of the ] Charter of the OTS Mutual Savings Association... facing mutual savings associations. DATES: The Charter of the OTS Mutual Savings Association Advisory...

  18. 12 CFR 544.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Federal mutual savings association bylaws. 544... MUTUAL SAVINGS ASSOCIATIONS-CHARTER AND BYLAWS Bylaws § 544.5 Federal mutual savings association bylaws. (a) General. A Federal mutual savings association shall operate under bylaws that contain provisions...

  19. Integrating plant carbon dynamics with mutualism ecology.

    PubMed

    Pringle, Elizabeth G

    2016-04-01

    Plants reward microbial and animal mutualists with carbohydrates to obtain nutrients, defense, pollination, and dispersal. Under a fixed carbon budget, plants must allocate carbon to their mutualists at the expense of allocation to growth, reproduction, or storage. Such carbon trade-offs are indirectly expressed when a plant exhibits reduced growth or fecundity in the presence of its mutualist. Because carbon regulates the costs of all plant mutualisms, carbon dynamics are a common platform for integrating these costs in the face of ecological complexity and context dependence. The ecophysiology of whole-plant carbon allocation could thus elucidate the ecology and evolution of plant mutualisms. If mutualisms are costly to plants, then they must be important but frequently underestimated sinks in the terrestrial carbon cycle.

  20. Mutual Information Rate and Bounds for It

    PubMed Central

    Baptista, Murilo S.; Rubinger, Rero M.; Viana, Emilson R.; Sartorelli, José C.; Parlitz, Ulrich; Grebogi, Celso

    2012-01-01

    The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two time series (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators. PMID:23112809

  1. Networks in financial markets based on the mutual information rate.

    PubMed

    Fiedor, Paweł

    2014-05-01

    In the last few years there have been many efforts in econophysics studying how network theory can facilitate understanding of complex financial markets. These efforts consist mainly of the study of correlation-based hierarchical networks. This is somewhat surprising as the underlying assumptions of research looking at financial markets are that they are complex systems and thus behave in a nonlinear manner, which is confirmed by numerous studies, making the use of correlations which are inherently dealing with linear dependencies only baffling. In this paper we introduce a way to incorporate nonlinear dynamics and dependencies into hierarchical networks to study financial markets using mutual information and its dynamical extension: the mutual information rate. We show that this approach leads to different results than the correlation-based approach used in most studies, on the basis of 91 companies listed on the New York Stock Exchange 100 between 2003 and 2013, using minimal spanning trees and planar maximally filtered graphs.

  2. The Mutual Impedance Probe (RPC-MIP) onboard ROSETTA

    NASA Astrophysics Data System (ADS)

    Henri, Pierre; Lebreton, Jean-Pierre; Béghin, Christian; Décréau, Pierrette; Grard, Réjean; Hamelin, Michel; Mazelle, Christian; Randriamboarison, Orélien; Schmidt, Walter; Winterhalter, Daniel; Aouad, Youcef; Lagoutte, Dominique; Vallières, Xavier

    2014-05-01

    The ROSETTA mission will reach the comet 67P/Churyumov-Gerasimenko in August 2014 and enable, for the first time, the in situ survey of a comet activity during along orbit. On board the ROSETTA orbiter, the Mutual Impedance Probe (MIP) is one of the instruments of the Rosetta Plasma Consortium (RPC) that aims at monitoring the cometary plasma environment. MIP is a quadrupolar probe that measures the frequency response of the coupling impedance between two emitting and two receiving dipoles. The electron density and temperature are derived from the resonance peak and the interference pattern of the mutual impedance spectrum. We will describe this instrument and discuss the preliminary results obtained during the third ROSETTA Earth flyby to show its expected capabilities. The RPC switch ON for the post-hibernation recommissioning is planned at the end of March. The health status of the instrument will be discussed.

  3. Mutualism supports biodiversity when the direct competition is weak

    PubMed Central

    Pascual-García, Alberto; Bastolla, Ugo

    2017-01-01

    A key question of theoretical ecology is which properties of ecosystems favour their stability and help maintaining biodiversity. This question recently reconsidered mutualistic systems, generating intense controversy about the role of mutualistic interactions and their network architecture. Here we show analytically and verify with simulations that reducing the effective interspecific competition and the propagation of perturbations positively influences structural stability against environmental perturbations, enhancing persistence. Noteworthy, mutualism reduces the effective interspecific competition only when the direct interspecific competition is weaker than a critical value. This critical competition is in almost all cases larger in pollinator networks than in random networks with the same connectance. Highly connected mutualistic networks reduce the propagation of environmental perturbations, a mechanism reminiscent of MacArthur’s proposal that ecosystem complexity enhances stability. Our analytic framework rationalizes previous contradictory results, and it gives valuable insight on the complex relationship between mutualism and biodiversity. PMID:28232740

  4. Networks in financial markets based on the mutual information rate

    NASA Astrophysics Data System (ADS)

    Fiedor, Paweł

    2014-05-01

    In the last few years there have been many efforts in econophysics studying how network theory can facilitate understanding of complex financial markets. These efforts consist mainly of the study of correlation-based hierarchical networks. This is somewhat surprising as the underlying assumptions of research looking at financial markets are that they are complex systems and thus behave in a nonlinear manner, which is confirmed by numerous studies, making the use of correlations which are inherently dealing with linear dependencies only baffling. In this paper we introduce a way to incorporate nonlinear dynamics and dependencies into hierarchical networks to study financial markets using mutual information and its dynamical extension: the mutual information rate. We show that this approach leads to different results than the correlation-based approach used in most studies, on the basis of 91 companies listed on the New York Stock Exchange 100 between 2003 and 2013, using minimal spanning trees and planar maximally filtered graphs.

  5. Mutualism supports biodiversity when the direct competition is weak

    NASA Astrophysics Data System (ADS)

    Pascual-García, Alberto; Bastolla, Ugo

    2017-02-01

    A key question of theoretical ecology is which properties of ecosystems favour their stability and help maintaining biodiversity. This question recently reconsidered mutualistic systems, generating intense controversy about the role of mutualistic interactions and their network architecture. Here we show analytically and verify with simulations that reducing the effective interspecific competition and the propagation of perturbations positively influences structural stability against environmental perturbations, enhancing persistence. Noteworthy, mutualism reduces the effective interspecific competition only when the direct interspecific competition is weaker than a critical value. This critical competition is in almost all cases larger in pollinator networks than in random networks with the same connectance. Highly connected mutualistic networks reduce the propagation of environmental perturbations, a mechanism reminiscent of MacArthur's proposal that ecosystem complexity enhances stability. Our analytic framework rationalizes previous contradictory results, and it gives valuable insight on the complex relationship between mutualism and biodiversity.

  6. Driven diffusive systems with mutually interactive Langmuir kinetics

    NASA Astrophysics Data System (ADS)

    Vuijk, H. D.; Rens, R.; Vahabi, M.; MacKintosh, F. C.; Sharma, A.

    2015-03-01

    We investigate the simple one-dimensional driven model, the totally asymmetric exclusion process, coupled to mutually interactive Langmuir kinetics. This model is motivated by recent studies on clustering of motor proteins on microtubules. In the proposed model, the attachment and detachment rates of a particle are modified depending upon the occupancy of neighboring sites. We first obtain continuum mean-field equations and in certain limiting cases obtain analytic solutions. We show how mutual interactions increase (decrease) the effects of boundaries on the phase behavior of the model. We perform Monte Carlo simulations and demonstrate that our analytical approximations are in good agreement with the numerics over a wide range of model parameters. We present phase diagrams over a selective range of parameters.

  7. An Efficient Algorithm for Direction Finding against Unknown Mutual Coupling

    PubMed Central

    Wang, Weijiang; Ren, Shiwei; Ding, Yingtao; Wang, Haoyu

    2014-01-01

    In this paper, an algorithm of direction finding is proposed in the presence of unknown mutual coupling. The preliminary direction of arrival (DOA) is estimated using the whole array for high resolution. Further refinement can then be conducted by estimating the angularly dependent coefficients (ADCs) with the subspace theory. The mutual coupling coefficients are finally determined by solving the least squares problem with all of the ADCs utilized without discarding any. Simulation results show that the proposed method can achieve better performance at a low signal-to-noise ratio (SNR) with a small-sized array and is more robust, compared with the similar processes employing the initial DOA estimation and further improvement iteratively. PMID:25347587

  8. An efficient algorithm for direction finding against unknown mutual coupling.

    PubMed

    Wang, Weijiang; Ren, Shiwei; Ding, Yingtao; Wang, Haoyu

    2014-10-24

    In this paper, an algorithm of direction finding is proposed in the presence of unknown mutual coupling. The preliminary direction of arrival (DOA) is estimated using the whole array for high resolution. Further refinement can then be conducted by estimating the angularly dependent coefficients (ADCs) with the subspace theory. The mutual coupling coefficients are finally determined by solving the least squares problem with all of the ADCs utilized without discarding any. Simulation results show that the proposed method can achieve better performance at a low signal-to-noise ratio (SNR) with a small-sized array and is more robust, compared with the similar processes employing the initial DOA estimation and further improvement iteratively.

  9. Self-mixing interferometry with mutual independent orthogonal polarized light.

    PubMed

    Zhang, Shaohui; Zhang, Shulian; Tan, Yidong; Sun, Liqun

    2016-02-15

    A self-mixing interferometry with mutual independent orthogonal polarized light is introduced. Its most important feature is that two mutual independent orthogonal lights are used as measuring and reference light. Frequency shifting and polarization multiplexing technologies are used in the proposed optical system. Phase variation of the two orthogonal polarized beams is simultaneously measured through heterodyne demodulation with a lock-in amplifier. The phase difference of the orthogonal polarized light accurately reflects the target displacement. The target in this system is a non-cooperative object which is different from a traditional Michelson interferometer. The primary experimental results show that this kind of self-mixing interferometry is very feasible. Under typical room conditions, the system's short-term resolution is better than 2 nm.

  10. Breakdown and delayed cospeciation in the arbuscular mycorrhizal mutualism

    PubMed Central

    Merckx, Vincent; Bidartondo, Martin I

    2008-01-01

    The ancient arbuscular mycorrhizal association between the vast majority of plants and the fungal phylum Glomeromycota is a dominant nutritional mutualism worldwide. In the mycorrhizal mutualism, plants exchange photosynthesized carbohydrates for mineral nutrients acquired by fungi from the soil. This widespread cooperative arrangement is broken by ‘cheater’ plant species that lack the ability to photosynthesize and thus become dependent upon three-partite linkages (cheater–fungus–photosynthetic plant). Using the first fine-level coevolutionary analysis of mycorrhizas, we show that extreme fidelity towards fungi has led cheater plants to lengthy evolutionary codiversification. Remarkably, the plants' evolutionary history closely mirrors that of their considerably older mycorrhizal fungi. This demonstrates that one of the most diffuse mutualistic networks is vulnerable to the emergence, persistence and speciation of highly specific cheaters. PMID:18270159

  11. Dispersal Mutualism Incorporated into Large-Scale, Infrequent Disturbances.

    PubMed

    Parker, V Thomas

    2015-01-01

    Because of their influence on succession and other community interactions, large-scale, infrequent natural disturbances also should play a major role in mutualistic interactions. Using field data and experiments, I test whether mutualisms have been incorporated into large-scale wildfire by whether the outcomes of a mutualism depend on disturbance. In this study a seed dispersal mutualism is shown to depend on infrequent, large-scale disturbances. A dominant shrubland plant (Arctostaphylos species) produces seeds that make up a persistent soil seed bank and requires fire to germinate. In post-fire stands, I show that seedlings emerging from rodent caches dominate sites experiencing higher fire intensity. Field experiments show that rodents (Perimyscus californicus, P. boylii) do cache Arctostaphylos fruit and bury most seed caches to a sufficient depth to survive a killing heat pulse that a fire might drive into the soil. While the rodent dispersal and caching behavior itself has not changed compared to other habitats, the environmental transformation caused by wildfire converts the caching burial of seed from a dispersal process to a plant fire adaptive trait, and provides the context for stimulating subsequent life history evolution in the plant host.

  12. The Evolution of Mutual Mate Choice under Direct Benefits.

    PubMed

    Courtiol, Alexandre; Etienne, Loïc; Feron, Romain; Godelle, Bernard; Rousset, François

    2016-11-01

    In nature, the intensity of mate choice (i.e., choosiness) is highly variable within and between sexes. Despite growing empirical evidence of male and/or mutual mate choice, theoretical investigations of the joint evolution of female and male choosiness are few. In addition, previous approaches have often assumed an absence of trade-off between the direct benefits per mating and the lower mating rate that results from being choosy. Here we model the joint evolution of female and male choosiness when it is solely ruled by this fundamental trade-off. We show that this trade-off can generate a diversity of stable combinations of choosiness. Mutual mate choice can evolve only if both females and males exhibit long latency after mating. Furthermore, we show that an increase in choosiness in one sex does not necessarily prevent the evolution of mutual mate choice; the outcome depends on details shaping the trade-off: the life history, the decision rule for mate choice, and how the fecundity of a pair is shaped by the quality of both individuals. Last, we discuss the power of the sensitivity of the relative searching time (i.e., of the proportion of a lifetime spent searching for mates) as a predictor of the joint evolution of choosiness.

  13. Dispersal Mutualism Incorporated into Large-Scale, Infrequent Disturbances

    PubMed Central

    Parker, V. Thomas

    2015-01-01

    Because of their influence on succession and other community interactions, large-scale, infrequent natural disturbances also should play a major role in mutualistic interactions. Using field data and experiments, I test whether mutualisms have been incorporated into large-scale wildfire by whether the outcomes of a mutualism depend on disturbance. In this study a seed dispersal mutualism is shown to depend on infrequent, large-scale disturbances. A dominant shrubland plant (Arctostaphylos species) produces seeds that make up a persistent soil seed bank and requires fire to germinate. In post-fire stands, I show that seedlings emerging from rodent caches dominate sites experiencing higher fire intensity. Field experiments show that rodents (Perimyscus californicus, P. boylii) do cache Arctostaphylos fruit and bury most seed caches to a sufficient depth to survive a killing heat pulse that a fire might drive into the soil. While the rodent dispersal and caching behavior itself has not changed compared to other habitats, the environmental transformation caused by wildfire converts the caching burial of seed from a dispersal process to a plant fire adaptive trait, and provides the context for stimulating subsequent life history evolution in the plant host. PMID:26151560

  14. Conceptual Alignment: How Brains Achieve Mutual Understanding.

    PubMed

    Stolk, Arjen; Verhagen, Lennart; Toni, Ivan

    2016-03-01

    We share our thoughts with other minds, but we do not understand how. Having a common language certainly helps, but infants' and tourists' communicative success clearly illustrates that sharing thoughts does not require signals with a pre-assigned meaning. In fact, human communicators jointly build a fleeting conceptual space in which signals are a means to seek and provide evidence for mutual understanding. Recent work has started to capture the neural mechanisms supporting those fleeting conceptual alignments. The evidence suggests that communicators and addressees achieve mutual understanding by using the same computational procedures, implemented in the same neuronal substrate, and operating over temporal scales independent from the signals' occurrences.

  15. Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs

    PubMed Central

    Floyd, Desiree; Purow, Benjamin

    2014-01-01

    MicroRNAs are small noncoding RNAs encoded in eukaryotic genomes that have been found to play critical roles in most biological processes, including cancer. This is true for glioblastoma, the most common and lethal primary brain tumor, for which microRNAs have been shown to strongly influence cell viability, stem cell characteristics, invasiveness, angiogenesis, metabolism, and immune evasion. Developing microRNAs as prognostic markers or as therapeutic agents is showing increasing promise and has potential to reach the clinic in the next several years. This succinct review summarizes current progress and future directions in this exciting and steadily expanding field. PMID:24723563

  16. Periodic solutions and stationary distribution of mutualism models in random environments

    NASA Astrophysics Data System (ADS)

    Zhang, Xinhong; Jiang, Daqing; Alsaedi, Ahmed; Hayat, Tasawar

    2016-10-01

    This paper is concerned with mutualism models in random environments. For the periodic mutualism model disturbed by white noise, using Has'minskii theory of periodic solution, we show that this model admits a nontrivial positive periodic solution. Then sufficient conditions for the existence and global attractivity of the boundary periodic solutions are established. For the mutualism model disturbed by both white noise and telephone noise, sufficient conditions for positive recurrence and the existence of ergodic stationary distribution of the solution are established. Finally, examples are introduced to illustrate the results developed.

  17. Noise and time delay: Suppressed population explosion of the mutualism system

    NASA Astrophysics Data System (ADS)

    Nie, L. R.; Mei, D. C.

    2007-07-01

    We have analyzed effects of noise and time delay in a classical Lotka-Volterra model of mutualism system. We show that the consideration of the noise and the time delay change drastically the behavior of the system in the deterministic case. To a certain degree, the noise or the time delay can suppress the population explosion of the mutualism system, which takes place in the deterministic case, however, the average species population of system with only the noise or the time delay does not converge. Combination of the noise and the time delay completely suppress the population explosion of the mutualism system.

  18. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

    PubMed Central

    Sun, Mengge; Zhou, Xiaoya; Chen, Lili; Huang, Shishu; Leung, Victor; Wu, Nan; Pan, Haobo; Zhen, Wanxin; Lu, William; Peng, Songlin

    2016-01-01

    MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed. PMID:27073801

  19. TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

    PubMed

    Fiorillo, Alyson A; Heier, Christopher R; Novak, James S; Tully, Christopher B; Brown, Kristy J; Uaesoontrachoon, Kitipong; Vila, Maria C; Ngheim, Peter P; Bello, Luca; Kornegay, Joe N; Angelini, Corrado; Partridge, Terence A; Nagaraju, Kanneboyina; Hoffman, Eric P

    2015-09-08

    The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.

  20. MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma

    PubMed Central

    Roccaro, Aldo M.; Sacco, Antonio; Thompson, Brian; Leleu, Xavier; Azab, Abdel Kareem; Azab, Feda; Runnels, Judith; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Lin, Charles P.; Ribatti, Domenico; Rollins, Barrett J.; Witzig, Thomas E.; Anderson, Kenneth C.

    2009-01-01

    Detailed genomic studies have shown that cytogenetic abnormalities contribute to multiple myeloma (MM) pathogenesis and disease progression. Nevertheless, little is known about the characteristics of MM at the epigenetic level and specifically how microRNAs regulate MM progression in the context of the bone marrow milieu. Therefore, we performed microRNA expression profiling of bone marrow derived CD138+ MM cells versus their normal cellular counterparts and validated data by qRT-PCR. We identified a MM-specific microRNA signature characterized by down-expression of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/-181a/-181b (P < .01). We investigated the functional role of microRNA-15a and -16 and showed that they regulate proliferation and growth of MM cells in vitro and in vivo by inhibiting AKT serine/threonine-protein-kinase (AKT3), ribosomal-protein-S6, MAP-kinases, and NF-κB-activator MAP3KIP3. Moreover, miRNA-15a and -16 exerted their anti-MM activity even in the context of the bone marrow milieu in vitro and in vivo. These data indicate that microRNAs play a pivotal role in the biology of MM and represent important targets for novel therapies in MM. PMID:19401561

  1. Myogenic factors that regulate expression of muscle-specific microRNAs.

    PubMed

    Rao, Prakash K; Kumar, Roshan M; Farkhondeh, Mina; Baskerville, Scott; Lodish, Harvey F

    2006-06-06

    Since their discovery as key regulators of early animal development, microRNAs now are recognized as widespread regulators of gene expression. Despite their abundance, little is known regarding the regulation of microRNA biogenesis. We show that three highly conserved muscle-specific microRNAs, miR-1, miR-133 and miR-206, are robustly induced during the myoblast-myotube transition, both in primary human myoblasts and in the mouse mesenchymal C2C12 stem cell line. These microRNAs were not induced during osteogenic conversion of C2C12 cells. Moreover, both loci encoding miR-1, miR-1-1, and miR-1-2, and two of the three encoding miR-133, miR-133a-1 and miR-133a-2, are strongly induced during myogenesis. Some of the induced microRNAs are in intergenic regions, whereas two are transcribed in the opposite direction to the nonmuscle-specific gene in which they are embedded. By using CHIP analysis, we demonstrate that the myogenic factors Myogenin and MyoD bind to regions upstream of these microRNAs and, therefore, are likely to regulate their expression. Because miR-1 and miR-206 are predicted to repress similar mRNA targets, our work suggests that induction of these microRNAs is important in regulating the expression of muscle-specific proteins.

  2. Stochastic mutualism model with Lévy jumps

    NASA Astrophysics Data System (ADS)

    Liu, Qun; Jiang, Daqing; Shi, Ningzhong; Hayat, Tasawar; Alsaedi, Ahmed

    2017-02-01

    In this paper, we consider a stochastic mutualism model with Lévy jumps. First of all, we show that the positive solution of the system is stochastically ultimate bounded. Then under a simple assumption, we establish sufficient and necessary conditions for the stochastic permanence and extinction of the system. The results show an important property of the Lévy jumps: they are unfavorable for the permanence of the species. Moreover, when there are no Lévy jumps, we show that there is a unique ergodic stationary distribution of the corresponding system under certain conditions. Some numerical simulations are introduced to validate the theoretical results.

  3. Mutualism breakdown in breadfruit domestication

    PubMed Central

    Xing, Xiaoke; Koch, Alexander M.; Jones, A. Maxwell P.; Ragone, Diane; Murch, Susan; Hart, Miranda M.

    2012-01-01

    During the process of plant domestication, below-ground communities are rarely considered. Some studies have attempted to understand the changes in root symbionts owing to domestication, but little is known about how it influences mycorrhizal response in domesticated crops. We hypothesized that selection for above-ground traits may also result in decreased mycorrhizal abundance in roots. Breadfruit (Artocarpus sp.) has a long domestication history, with a strong geographical movement of cultivars from west to east across the Melanesian and Polynesian islands. Our results clearly show a decrease in arbuscular mycorrhizas (AMs) along a domestication gradient from wild to recently derived cultivars. We showed that the vesicular and arbuscular colonization rate decreased significantly in more recently derived breadfruit cultivars. In addition, molecular analyses of breadfruit roots indicated that AM fungal species richness also responded along the domestication gradient. These results suggest that human-driven selection for plant cultivars can have unintended effects on below-ground mutualists, with potential impacts on the stress tolerance of crops and long-term food security. PMID:21920983

  4. Mutualism breakdown in breadfruit domestication.

    PubMed

    Xing, Xiaoke; Koch, Alexander M; Jones, A Maxwell P; Ragone, Diane; Murch, Susan; Hart, Miranda M

    2012-03-22

    During the process of plant domestication, below-ground communities are rarely considered. Some studies have attempted to understand the changes in root symbionts owing to domestication, but little is known about how it influences mycorrhizal response in domesticated crops. We hypothesized that selection for above-ground traits may also result in decreased mycorrhizal abundance in roots. Breadfruit (Artocarpus sp.) has a long domestication history, with a strong geographical movement of cultivars from west to east across the Melanesian and Polynesian islands. Our results clearly show a decrease in arbuscular mycorrhizas (AMs) along a domestication gradient from wild to recently derived cultivars. We showed that the vesicular and arbuscular colonization rate decreased significantly in more recently derived breadfruit cultivars. In addition, molecular analyses of breadfruit roots indicated that AM fungal species richness also responded along the domestication gradient. These results suggest that human-driven selection for plant cultivars can have unintended effects on below-ground mutualists, with potential impacts on the stress tolerance of crops and long-term food security.

  5. A consumer-resource approach to the density-dependent population dynamics of mutualism.

    PubMed

    Holland, J Nathaniel; DeAngelis, Donald L

    2010-05-01

    Like predation and competition, mutualism is now recognized as a consumer-resource (C-R) interaction, including, in particular, bi-directional (e.g., coral, plant-mycorrhizae) and uni-directional (e.g., ant-plant defense, plant-pollinator) C-R mutualisms. Here, we develop general theory for the density-dependent population dynamics of mutualism based on the C-R mechanism of interspecific interaction. To test the influence of C-R interactions on the dynamics and stability of bi- and uni-directional C-R mutualisms, we developed simple models that link consumer functional response of one mutualistic species with the resources supplied by another. Phase-plane analyses show that the ecological dynamics of C-R mutualisms are stable in general. Most transient behavior leads to an equilibrium of mutualistic coexistence, at which both species densities are greater than in the absence of interactions. However, due to the basic nature of C-R interactions, certain density-dependent conditions can lead to C-R dynamics characteristic of predator-prey interactions, in which one species overexploits and causes the other to go extinct. Consistent with empirical phenomena, these results suggest that the C-R interaction can provide a broad mechanism for understanding density-dependent population dynamics of mutualism. By unifying predation, competition, and mutualism under the common ecological framework of consumer-resource theory, we may also gain a better understanding of the universal features of interspecific interactions in general.

  6. A consumer-resource approach to the density-dependent population dynamics of mutualism

    USGS Publications Warehouse

    Holland, J. Nathaniel; DeAngelis, Donald L.

    2010-01-01

    Like predation and competition, mutualism is now recognized as a consumer resource (C-R) interaction, including, in particular, bi-directional (e.g., coral, plant- mycorrhizae) and uni-directional (e.g., ant-plant defense, plant-pollinator) C-R mutualisms. Here, we develop general theory for the density-dependent population dynamics of mutualism based on the C-R mechanism of interspecific interaction. To test the influence of C-R interactions on the dynamics and stability of bi- and uni-directional C-R mutualisms, we developed simple models that link consumer functional response of one mutualistic species with the resources supplied by another. Phase-plane analyses show that the ecological dynamics of C-R mutualisms are stable in general. Most transient behavior leads to an equilibrium of mutualistic coexistence, at which both species densities are greater than in the absence of interactions. However, due to the basic nature of C-R interactions, certain density-dependent conditions can lead to C-R dynamics characteristic of predator-prey interactions, in which one species overexploits and causes the other to go extinct. Consistent with empirical phenomena, these results suggest that the C-R interaction can provide a broad mechanism for understanding density-dependent population dynamics of mutualism. By unifying predation, competition, and mutualism under the common ecological framework of consumer-resource theory, we may also gain a better understanding of the universal features of interspecific interactions in general.

  7. Competition as a mechanism structuring mutualisms

    Treesearch

    Robert J. Warren; Itamar Giladi; Mark A. Bradford

    2014-01-01

    Summary 1. Hutchinsonian niche theory posits that organisms have fundamental abiotic resource requirements from which they are limited by competition. Organisms also have fundamental biotic requirements, such as mutualists, for which they also might compete. 2. We test this idea with a widespread ant–plant mutualism. Ant-mediated seed dispersal (myrmecochory) in...

  8. Mutual Group Hypnosis: A Social Interaction Analysis.

    ERIC Educational Resources Information Center

    Sanders, Shirley

    Mutual Group Hypnosis is discussed in terms of its similarity to group dynamics in general and in terms of its similarity to a social interaction program (Role Modeling) designed to foster the expression of warmth and acceptance among group members. Hypnosis also fosters a regression to prelogical thought processes in the service of the ego. Group…

  9. Mutual Group Hypnosis: A Social Interaction Analysis.

    ERIC Educational Resources Information Center

    Sanders, Shirley

    Mutual Group Hypnosis is discussed in terms of its similarity to group dynamics in general and in terms of its similarity to a social interaction program (Role Modeling) designed to foster the expression of warmth and acceptance among group members. Hypnosis also fosters a regression to prelogical thought processes in the service of the ego. Group…

  10. Do Mutual Children Cement Bonds in Stepfamilies?

    ERIC Educational Resources Information Center

    Ganong, Lawrence H.; Coleman, Marilyn

    1988-01-01

    Interviewed 105 midwestern stepfamilies, 39 of whom had reproduced together. Found no significant differences between families with mutual children and those without in terms of marital adjustment, stepparent- and parent-child relationships, and stepfamily affect. It was not possible to predict which families were most likely to reproduce together…

  11. Mutual diffusion of interacting membrane proteins.

    PubMed Central

    Abney, J R; Scalettar, B A; Owicki, J C

    1989-01-01

    The generalized Stokes-Einstein equation is used, together with the two-dimensional pressure equation, to analyze mutual diffusion in concentrated membrane systems. These equations can be used to investigate the role that both direct and hydrodynamic interactions play in determining diffusive behavior. Here only direct interactions are explicitly incorporated into the theory at high densities; however, both direct and hydrodynamic interactions are analyzed for some dilute solutions. We look at diffusion in the presence of weak attractions, soft repulsions, and hard-core repulsions. It is found that, at low densities, attractions retard mutual diffusion while repulsions enhance it. Mechanistically, attractions tend to tether particles together and oppose the dissipation of gradients or fluctuations in concentration, while repulsions provide a driving force that pushes particles apart. At higher concentrations, changes in the structure of the fluid enhance mutual diffusion even in the presence of attractions. It is shown that the theoretical description of postelectrophoresis relaxation and fluorescence correlation spectroscopy experiments must be modified if interacting systems are studied. The effects of interactions on mutual diffusion coefficients have probably already been seen in postelectrophoresis relaxation experiments. PMID:2775829

  12. Empowering Public Welfare Workers through Mutual Support.

    ERIC Educational Resources Information Center

    Sherman, Wendy Ruth; Wenocur, Stanley

    1983-01-01

    Examines the organizational binds facing social workers concerned with the provision of services to clients in times of fiscal restraint. Suggests a mutual support group as a step toward empowerment. Workers may shift from a support group to a coalition for action as change agents within institutional settings. (JAC)

  13. Do Mutual Children Cement Bonds in Stepfamilies?

    ERIC Educational Resources Information Center

    Ganong, Lawrence H.; Coleman, Marilyn

    1988-01-01

    Interviewed 105 midwestern stepfamilies, 39 of whom had reproduced together. Found no significant differences between families with mutual children and those without in terms of marital adjustment, stepparent- and parent-child relationships, and stepfamily affect. It was not possible to predict which families were most likely to reproduce together…

  14. Synchronization in human musical rhythms and mutually interacting complex systems

    PubMed Central

    Hennig, Holger

    2014-01-01

    Though the music produced by an ensemble is influenced by multiple factors, including musical genre, musician skill, and individual interpretation, rhythmic synchronization is at the foundation of musical interaction. Here, we study the statistical nature of the mutual interaction between two humans synchronizing rhythms. We find that the interbeat intervals of both laypeople and professional musicians exhibit scale-free (power law) cross-correlations. Surprisingly, the next beat to be played by one person is dependent on the entire history of the other person’s interbeat intervals on timescales up to several minutes. To understand this finding, we propose a general stochastic model for mutually interacting complex systems, which suggests a physiologically motivated explanation for the occurrence of scale-free cross-correlations. We show that the observed long-term memory phenomenon in rhythmic synchronization can be imitated by fractal coupling of separately recorded or synthesized audio tracks and thus applied in electronic music. Though this study provides an understanding of fundamental characteristics of timing and synchronization at the interbrain level, the mutually interacting complex systems model may also be applied to study the dynamics of other complex systems where scale-free cross-correlations have been observed, including econophysics, physiological time series, and collective behavior of animal flocks. PMID:25114228

  15. Synchronization in human musical rhythms and mutually interacting complex systems.

    PubMed

    Hennig, Holger

    2014-09-09

    Though the music produced by an ensemble is influenced by multiple factors, including musical genre, musician skill, and individual interpretation, rhythmic synchronization is at the foundation of musical interaction. Here, we study the statistical nature of the mutual interaction between two humans synchronizing rhythms. We find that the interbeat intervals of both laypeople and professional musicians exhibit scale-free (power law) cross-correlations. Surprisingly, the next beat to be played by one person is dependent on the entire history of the other person's interbeat intervals on timescales up to several minutes. To understand this finding, we propose a general stochastic model for mutually interacting complex systems, which suggests a physiologically motivated explanation for the occurrence of scale-free cross-correlations. We show that the observed long-term memory phenomenon in rhythmic synchronization can be imitated by fractal coupling of separately recorded or synthesized audio tracks and thus applied in electronic music. Though this study provides an understanding of fundamental characteristics of timing and synchronization at the interbrain level, the mutually interacting complex systems model may also be applied to study the dynamics of other complex systems where scale-free cross-correlations have been observed, including econophysics, physiological time series, and collective behavior of animal flocks.

  16. Oscillatory dynamics in a bacterial cross-protection mutualism.

    PubMed

    Yurtsev, Eugene Anatoly; Conwill, Arolyn; Gore, Jeff

    2016-05-31

    Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective cross-protection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil.

  17. Oscillatory dynamics in a bacterial cross-protection mutualism

    PubMed Central

    Yurtsev, Eugene Anatoly; Conwill, Arolyn; Gore, Jeff

    2016-01-01

    Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective cross-protection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil. PMID:27194723

  18. Basolateral amygdala lesions abolish mutual reward preferences in rats.

    PubMed

    Hernandez-Lallement, Julen; van Wingerden, Marijn; Schäble, Sandra; Kalenscher, Tobias

    2016-01-01

    In a recent study, we demonstrated that rats prefer mutual rewards in a Prosocial Choice Task. Here, employing the same task, we show that the integrity of basolateral amygdala was necessary for the expression of mutual reward preferences. Actor rats received bilateral excitotoxic (n=12) or sham lesions (n=10) targeting the basolateral amygdala and were subsequently tested in a Prosocial Choice Task where they could decide between rewarding ("Both Reward") or not rewarding a partner rat ("Own Reward"), either choice yielding identical reward to the actors themselves. To manipulate the social context and control for secondary reinforcement sources, actor rats were paired with either a partner rat (partner condition) or with an inanimate rat toy (toy condition). Sham-operated animals revealed a significant preference for the Both-Reward-option in the partner condition, but not in the toy condition. Amygdala-lesioned animals exhibited significantly lower Both-Reward preferences than the sham group in the partner but not in the toy condition, suggesting that basolateral amygdala was required for the expression of mutual reward preferences. Critically, in a reward magnitude discrimination task in the same experimental setup, both sham-operated and amygdala-lesioned animals preferred large over small rewards, suggesting that amygdala lesion effects were restricted to decision making in social contexts, leaving self-oriented behavior unaffected.

  19. Using MEMo to discover mutual exclusivity modules in cancer.

    PubMed

    Ciriello, Giovanni; Cerami, Ethan; Aksoy, Bulent Arman; Sander, Chris; Schultz, Nikolaus

    2013-03-01

    Although individual tumors show surprisingly diverse genomic alterations, these events tend to occur in a limited number of pathways, and alterations that affect the same pathway tend to not co-occur in the same patient. While pathway analysis has been a powerful tool in cancer genomics, our knowledge of oncogenic pathway modules is incomplete. To systematically identify such modules, we have developed a novel method, Mutual Exclusivity Modules in Cancer (MEMo). The method searches and identifies modules characterized by three properties: (1) member genes are recurrently altered across a set of tumor samples; (2) member genes are known to or are likely to participate in the same biological process; and (3) alteration events within the modules are mutually exclusive. MEMo integrates multiple data types and maps genomic alterations to biological pathways. MEMo's mutual exclusivity uses a statistical model that preserves the number of alterations per gene and per sample. The MEMo software, source code and sample data sets are available for download at: http://cbio.mskcc.org/memo.

  20. Multiple occurrences of mutualism in the yucca moth lineage.

    PubMed Central

    Pellmyr, O; Thompson, J N

    1992-01-01

    The complex mutualism between yuccas and the moths that pollinate their flowers is regarded as one of the most obvious cases of coevolution. Studies of related genera show that at least two of the critical behavioral and life history traits suggested to have resulted from coevolved mutualism in yucca moths are plesiomorphic to the family. Another trait, oviposition into flowers, has evolved repeatedly within the family. One species with these traits, Greya politella, feeds on and pollinates plants of a different family, but pollination occurs through a different component of the oviposition behavior than in the yucca moths. Major differences compared with yucca moths and their hosts are that G. politella only passively pollinates its host and that copollinators often contribute to pollination. This analysis suggests that evolution of mutualism between yuccas and yucca moths may have required few behavioral and life history changes in the moths. The truly coevolved features of this interaction appear to be the evolution of active pollination by the moths, the associated morphological structures in the moths for carrying pollen, and the exclusion of copollinators by yuccas. Images PMID:11607287

  1. MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors.

    PubMed

    Mancikova, Veronika; Castelblanco, Esmeralda; Pineiro-Yanez, Elena; Perales-Paton, Javier; de Cubas, Aguirre A; Inglada-Perez, Lucia; Matias-Guiu, Xavier; Capel, Ismael; Bella, Maria; Lerma, Enrique; Riesco-Eizaguirre, Garcilaso; Santisteban, Pilar; Maravall, Francisco; Mauricio, Didac; Al-Shahrour, Fatima; Robledo, Mercedes

    2015-06-01

    MicroRNA deregulation could be a crucial event in thyroid carcinogenesis. However, current knowledge is based on studies that have used inherently biased methods. Thus, we aimed to define in an unbiased way a list of deregulated microRNAs in well-differentiated thyroid cancer in order to identify diagnostic and prognostic markers. We performed a microRNA deep-sequencing study using the largest well-differentiated thyroid tumor collection reported to date, comprising 127 molecularly characterized tumors with follicular or papillary patterns of growth and available clinical follow-up data, and 17 normal tissue samples. Furthermore, we integrated microRNA and gene expression data for the same tumors to propose targets for the novel molecules identified. Two main microRNA expression profiles were identified: one common for follicular-pattern tumors, and a second for papillary tumors. Follicular tumors showed a notable overexpression of several members of miR-515 family, and downregulation of the novel microRNA miR-1247. Among papillary tumors, top upregulated microRNAs were miR-146b and the miR-221~222 cluster, while miR-1179 was downregulated. BRAF-positive samples displayed extreme downregulation of miR-7 and -204. The identification of the predicted targets for the novel molecules gave insights into the proliferative potential of the transformed follicular cell. Finally, by integrating clinical follow-up information with microRNA expression, we propose a prediction model for disease relapse based on expression of two miRNAs (miR-192 and let-7a) and several other clinicopathological features. This comprehensive study complements the existing knowledge about deregulated microRNAs in the development of well-differentiated thyroid cancer and identifies novel markers associated with recurrence-free survival.

  2. microRNA expression profile of peripheral blood mononuclear cells of Klinefelter syndrome

    PubMed Central

    SUI, WEIGUO; OU, MINGLIN; CHEN, JIEJING; LI, HUAN; LIN, HUA; ZHANG, YUE; LI, WUXIAN; XUE, WEN; TANG, DONGE; GONG, WEIWEI; ZHANG, RUOHAN; LI, FENGYAN; DAI, YONG

    2012-01-01

    microRNAs are a type of small non-coding RNAs which play important roles in post-transcriptional gene regulation, and the characterization of microRNA expression profiling in peripheral blood mononuclear cells (PBMCs) from patients with Klinefelter syndrome requires further investigation. In this study, PBMCs were obtained from patients with Klinefelter syndrome and normal controls. After preparation of small RNA libraries, the two groups of samples were sequenced simultaneously using next generation high-throughput sequencing technology, and novel and known microRNAs were analyzed. A total of 9,772,392 and 9,717,633 small RNA reads were obtained; 8,014,466 (82.01%) and 8,104,423 (83.40%) genome-matched reads, 64 and 49 novel microRNAs were identified in the library of Klinefelter syndrome and the library of healthy controls, respectively. There were 71 known microRNAs with differential expression levels between the two libraries. Clustering of over-represented gene ontology (GO) classes in predicted targets of novel microRNAs in the Klinefelter syndrome library showed that the most significant GO terms were genes involved in the endomembrane system, nucleotide binding and kinase activity. Our data revealed that there are a large number of microRNAs deregulated in PBMCs taken from patients with Klinefelter syndrome, of which certain novel and known microRNAs may be involved in the pathological process of Klinefelter syndrome. Further studies are necessary to determine the roles of microRNAs in the pathological process of Klinefelter syndrome in the future. PMID:23226734

  3. microRNA expression profile of peripheral blood mononuclear cells of Klinefelter syndrome.

    PubMed

    Sui, Weiguo; Ou, Minglin; Chen, Jiejing; Li, Huan; Lin, Hua; Zhang, Yue; Li, Wuxian; Xue, Wen; Tang, Donge; Gong, Weiwei; Zhang, Ruohan; Li, Fengyan; Dai, Yong

    2012-11-01

    microRNAs are a type of small non-coding RNAs which play important roles in post-transcriptional gene regulation, and the characterization of microRNA expression profiling in peripheral blood mononuclear cells (PBMCs) from patients with Klinefelter syndrome requires further investigation. In this study, PBMCs were obtained from patients with Klinefelter syndrome and normal controls. After preparation of small RNA libraries, the two groups of samples were sequenced simultaneously using next generation high-throughput sequencing technology, and novel and known microRNAs were analyzed. A total of 9,772,392 and 9,717,633 small RNA reads were obtained; 8,014,466 (82.01%) and 8,104,423 (83.40%) genome-matched reads, 64 and 49 novel microRNAs were identified in the library of Klinefelter syndrome and the library of healthy controls, respectively. There were 71 known microRNAs with differential expression levels between the two libraries. Clustering of over-represented gene ontology (GO) classes in predicted targets of novel microRNAs in the Klinefelter syndrome library showed that the most significant GO terms were genes involved in the endomembrane system, nucleotide binding and kinase activity. Our data revealed that there are a large number of microRNAs deregulated in PBMCs taken from patients with Klinefelter syndrome, of which certain novel and known microRNAs may be involved in the pathological process of Klinefelter syndrome. Further studies are necessary to determine the roles of microRNAs in the pathological process of Klinefelter syndrome in the future.

  4. microRNA Response to Listeria monocytogenes Infection in Epithelial Cells

    PubMed Central

    Izar, Benjamin; Mannala, Gopala Krishna; Mraheil, Mobarak Abu; Chakraborty, Trinad; Hain, Torsten

    2012-01-01

    microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (ΔinlAB or Δhly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR- 146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following ΔinlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization. PMID:22312311

  5. Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation.

    PubMed

    Santonocito, Manuela; Vento, Marilena; Guglielmino, Maria Rosa; Battaglia, Rosalia; Wahlgren, Jessica; Ragusa, Marco; Barbagallo, Davide; Borzì, Placido; Rizzari, Simona; Maugeri, Marco; Scollo, Paolo; Tatone, Carla; Valadi, Hadi; Purrello, Michele; Di Pietro, Cinzia

    2014-12-01

    To characterize well-represented microRNAs in human follicular fluid (FF) and to ascertain whether they are cargo of FF exosomes and whether they are involved in the regulation of follicle maturation. FF exosomes were characterized by nanosight, flow cytometry, and exosome-specific surface markers. Expression microRNA profiles from total and exosomal FF were compared with those from plasma of the same women. University laboratory and an IVF center. Fifteen healthy women who had undergone intracytoplasmic sperm injection. None. TaqMan low-density array to investigate the expression profile of 384 microRNAs; DataAssist and geNorm for endogenous control identification; significance analysis of microarrays to identify differentially expressed microRNAs; nanosight, flow-cytometry, and bioanalyzer for exosome characterization; bioinformatic tools for microRNAs target prediction, gene ontology, and pathway analysis. We identified 37 microRNAs upregulated in FF as compared with plasma from the same women. Thirty-two were carried by microvesicles that showed the well-characterized exosomal markers CD63 and CD81. These FF microRNAs are involved in critically important pathways for follicle growth and oocyte maturation. Specifically, nine of them target and negatively regulate mRNAs expressed in the follicular microenvironment encoding inhibitors of follicle maturation and meiosis resumption. This study identified a series of exosomal microRNAs that are highly represented in human FF and are involved in follicular maturation. They could represent noninvasive biomarkers of oocyte quality in assisted reproductive technology. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Genetic variants in microRNAs and microRNA target sites predict biochemical recurrence after radical prostatectomy in localized prostate cancer.

    PubMed

    Huang, Shu-Pin; Lévesque, Eric; Guillemette, Chantal; Yu, Chia-Cheng; Huang, Chao-Yuan; Lin, Victor C; Chung, I-Che; Chen, Lih-Chyang; Laverdière, Isabelle; Lacombe, Louis; Fradet, Yves; Chang, Ta-Yuan; Lee, Hong-Zin; Juang, Shin-Hun; Bao, Bo-Ying

    2014-12-01

    Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ-confined prostate cancer who had a median follow-up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single-nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan-Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16-2.21, p for trend = 0.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15-2.08, p for trend = 0.004) and in combined analysis (HR 1.57, 95% CI 1.26-1.96, p for trend <0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and microRNA target sites can be predictive biomarkers for BCR after RP.

  7. Comparative analysis of microRNA expression profiles between A549, A549/DDP and their respective exosomes.

    PubMed

    Qin, Xiaobing; Yu, Shaorong; Xu, Xiaoyue; Shen, Bo; Feng, Jifeng

    2017-06-27

    Exosomes were reported to transport bioactive molecules and influence the biology behavior of recipient cells. In order to study the role of exosomal microRNAs in the mechanism of cisplatin resistance to lung cancer cells, we analyzed the expression profiles of microRNAs in A549, A549/DDP cells and their exosomes by microarray. The results showed that a certain proportion of microRNAs were co-expressed in the cells and exosomes. Linear regression analysis showed that the expression of microRNAs in A549 and A549/DDP cells were strongly correlated with those in their respective exosomes. The expression level of 5 microRNAs (miR-197-5p, miR-4443, miR-642a-3p, miR-27b-3p and miR-100-5p) with the most differential expression were verified by qRT-PCR. The results were consistent with those of the microarray. Target gene prediction and pathway analysis discovered that the microRNAs in the intersections may participate in drug resistance. And the prediction of their association with diseases found that most of these microRNAs was associated with lung cancer. We could draw a preliminary conclusion that microRNAs in exosomes may be involved in the drug resistance of lung cancer cells to cisplatin.

  8. Comparative analysis of microRNA expression profiles between A549, A549/DDP and their respective exosomes

    PubMed Central

    Xu, Xiaoyue; Shen, Bo; Feng, Jifeng

    2017-01-01

    Exosomes were reported to transport bioactive molecules and influence the biology behavior of recipient cells. In order to study the role of exosomal microRNAs in the mechanism of cisplatin resistance to lung cancer cells, we analyzed the expression profiles of microRNAs in A549, A549/DDP cells and their exosomes by microarray. The results showed that a certain proportion of microRNAs were co-expressed in the cells and exosomes. Linear regression analysis showed that the expression of microRNAs in A549 and A549/DDP cells were strongly correlated with those in their respective exosomes. The expression level of 5 microRNAs (miR-197-5p, miR-4443, miR-642a-3p, miR-27b-3p and miR-100-5p) with the most differential expression were verified by qRT-PCR. The results were consistent with those of the microarray. Target gene prediction and pathway analysis discovered that the microRNAs in the intersections may participate in drug resistance. And the prediction of their association with diseases found that most of these microRNAs was associated with lung cancer. We could draw a preliminary conclusion that microRNAs in exosomes may be involved in the drug resistance of lung cancer cells to cisplatin. PMID:28178672

  9. Global microRNA depletion suppresses tumor angiogenesis

    PubMed Central

    Chen, Sidi; Xue, Yuan; Wu, Xuebing; Le, Cong; Bhutkar, Arjun; Bell, Eric L.; Zhang, Feng; Langer, Robert; Sharp, Phillip A.

    2014-01-01

    MicroRNAs delicately regulate the balance of angiogenesis. Here we show that depletion of all microRNAs suppresses tumor angiogenesis. We generated microRNA-deficient tumors by knocking out Dicer1. These tumors are highly hypoxic but poorly vascularized, suggestive of deficient angiogenesis signaling. Expression profiling revealed that angiogenesis genes were significantly down-regulated as a result of the microRNA deficiency. Factor inhibiting hypoxia-inducible factor 1 (HIF-1), FIH1, is derepressed under these conditions and suppresses HIF transcription. Knocking out FIH1 using CRISPR/Cas9-mediated genome engineering reversed the phenotypes of microRNA-deficient cells in HIF transcriptional activity, VEGF production, tumor hypoxia, and tumor angiogenesis. Using multiplexed CRISPR/Cas9, we deleted regions in FIH1 3′ untranslated regions (UTRs) that contain microRNA-binding sites, which derepresses FIH1 protein and represses hypoxia response. These data suggest that microRNAs promote tumor responses to hypoxia and angiogenesis by repressing FIH1. PMID:24788094

  10. Emergence of stable two-colour states in mutually delay-coupled lasers

    NASA Astrophysics Data System (ADS)

    Seifikar, Masoud; Amann, Andreas; Peters, Frank H.

    2017-03-01

    We theoretically investigate a setup of two mutually delay-coupled semiconductor lasers in a face to face configuration, and study the multi-stabilities and symmetry-broken one-colour and two-colour states for this system, for the development of mutually coupled lasers for integration in a Photonic Integrated Circuit (PIC).We show that the stable two-colour exist for the finite distance between lasers.

  11. Plant invasions--the role of mutualisms.

    PubMed

    Richardson, D M; Allsopp, N; D'Antonio, C M; Milton, S J; Rejmánek, M

    2000-02-01

    Many introduced plant species rely on mutualisms in their new habitats to overcome barriers to establishment and to become naturalized and, in some cases, invasive. Mutualisms involving animal-mediated pollination and seed dispersal, and symbioses between plant roots and microbiota often facilitate invasions. The spread of many alien plants, particularly woody ones, depends on pollinator mutualisms. Most alien plants are well served by generalist pollinators (insects and birds), and pollinator limitation does not appear to be a major barrier for the spread of introduced plants (special conditions relating to Ficus and orchids are described). Seeds of many of the most notorious plant invaders are dispersed by animals, mainly birds and mammals. Our review supports the view that tightly coevolved, plant-vertebrate seed dispersal systems are extremely rare. Vertebrate-dispersed plants are generally not limited reproductively by the lack of dispersers. Most mycorrhizal plants form associations with arbuscular mycorrhizal fungi which, because of their low specificity, do not seem to play a major role in facilitating or hindering plant invasions (except possibly on remote islands such as the Galapagos which are poor in arbuscular mycorrhizal fungi). The lack of symbionts has, however, been a major barrier for many ectomycorrhizal plants, notably for Pinus spp. in parts of the southern hemisphere. The roles of nitrogen-fixing associations between legumes and rhizobia and between actinorhizal plants and Frankia spp. in promoting or hindering invasions have been virtually ignored in the invasions literature. Symbionts required to induce nitrogen fixation in many plants are extremely widespread, but intentional introductions of symbionts have altered the invasibility of many, if not most, systems. Some of the world's worst invasive alien species only invaded after the introduction of symbionts. Mutualisms in the new environment sometimes re-unite the same species that form

  12. Investigation of the effect of phytohormone on the expression of microRNA-159a in Arabidopsis thaliana seedlings based on mimic enzyme catalysis systematic electrochemical biosensor.

    PubMed

    Zhou, Yunlei; Wang, Mo; Xu, Zhenning; Ni, Cailing; Yin, Huanshun; Ai, Shiyun

    2014-04-15

    MicroRNAs (miRNAs) play very important roles in plant growth and development as well as phytohormones. More importantly, microRNAs were recently found to be a new growth regulator involved in plant hormone signaling. Therefore, for investigating the expression change of microRNAs in plants exposed to phytohormones and understanding the effect of phytohormones on microRNAs expression, we developed a simple, sensitive, and label-free method for microRNAs biosensing based on mimic enzyme catalysis signal amplification, where carboxylic graphene-hemin hybrid nanosheets was synthesized and used to catalyze the oxidation reaction of hydroquinone in the presence of H2O2 due to the intrinsic peroxidase-like activity of hemin on the carboxylic graphene surface. The electrochemical reduction current of the oxidative product of benzoquinone was depended on the hybridization amount of microRNAs and used to monitor the microRNAs hybridization event. Under optimal detection conditions, the current response was proportional to the logarithm concentration of microRNA-159a from 0.5 pM to 1.0 nM with the detection limit of 0.17 pM (S/N=3). The fabricated biosensor showed highly reproducible (Relative standard deviation (RSD) was 3.53% for 10 biosensors fabricated independently) and detection selectivity (Even discriminating single-base mismatched microRNA sequence). We also found that abscisic acid, a kind of phytohormone, had greatly influence on microRNA-159a expression in Arabidopsis thaliana seedlings. With increasing abscisic acid concentration and prolonging incubation time, both the expression level of microRNA-159a increased. This graphene-hemin-based approach provides a novel avenue to detect microRNA with high sensitivity and selectivity while avoiding laborious label, disadvantages of bio-enzymes and complex operations for microRNAs separation and enrichment, which might be attractive for genetic analysis and clinic biomedical application.

  13. Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients Circulating MicroRNAs

    PubMed Central

    Li, Su-Chen; Khan, Mohid; Caplin, Martyn; Meyer, Tim; Öberg, Kjell; Giandomenico, Valeria

    2015-01-01

    We previously detected and investigated nine altered microRNAs in small intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease. The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be also detected in patient serum samples, 2) investigate a potential somatostatin analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples and 3) elucidate whether the serum microRNA levels in samples collected in different hospitals are predictable and steady. Our results show that tissue microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a and -200a levels are lower in SI-NET untreated patients than in SSA-treated patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215 levels do not show any difference in untreated SI-NET patients and SSA-treated patients at all different stages. Our findings also show that miR-200a exhibits an atypical behavior with high levels in both untreated and SSA-treated patients at liver metastasis stage, and unequivocally never at the earlier stages. Serum samples collected in two hospitals keep alike microRNA level pattern, elucidating that the results are not dependent on samples handling. In conclusion, SI-NET tissue microRNAs are always detectable in untreated and SSA-treated patient serum samples, SSAs play an unknown role in eliciting SSA-treated patients’ microRNA levels higher than in untreated patients, and this study enlightens that miR-200a might be involved in the liver metastasis during SI-NET progression. PMID:25942502

  14. Measurement point selection in damage detection using the mutual information concept

    NASA Astrophysics Data System (ADS)

    Trendafilova, I.; Heylen, W.; Van Brussel, H.

    2001-06-01

    The problem for measurement point selection in damage detection procedures is addressed. The concept of average mutual information is applied in order to find the optimal distance between measurement points. The idea is to select the measurement points in such a way that the taken measurements are independent, i.e. the measurements do not `learn' from each other. The average mutual information can be utilized as a kind of an autocorrelation function for the purpose. It gives the average amount of information that two points `learn' from each other. Thus the minimum of the average mutual information will provide the distance between measurement points with independent measurements. The idea to use the first minimum of the average mutual information is taken from nonlinear dynamics. The proposed approach is demonstrated on a test case. The results show that it is possible to decrease significantly the number of measurement points, without decreasing the precision of the solution.

  15. Detecting dynamical interdependence and generalized synchrony through mutual prediction in a neural ensemble

    NASA Astrophysics Data System (ADS)

    Schiff, Steven J.; So, Paul; Chang, Taeun; Burke, Robert E.; Sauer, Tim

    1996-12-01

    A method to characterize dynamical interdependence among nonlinear systems is derived based on mutual nonlinear prediction. Systems with nonlinear correlation will show mutual nonlinear prediction when standard analysis with linear cross correlation might fail. Mutual nonlinear prediction also provides information on the directionality of the coupling between systems. Furthermore, the existence of bidirectional mutual nonlinear prediction in unidirectionally coupled systems implies generalized synchrony. Numerical examples studied include three classes of unidirectionally coupled systems: systems with identical parameters, nonidentical parameters, and stochastic driving of a nonlinear system. This technique is then applied to the activity of motoneurons within a spinal cord motoneuron pool. The interrelationships examined include single neuron unit firing, the total number of neurons discharging at one time as measured by the integrated monosynaptic reflex, and intracellular measurements of integrated excitatory postsynaptic potentials (EPSP's). Dynamical interdependence, perhaps generalized synchrony, was identified in this neuronal network between simultaneous single unit firings, between units and the population, and between units and intracellular EPSP's.

  16. Dense registration of CHRIS-Proba and Ikonos images using multi-dimensional mutual information maximization

    NASA Astrophysics Data System (ADS)

    Cariou, Claude; Chehdi, Kacem

    2013-10-01

    We investigate the potential of multidimensional mutual information for the registration of multi-spectral remote sensing images. We devise a gradient flow algorithm which iteratively maximizes the multidimensional mutual information with respect to a differentiable displacement map, accounting for partial derivatives of the multivariate joint distribution and the multivariate marginal of the float image with respect to each variable of the mutual information derivative. The resulting terms are shown to weight the band specific gradients of the warp image, and we propose in addition to compute them with a method based on the k-nearest neighbours. We apply our method to the registration of Ikonos and CHRIS-Proba images over the region of Baabdat, Lebanon, for purposes of cedar pines detection. A comparison between (crossed) single band and multi-band registration results obtained shows that using the multidimensional mutual information brings a significant gain in positional accuracy and is suitable for multispectral remote sensing image registration.

  17. Analytical approaches in microRNA therapeutics.

    PubMed

    Batkai, Sandor; Thum, Thomas

    2014-08-01

    MicroRNAs are non-coding oligonucleotides with regulatory roles in virtually all biological processes. Deregulation of microRNAs lead to impaired cellular function and disease development. Thus, microRNAs are of potential diagnostic and therapeutic relevance. Several technology platforms are currently available for quantitative microRNA analysis and profiling, including the most extensively used PCR-based methods. Each of these technologies has its own advantages and limitations. Mass spectrometry combines low-level detectability with high selectivity and has been used for oligonucleotide sequence analysis. Its use for native microRNA analysis has been limited due to the very low abundance and chemical similarity of microRNAs. However, with the advancement of technology, this analytical method has become a powerful complementary tool for comprehensive analysis of native and synthetic microRNAs. This brief review highlights current developments in the field of microRNA analytics, detection techniques for extracellular microRNAs, their synthetic inhibitors, and the dynamics of their interactions. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Modeling Equilibrium of microRNA Expression

    PubMed Central

    Chan, Lawrence W. C.

    2011-01-01

    MicroRNAs are a class of non-coding RNAs and the dysregulated expression of these short RNA molecules was frequently observed in cancer cells. The steady state level of microRNA concentration may differentiate the biological function of the cells between normal and impaired. To understand the steady state or equilibrium of microRNAs, their interactions with transcription factors and target genes need to be explored and visualized through prediction and network analysis algorithms. This article discusses the application of mathematical model for simulating the dynamics of network feedback loop so as to decipher the mechanism of microRNA regulation. PMID:22303331

  19. Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus.

    PubMed

    Topper, Viktoria Y; Walker, Deena M; Gore, Andrea C

    2015-10-15

    This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner.

  20. Rapid and sensitive microRNA detection with laminar flow-assisted dendritic amplification on power-free microfluidic chip.

    PubMed

    Arata, Hideyuki; Komatsu, Hiroshi; Hosokawa, Kazuo; Maeda, Mizuo

    2012-01-01

    Detection of microRNAs, small noncoding single-stranded RNAs, is one of the key topics in the new generation of cancer research because cancer in the human body can be detected or even classified by microRNA detection. This report shows rapid and sensitive microRNA detection using a power-free microfluidic device, which is driven by degassed poly(dimethylsiloxane), thus eliminating the need for an external power supply. MicroRNA is detected by sandwich hybridization, and the signal is amplified by laminar flow-assisted dendritic amplification. This method allows us to detect microRNA of specific sequences at a limit of detection of 0.5 pM from a 0.5 µL sample solution with a detection time of 20 min. Together with the advantages of self-reliance of this device, this method might contribute substantially to future point-of-care early-stage cancer diagnosis.

  1. Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9.

    PubMed

    Åkerblom, Malin; Sachdeva, Rohit; Quintino, Luis; Wettergren, Erika Elgstrand; Chapman, Katie Z; Manfre, Giuseppe; Lindvall, Olle; Lundberg, Cecilia; Jakobsson, Johan

    2013-01-01

    Functional studies of resident microglia require molecular tools for their genetic manipulation. Here we show that microRNA-9-regulated lentiviral vectors can be used for the targeted genetic modification of resident microglia in the rodent brain. Using transgenic reporter mice, we demonstrate that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. The majority of transgene-expressing cells colabels with the microglia marker Iba1. We use this approach to visualize and isolate activated resident microglia without affecting circulating and infiltrating monocytes or macrophages in an excitotoxic lesion model in rat striatum. The microRNA-9-regulated vectors described here are a straightforward and powerful tool that facilitates functional studies of resident microglia.

  2. Altered expression profile of micrornas in gastric stromal tumor.

    PubMed

    Xiao, Jun; Wang, Qi-xian; Zhu, You-qing

    2015-12-01

    MicroRNAs (miRNAs) play important roles in carcinogenesis, but the global miRNA expression profile in gastric stromal tumor tissues remains unclear. This study was to examine the miRNA expression profile in gastric stromal tumor tissues and explore the function of dysregulated miRNAs by performing gene ontology (GO) and pathway enrichment analysis. Total RNA was extracted and purified from 3 pairs of frozen gastric stromal tumor tissues and the adjacent non-tumor tissues by using mirVana™ miRNA isolation kit. The miRNA expression was analyzed with Affymetrix microarrays (version 4.0) containing 2578 human mature microRNA probes. The dysregulated microRNAs were validated by quantitative RT-PCR in 30 pairs of gastric stromal tumor tissues. The target gene of the dysregulated microRNAs was predicted by miRanda, TargetScan and PicTar. GO and pathway enrichment analysis was conducted to examine the potential function of miR-3178 and miR-193a-5p. The results showed that there were 12 differently expressed microRNAs in gastric stromal tumor tissues, among which 10 miRNAs were down-regulated, and 2 were up-regulated (P<0.05). The validation results by RT-PCR were in accordance with those by microRNA microarry. GO analysis found that the target genes of miR-3178 were involved in 5 GO terms and those of miR-193a-5p in 7 GO terms in level 2. Pathway enrichment analysis suggested that miR-3178 and miR-193a-5p were related to 57 and 122 signaling pathways, respectively. It was concluded that gastric stromal tumor displays a unique miRNA signature. This specific expression may become a new diagnostic and prognostic biomarker for gastric stromal tumor. miR-3178 and miR-193a-5p function as suppressive microRNAs, and they may also become diagnosis and treatment targets for gastric stromal tumor.

  3. Tetrahedral DNA nanostructure-based microRNA biosensor coupled with catalytic recycling of the analyte.

    PubMed

    Miao, Peng; Wang, Bidou; Chen, Xifeng; Li, Xiaoxi; Tang, Yuguo

    2015-03-25

    MicroRNAs are not only important regulators of a wide range of cellular processes but are also identified as promising disease biomarkers. Due to the low contents in serum, microRNAs are always difficult to detect accurately . In this study, an electrochemical biosensor for ultrasensitive detection of microRNA based on tetrahedral DNA nanostructure is developed. Four DNA single strands are engineered to form a tetrahedral nanostructure with a pendant stem-loop and modified on a gold electrode surface, which largely enhances the molecular recognition efficiency. Moreover, taking advantage of strand displacement polymerization, catalytic recycling of microRNA, and silver nanoparticle-based solid-state Ag/AgCl reaction, the proposed biosensor exhibits high sensitivity with the limit of detection down to 0.4 fM. This biosensor shows great clinical value and may have practical utility in early diagnosis and prognosis of certain diseases.

  4. [Analysis of microRNA expression profile in serum of patients with electrical burn or thermal burn].

    PubMed

    Ruan, Q F; Jiang, M J; Ye, Z Q; Zhao, C L; Xie, W G

    2017-01-20

    expressed microRNAs in serum of electrical burn group, compared with those in serum of normal control group. Enrichment analysis of KEGG signaling pathway showed that compared with those in serum of normal control group, microRNAs which changed distinctly in serum of electrical burn group took part in the insulin secretion signaling pathway, arrhythmogenic right ventricular cardiomyopathy signaling pathway, hypertrophic cardiomyopathy signaling pathway, glutamatergic synapse signaling pathway, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, glycerophospholipid metabolism, pyrimidine metabolism, serotonergic synapse signaling pathway, etc, while microRNAs which changed distinctly in serum of thermal burn group took part in the tumor transcription misregulation signaling pathway, proteoglycans in tumor signaling pathway, microRNAs in tumor signaling pathway, long-term potentiation signaling pathway, citrate cycle signaling pathway, tumor necrosis factor signaling pathway, focal adhesion signaling pathway, endocytosis signaling pathway, insulin secretion signaling pathway, p53 signaling pathway, and estrogen signaling pathway, etc. Conclusions: MicroRNA expression profiles in serum of electrical and thermal burn are different from that in serum of healthy adult. The signaling pathways enriched with target genes which are regulated by the differentially expressed microRNAs are related to the pathological changes and clinical manifestations after electrical or thermal burn.

  5. Partner manipulation stabilises a horizontally transmitted mutualism.

    PubMed

    Heil, Martin; Barajas-Barron, Alejandro; Orona-Tamayo, Domancar; Wielsch, Natalie; Svatos, Ales

    2014-02-01

    Mutualisms require protection from non-reciprocating exploiters. Pseudomyrmex workers that engage in an obligate defensive mutualism with Acacia hosts feed exclusively on the sucrose-free extrafloral nectar (EFN) that is secreted by their hosts, a behaviour linking ant energy supply directly to host performance and thus favouring reciprocating behaviour. We tested the hypothesis that Acacia hosts manipulate this digestive specialisation of their ant mutualists. Invertase (sucrose hydrolytic) activity in the ant midguts was inhibited by chitinase, a dominant EFN protein. The inhibition occurred quickly in cell-free gut liquids and in native gels and thus likely results from an enzyme-enzyme interaction. Once a freshly eclosed worker ingests EFN as the first diet available, her invertase becomes inhibited and she, thus, continues feeding on host-derived EFN. Partner manipulation acts at the phenotypic level and means that one partner actively controls the phenotype of the other partner to enhance its dependency on host-derived rewards.

  6. Hardware device binding and mutual authentication

    DOEpatents

    Hamlet, Jason R; Pierson, Lyndon G

    2014-03-04

    Detection and deterrence of device tampering and subversion by substitution may be achieved by including a cryptographic unit within a computing device for binding multiple hardware devices and mutually authenticating the devices. The cryptographic unit includes a physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a binding PUF value. The cryptographic unit uses the binding PUF value during an enrollment phase and subsequent authentication phases. During a subsequent authentication phase, the cryptographic unit uses the binding PUF values of the multiple hardware devices to generate a challenge to send to the other device, and to verify a challenge received from the other device to mutually authenticate the hardware devices.

  7. Conditional mutual information and quantum steering

    NASA Astrophysics Data System (ADS)

    Kaur, Eneet; Wang, Xiaoting; Wilde, Mark M.

    2017-08-01

    Quantum steering has recently been formalized in the framework of a resource theory of steering, and several quantifiers have already been introduced. Here, we propose an information-theoretic quantifier for steering called intrinsic steerability, which uses conditional mutual information to measure the deviation of a given assemblage from one having a local-hidden-state model. We thus relate conditional mutual information to quantum steering and introduce monotones that satisfy certain desirable properties. The idea behind the quantifier is to suppress the correlations that can be explained by an inaccessible quantum system and then quantify the remaining intrinsic correlations. A variant of the intrinsic steerability finds operational meaning as the classical communication cost of sending the measurement choice and outcome to an eavesdropper who possesses a purifying system of the underlying bipartite quantum state that is being measured.

  8. Mutual synchronization of weakly coupled gyrotrons

    SciTech Connect

    Rozental, R. M.; Glyavin, M. Yu.; Sergeev, A. S.; Zotova, I. V.; Ginzburg, N. S.

    2015-09-15

    The processes of synchronization of two weakly coupled gyrotrons are studied within the framework of non-stationary equations with non-fixed longitudinal field structure. With the allowance for a small difference of the free oscillation frequencies of the gyrotrons, we found a certain range of parameters where mutual synchronization is possible while a high electronic efficiency is remained. It is also shown that synchronization regimes can be realized even under random fluctuations of the parameters of the electron beams.

  9. Combating isolation: Building mutual mentoring networks

    NASA Astrophysics Data System (ADS)

    Cox, Anne J.

    2015-12-01

    Women physicists can often feel isolated at work. Support from a grant through the ADVANCE program of the National Science Foundation (U.S. government funding) created mutual mentoring networks aimed at combating isolation specifically for women faculty at undergraduate-only institutions. This paper will discuss the organization of one such network, what contributed to its success, some of the outcomes, and how it might be implemented in other contexts.

  10. Mutual Coupling Analysis for Conformal Microstrip Antennas.

    DTIC Science & Technology

    1984-12-01

    coated cylinder. Certain orthogonality properties of the cylindrical vector wave functions [ 15 ] are established in this chapter. The dielectric coated...forms of orthogonal properties of these vector - wave functions have previously been investigated by Stratton [ 15 ] who used a mixed domain of (p,O,X...based upon appropriate Green’s functions are employed to rigorously treat the mutual coupling of microstrip patches on 1) an infinite grounded dielectric

  11. Entanglement patterns in mutually unbiased basis sets

    SciTech Connect

    Lawrence, Jay

    2011-08-15

    A few simply stated rules govern the entanglement patterns that can occur in mutually unbiased basis sets (MUBs) and constrain the combinations of such patterns that can coexist in full complements of MUBs. We consider Hilbert spaces of prime power dimensions (D=p{sup N}), as realized by systems of N prime-state particles, where full complements of D+1 MUBs are known to exist, and we assume only that MUBs are eigenbases of generalized Pauli operators, without using any particular construction. The general rules include the following: (1) In any MUB, a given particle appears either in a pure state or totally entangled and (2) in any full MUB complement, each particle is pure in (p+1) bases (not necessarily the same ones) and totally entangled in the remaining (p{sup N}-p). It follows that the maximum number of product bases is p+1 and, when this number is realized, all remaining (p{sup N}-p) bases in the complement are characterized by the total entanglement of every particle. This ''standard distribution'' is inescapable for two-particle systems (of any p), where only product and generalized Bell bases are admissible MUB types. This and the following results generalize previous results for qubits [Phys. Rev. A 65. 032320 (2002); Phys. Rev. A 72, 062310 (2005)] and qutrits [Phys. Rev. A 70, 012302 (2004)], drawing particularly upon [Phys. Rev. A 72, 062310 (2005)]. With three particles there are three MUB types, and these may be combined in (p+2) different ways to form full complements. With N=4, there are 6 MUB types for p=2, but new MUB types become possible with larger p, and these are essential to realizing full complements. With this example, we argue that new MUB types that show new entanglement patterns should enter with every step in N and, also, when N is a prime plus 1, at a critical p value, p=N-1. Such MUBs should play critical roles in filling complements.

  12. Adaptive expression of microRNA-125a in adipose tissue in response to obesity in mice and men.

    PubMed

    Diawara, Malika R; Hue, Christophe; Wilder, Steven P; Venteclef, Nicolas; Aron-Wisnewsky, Judith; Scott, James; Clément, Karine; Gauguier, Dominique; Calderari, Sophie

    2014-01-01

    MicroRNAs are emerging as new mediators in the regulation of adipose tissue biology and the development of obesity. An important role of microRNA-125a has been suggested in the pathogenesis of insulin resistance (IR). Here, we characterized the function of microRNA-125a in adipose tissue in a context of experimentally-induced IR and obesity in mice and in obese patients. We showed time dependent overexpression of the microRNA in adipose tissue of BALB/c and C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set enrichment analysis (GSEA) identified significantly altered expression patterns of predicted microRNA-125a gene targets in transcriptomic datasets of adipose tissue from HFD-fed mice and obese patients. Among genes that contributed to global enrichment of altered expression of microRNA-125a targets, Thyrotroph embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in adipose tissue in these groups. We showed that Tef expression is reduced in adipose tissue of obese patients following gastric bypass surgery. Our findings indicate that microRNA-125a expression in adipose tissue adapts to IR and may play a role in the development of obesity in mice and obese subjects through uncoupled regulation of the expression of microRNA-125a and its targets.

  13. Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

    PubMed Central

    Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described. PMID:22438871

  14. Identification and pathway analysis of microRNAs with no previous involvement in breast cancer.

    PubMed

    Romero-Cordoba, Sandra; Rodriguez-Cuevas, Sergio; Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described.

  15. Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy

    PubMed Central

    Jo, Peter; Azizian, Azadeh; Salendo, Junius; Kramer, Frank; Bernhardt, Markus; Wolff, Hendrik A.; Gruber, Jens; Grade, Marian; Beißbarth, Tim; Ghadimi, B. Michael; Gaedcke, Jochen

    2017-01-01

    Since the response to chemoradiotherapy in patients with locally advanced rectal cancer is heterogeneous, valid biomarkers are needed to monitor tumor response. Circulating microRNAs are promising candidates, however analyses of circulating microRNAs in rectal cancer are still rare. 111 patients with rectal cancer and 46 age-matched normal controls were enrolled. The expression levels of 30 microRNAs were analyzed in 17 pre-treatment patients’ plasma samples. Differentially regulated microRNAs were validated in 94 independent patients. For 52 of the 94 patients a paired comparison between pre-treatment and post-treatment samples was performed. miR-17, miR-18b, miR-20a, miR-31, and miR-193a_3p, were significantly downregulated in pre-treatment plasma samples of patients with rectal cancer (p < 0.05). miR-29c, miR-30c, and miR-195 showed a trend of differential regulation. After validation, miR-31 and miR-30c were significantly deregulated by a decrease of expression. In 52 patients expression analyses of the 8 microRNAs in matched pre-treatment and post-treatment samples showed a significant decrease for all microRNAs (p < 0.05) after treatment. Expression levels of miR-31 and miR-30c could serve as valid biomarkers if validated in a prospective study. Plasma microRNA expression levels do not necessarily represent miRNA expression levels in tumor tissue. Also, expression levels of microRNAs change during multimodal therapy. PMID:28554991

  16. Control of Antagonistic Components of the Hedgehog Signaling Pathway by microRNAs in Drosophila

    PubMed Central

    Friggi-Grelin, Florence; Lavenant-Staccini, Laurence; Therond, Pascal

    2008-01-01

    Hedgehog (Hh) signaling is critical for many developmental processes and for the genesis of diverse cancers. Hh signaling comprises a series of negative regulatory steps, from Hh reception to gene transcription output. We previously showed that stability of antagonistic regulatory proteins, including the coreceptor Smoothened (Smo), the kinesin-like Costal-2 (Cos2), and the kinase Fused (Fu), is affected by Hh signaling activation. Here, we show that the level of these three proteins is also regulated by a microRNA cluster. Indeed, the overexpression of this cluster and resulting microRNA regulation of the 3′-UTRs of smo, cos2, and fu mRNA decreases the levels of the three proteins and activates the pathway. Further, the loss of the microRNA cluster or of Dicer function modifies the 3′-UTR regulation of smo and cos2 mRNA, confirming that the mRNAs encoding the different Hh components are physiological targets of microRNAs. Nevertheless, an absence of neither the microRNA cluster nor of Dicer activity creates an hh-like phenotype, possibly due to dose compensation between the different antagonistic targets. This study reveals that a single signaling pathway can be targeted at multiple levels by the same microRNAs. PMID:18493062

  17. Toward the promise of microRNAs - Enhancing reproducibility and rigor in microRNA research.

    PubMed

    Witwer, Kenneth W; Halushka, Marc K

    2016-11-01

    The fields of applied and translational microRNA research have exploded in recent years as microRNAs have been implicated across a spectrum of diseases. MicroRNA biomarkers, microRNA therapeutics, microRNA regulation of cellular physiology and even xenomiRs have stimulated great interest, which have brought many researchers into the field. Despite many successes in determining general mechanisms of microRNA generation and function, the application of microRNAs in translational areas has not had as much success. It has been a challenge to localize microRNAs to a given cell type within tissues and assay them reliably. At supraphysiologic levels, microRNAs may regulate hosts of genes that are not the physiologic biochemical targets. Thus the applied and translational microRNA literature is filled with pitfalls and claims that are neither scientifically rigorous nor reproducible. This review is focused on increasing awareness of the challenges of working with microRNAs in translational research and recommends better practices in this area of discovery.

  18. Asymmetric Mutualism in Two- and Three-Dimensional Range Expansions

    NASA Astrophysics Data System (ADS)

    Lavrentovich, Maxim O.; Nelson, David R.

    2014-04-01

    Genetic drift at the frontiers of two-dimensional range expansions of microorganisms can frustrate local cooperation between different genetic variants, demixing the population into distinct sectors. In a biological context, mutualistic or antagonistic interactions will typically be asymmetric between variants. By taking into account both the asymmetry and the interaction strength, we show that the much weaker demixing in three dimensions allows for a mutualistic phase over a much wider range of asymmetric cooperative benefits, with mutualism prevailing for any positive, symmetric benefit. We also demonstrate that expansions with undulating fronts roughen dramatically at the boundaries of the mutualistic phase, with severe consequences for the population genetics along the transition lines.

  19. 78 FR 26424 - Mutual Savings Association Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... Office of the Comptroller of the Currency Mutual Savings Association Advisory Committee AGENCY: Office of... Mutual Savings Association Advisory Committee (MSAAC). DATES: A public meeting of the MSAAC will be held... savings associations, and other issues of concern to the existing mutual savings associations. On the day...

  20. 77 FR 74052 - Mutual Savings Association Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-12

    ... Office of the Comptroller of the Currency Mutual Savings Association Advisory Committee Meeting AGENCY... Mutual Savings Association Advisory Committee (MSAAC or Committee). DATES: A public meeting of the MSAAC... 8:30 a.m. EST. Agenda items include a discussion of the status of the mutual savings association...

  1. 12 CFR 563.74 - Mutual capital certificates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Application form; supporting information. An application for approval of the issuance of mutual capital... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Mutual capital certificates. 563.74 Section 563...-OPERATIONS Securities and Borrowings § 563.74 Mutual capital certificates. (a) General. No savings...

  2. An orb-weaver spider exploits an ant–acacia mutualism for enemy-free space

    PubMed Central

    Styrsky, John D

    2014-01-01

    Exploiters of protection mutualisms are assumed to represent an important threat for the stability of those mutualisms, but empirical evidence for the commonness or relevance of exploiters is limited. Here, I describe results from a manipulative study showing that an orb-weaver spider, Eustala oblonga, inhabits an ant-acacia for protection from predators. This spider is unique in the orb-weaver family in that it associates closely with both a specific host plant and ants. I tested the protective effect of acacia ants on E. oblonga by comparing spider abundance over time on acacias with ants and on acacias from which entire ant colonies were experimentally removed. Both juvenile and adult spider abundance significantly decreased over time on acacias without ants. Concomitantly, the combined abundance of potential spider predators increased over time on acacias without ants. These results suggest that ant protection of the ant-acacia Acacia melanocerus also protects the spiders, thus supporting the hypothesis that E. oblonga exploits the ant–acacia mutualism for enemy-free space. Although E. oblonga takes advantage of the protection services of ants, it likely exacts little to no cost and should not threaten the stability of the ant–acacia mutualism. Indeed, the potential threat of exploiter species to protection mutualisms in general may be limited to species that exploit the material rewards traded in such mutualisms rather than the protection services. PMID:24558583

  3. Evolutionary stability of mutualism: interspecific population regulation as an evolutionarily stable strategy

    USGS Publications Warehouse

    Holland, J. Nathaniel; DeAngelis, Donald L.; Schultz, Stewart T.

    2004-01-01

    Interspecific mutualisms are often vulnerable to instability because low benefit : cost ratios can rapidly lead to extinction or to the conversion of mutualism to parasite–host or predator–prey interactions. We hypothesize that the evolutionary stability of mutualism can depend on how benefits and costs to one mutualist vary with the population density of its partner, and that stability can be maintained if a mutualist can influence demographic rates and regulate the population density of its partner. We test this hypothesis in a model of mutualism with key features of senita cactus (Pachycereus schottii) – senita moth (Upiga virescens) interactions, in which benefits of pollination and costs of larval seed consumption to plant fitness depend on pollinator density. We show that plants can maximize their fitness by allocating resources to the production of excess flowers at the expense of fruit. Fruit abortion resulting from excess flower production reduces pre–adult survival of the pollinating seed–consumer, and maintains its density beneath a threshold that would destabilize the mutualism. Such a strategy of excess flower production and fruit abortion is convergent and evolutionarily stable against invasion by cheater plants that produce few flowers and abort few to no fruit. This novel mechanism of achieving evolutionarily stable mutualism, namely interspecific population regulation, is qualitatively different from other mechanisms invoking partner choice or selective rewards, and may be a general process that helps to preserve mutualistic interactions in nature.

  4. Interactive cooperation and hierarchical operation of microRNA and transcription factor crosstalk in human transcriptional regulatory network.

    PubMed

    Gov, Esra; Arga, Kazim Yalcin

    2016-12-01

    Transcriptional regulation of gene expression is an essential cellular process that is arranged by transcription factors (TFs), microRNAs (miRNA) and their target genes through a variety of mechanisms. Here, we set out to reconstruct a comprehensive transcriptional regulatory network of Homo sapiens consisting of experimentally verified regulatory information on miRNAs, TFs and their target genes. We have performed topological analyses to elucidate the transcriptional regulatory roles of miRNAs and TFs. When we thoroughly investigated the network motifs, different gene regulatory scenarios were observed; whereas, mutual TF-miRNA regulation (interactive cooperation) and hierarchical operation where miRNAs were the upstream regulators of TFs came into prominence. Otherwise, biological process specific subnetworks were also constructed and integration of gene and miRNA expression data on ovarian cancer was achieved as a case study to observe dynamic patterns of the gene expression. Meanwhile, both co-operation and hierarchical operation types were determined in active ovarian cancer and process-specific subnetworks. In addition, the analysis showed that multiple signals from miRNAs were integrated by TFs. Our results demonstrate new insights on the architecture of the human transcriptional regulatory network, and here we present some lessons we gained from deciphering the reciprocal interplay between miRNAs, TFs and their target genes.

  5. Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens.

    PubMed

    Karatas, Omer Faruk; Suer, Ilknur; Yuceturk, Betul; Yilmaz, Mehmet; Oz, Buge; Guven, Gulgun; Cansiz, Harun; Creighton, Chad J; Ittmann, Michael; Ozen, Mustafa

    2016-11-05

    Emerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. In this study we aimed to investigate microRNA profile of cancer stem-like cells (CSLCs) isolated form freshly resected larynx cancer (LCa) tissue samples. CD133 positive (CD133(+)) stem-like cells were isolated from freshly resected LCa tumor specimens. MicroRNA profile of 12 pair of CD133(+) and CD133(-) cells was determined using microRNA microarray and differential expressions of selvected microRNAs were validated by quantitative real time PCR (qRT-PCR). MicroRNA profiling of CD133(+) and CD133(-) LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133(+) larynx CSLCs. qRT-PCR analysis in a total of 25 CD133(+)/CD133(-) sample pairs confirmed the altered expressions of these five microRNAs. Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. Furthermore, in silico analysis revealed that these microRNAs target both cancer and stem-cell associated signaling pathways. Our results showed that certain microRNAs in CD133(+) cells could be used as cancer stem cell markers. Based on these results, we propose that this panel of microRNAs might carry crucial roles in LCa pathogenesis through regulating stem cell properties of tumor cells.

  6. Network-based ranking methods for prediction of novel disease associated microRNAs.

    PubMed

    Le, Duc-Hau

    2015-10-01

    Many studies have shown roles of microRNAs on human disease and a number of computational methods have been proposed to predict such associations by ranking candidate microRNAs according to their relevance to a disease. Among them, machine learning-based methods usually have a limitation in specifying non-disease microRNAs as negative training samples. Meanwhile, network-based methods are becoming dominant since they well exploit a "disease module" principle in microRNA functional similarity networks. Of which, random walk with restart (RWR) algorithm-based method is currently state-of-the-art. The use of this algorithm was inspired from its success in predicting disease gene because the "disease module" principle also exists in protein interaction networks. Besides, many algorithms designed for webpage ranking have been successfully applied in ranking disease candidate genes because web networks share topological properties with protein interaction networks. However, these algorithms have not yet been utilized for disease microRNA prediction. We constructed microRNA functional similarity networks based on shared targets of microRNAs, and then we integrated them with a microRNA functional synergistic network, which was recently identified. After analyzing topological properties of these networks, in addition to RWR, we assessed the performance of (i) PRINCE (PRIoritizatioN and Complex Elucidation), which was proposed for disease gene prediction; (ii) PageRank with Priors (PRP) and K-Step Markov (KSM), which were used for studying web networks; and (iii) a neighborhood-based algorithm. Analyses on topological properties showed that all microRNA functional similarity networks are small-worldness and scale-free. The performance of each algorithm was assessed based on average AUC values on 35 disease phenotypes and average rankings of newly discovered disease microRNAs. As a result, the performance on the integrated network was better than that on individual ones. In

  7. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans.

    PubMed

    Virant-Klun, Irma; Ståhlberg, Anders; Kubista, Mikael; Skutella, Thomas

    2016-01-01

    MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells.

  8. Neuroprotective Effects of MicroRNA-210 on Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Zhou, Xiao-yu; Zhou, Xiao-guang; Cheng, Rui; Liu, Hai-ying; Li, Yong

    2013-01-01

    Objectives. To reveal the effect of microRNA-210 on cell apoptosis caused by HIE. Methods. Postnatal day 7 rats after HI injury were intraventricularly injected with microRNA-210 mimic, microRNA-210 inhibitor, or physiological saline. 72 h after the injection, rats were sacrificed and the left hemispheres were collected. The expression level of microRNA-210 was identified by quantitative real-time PCR analysis. Apoptosis in brain sections was investigated by TUNEL assay. Apoptosis-related protein expressions were studied by Western blot analysis. Results. The results showed that microRNA-210, whose expression was downregulated in the brain 72 h after HI injury, suppressed neuronal apoptosis by inhibiting caspase activity and regulating the balance between bcl-2 and bax levels. Discussion. Recent study demonstrated that microRNA-210 has neuroprotective effects through inhibiting apoptosis in a murine model of HIE. It represents a potential novel therapeutic approach for the treatment of HIE. PMID:24089674

  9. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

    PubMed Central

    Virant-Klun, Irma; Ståhlberg, Anders; Kubista, Mikael; Skutella, Thomas

    2016-01-01

    MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells. PMID:26664407

  10. microRNAs as cancer biomarkers.

    PubMed

    Flatmark, Kjersti; Høye, Eirik; Fromm, Bastian

    2016-01-01

    Since their discovery in 1993, microRNAs (miRNAs) have been identified as important gene regulators in many biological processes and as key molecular players in human disease, including cancer where they show specific pathogenic deregulation. Their remarkable chemical stability, the availability of very sensitive miRNA detection methods and the fact that miRNAs can be extracted from and detected in various kinds of clinically relevant samples, such as solid tissues, body fluids and secretions make them excellent candidate biomarkers. However, no miRNA has yet entered the level of practical clinical relevance. We present a brief background and some key aspects and challenges of miRNAs as cancer biomarkers, we discuss shortfalls and identify possible routes towards the use of miRNAs as reliable biomarkers for cancer.

  11. MicroRNAs as biomarkers in leukemia

    PubMed Central

    Wang, Xinxin; Zhu, Baohua; Huang, Zunnan; Chen, Liyong

    2014-01-01

    Current diagnostic and prognostic markers still exhibit biological limitation and seeking novel molecular biomarkers is crucial for early clinical diagnosis and in the development of novel strategies for leukemia therapy. Emerging evidence showed that dysregulated microRNAs (miRNAs) play important roles in cancer including leukemia. In this review, we summarized recent progress on the role of miRNAs in leukemia, mainly focusing on recent findings that suggest the potential of miRNAs as biomarkers for diagnosis and prognosis. Notably, the circulating miRNAs were also discussed for the fact that they can be detected in body fluids, and thus represent a novel source of promising biomarkers that may be applied to clinical settings. PMID:27358857

  12. MicroRNA therapeutics in neurological disease.

    PubMed

    Greenberg, David S; Soreq, Hermona

    2014-01-01

    Developing microRNA therapeutics for neurological diseases is both a promising opportunity and an extremely challenging topic for several reasons. The promise stems from the very small size of microRNAs, which makes them amenable for manipulation via short synthetic oligonucleotides or engineered viruses. Also, the fact that each microRNA may regulate numerous target transcripts of the same pathway predicts that such manipulations may affect an entire pathway rather than a single gene and gives reason to hope that low dose therapeutic targeting of the top microRNA in such a hierarchic pyramid would suffice to induce a focused change in the entire pyramid. However, these same features, which make microRNAs such promising targets for therapeutic manipulations also present great challenges. Thus the plethora of functional targets for each microRNA in specific cell types is yet far from being elucidated, which implies that the targets to be affected may not be those planned to be manipulated (a risk of 'off-target' effects). Also, the hierarchic order of microRNA regulation is yet unknown, which predicts a risk of complex, multi-leveled consequences following the manipulation of a single microRNA; and the delivery of oligonucleotide therapeutics into the brain is a challenge due to the blood-brain barrier. In this chapter, we briefly outline the current state of knowledge regarding microRNA regulation in different neuropathologies and sketch the emerging principles for the development of microRNA therapeutics for these diseases.We address issues such as modes of delivery and consideration of the inherited and acquired variability between individuals in the susceptibility to such treatments. We further refer in a somewhat more in-depth manner to the issue of manipulating microRNA functioning in the parasympathetic system and the pathway of cholinergic signaling. Beyond the brain and within it, cholinergic signaling controls inflammatory reactions, and microRNA changes

  13. MicroRNA involvement in glioblastoma pathogenesis

    SciTech Connect

    Novakova, Jana; Slaby, Ondrej; Vyzula, Rostislav; Michalek, Jaroslav

    2009-08-14

    MicroRNAs are endogenously expressed regulatory noncoding RNAs. Altered expression levels of several microRNAs have been observed in glioblastomas. Functions and direct mRNA targets for these microRNAs have been relatively well studied over the last years. According to these data, it is now evident, that impairment of microRNA regulatory network is one of the key mechanisms in glioblastoma pathogenesis. MicroRNA deregulation is involved in processes such as cell proliferation, apoptosis, cell cycle regulation, invasion, glioma stem cell behavior, and angiogenesis. In this review, we summarize the current knowledge of miRNA functions in glioblastoma with an emphasis on its significance in glioblastoma oncogenic signaling and its potential to serve as a disease biomarker and a novel therapeutic target in oncology.

  14. Excess mutual catalysis is required for effective evolvability.

    PubMed

    Markovitch, Omer; Lancet, Doron

    2012-01-01

    It is widely accepted that autocatalysis constitutes a crucial facet of effective replication and evolution (e.g., in Eigen's hypercycle model). Other models for early evolution (e.g., by Dyson, Gánti, Varela, and Kauffman) invoke catalytic networks, where cross-catalysis is more apparent. A key question is how the balance between auto- (self-) and cross- (mutual) catalysis shapes the behavior of model evolving systems. This is investigated using the graded autocatalysis replication domain (GARD) model, previously shown to capture essential features of reproduction, mutation, and evolution in compositional molecular assemblies. We have performed numerical simulations of an ensemble of GARD networks, each with a different set of lognormally distributed catalytic values. We asked what is the influence of the catalytic content of such networks on beneficial evolution. Importantly, a clear trend was observed, wherein only networks with high mutual catalysis propensity (p(mc)) allowed for an augmented diversity of composomes, quasi-stationary compositions that exhibit high replication fidelity. We have reexamined a recent analysis that showed meager selection in a single GARD instance and for a few nonstationary target compositions. In contrast, when we focused here on compotypes (clusters of composomes) as targets for selection in populations of compositional assemblies, appreciable selection response was observed for a large portion of the networks simulated. Further, stronger selection response was seen for high p(mc) values. Our simulations thus demonstrate that GARD can help analyze important facets of evolving systems, and indicate that excess mutual catalysis over self-catalysis is likely to be important for the emergence of molecular systems capable of evolutionlike behavior.

  15. Creating a culture of mutual respect.

    PubMed

    Kaplan, Kathryn; Mestel, Pamela; Feldman, David L

    2010-04-01

    The Joint Commission mandates that hospitals seeking accreditation have a process to define and address disruptive behavior. Leaders at Maimonides Medical Center, Brooklyn, New York, took the initiative to create a code of mutual respect that not only requires respectful behavior, but also encourages sensitivity and awareness to the causes of frustration that often lead to inappropriate behavior. Steps to implementing the code included selecting code advocates, setting up a system for mediating disputes, tracking and addressing operational system issues, providing training for personnel, developing a formal accountability process, and measuring the results.

  16. Partner selection in the mycorrhizal mutualism.

    PubMed

    Werner, Gijsbert D A; Kiers, E Toby

    2015-03-01

    Partner selection in the mycorrhizal symbiosis is thought to be a key factor stabilising the mutualism. Both plant hosts and mycorrhizal fungi have been shown to preferentially allocate resources to higher quality partners. This can help maintain underground cooperation, although it is likely that different plant species vary in the spatial precision with which they can select partners. Partner selection in the mycorrhizal symbiosis is presumably context-dependent and can be mediated by factors like (relative) resource abundance and resource fluctuations, competition among mycorrhizas, arrival order and cultivation history. Such factors complicate our current understanding of the importance of partner selection and its effectiveness in stimulating mutualistic cooperation.

  17. Arithmetic, mutually unbiased bases and complementary observables

    SciTech Connect

    Sheppeard, M. D.

    2010-02-15

    Complementary observables in quantum mechanics may be viewed as Frobenius structures in a dagger monoidal category, such as the category of finite dimensional Hilbert spaces over the complex numbers. On the other hand, their properties crucially depend on the discrete Fourier transform and its associated quantum torus, requiring only the finite fields that underlie mutually unbiased bases. In axiomatic topos theory, the complex numbers are difficult to describe and should not be invoked unnecessarily. This paper surveys some fundamentals of quantum arithmetic using finite field complementary observables, with a view considering more general axiom systems.

  18. Identity theory and personality theory: mutual relevance.

    PubMed

    Stryker, Sheldon

    2007-12-01

    Some personality psychologists have found a structural symbolic interactionist frame and identity theory relevant to their work. This frame and theory, developed in sociology, are first reviewed. Emphasized in the review are a multiple identity conception of self, identities as internalized expectations derived from roles embedded in organized networks of social interaction, and a view of social structures as facilitators in bringing people into networks or constraints in keeping them out, subsequently, attention turns to a discussion of the mutual relevance of structural symbolic interactionism/identity theory and personality theory, looking to extensions of the current literature on these topics.

  19. microRNA Decay: Refining microRNA Regulatory Activity.

    PubMed

    Pepin, Genevieve; Gantier, Michael P

    2016-01-01

    MicroRNAs (miRNAs) are short 19-25 nucleotide RNA molecules that impact on most biological processes by regulating the efficiency of messenger RNA (mRNA) translation. To date, most research activities have been focused on the control of miRNA expression and its functional consequences. Nonetheless, much remains unknown about the mechanisms affecting the level of specific miRNAs in the cell, a critical feature impacting their regulatory activity. This review focuses on the factors that regulate the abundance of miRNAs, including synthesis, post-transcriptional modifications, nucleases, target binding, and secretion.

  20. An invasive slug exploits an ant-seed dispersal mutualism.

    PubMed

    Meadley Dunphy, Shannon A; Prior, Kirsten M; Frederickson, Megan E

    2016-05-01

    Plant-animal mutualisms, such as seed dispersal, are often vulnerable to disruption by invasive species. Here, we show for the first time how a non-ant invasive species negatively affects seed dispersal by ants. We examined the effects of several animal species that co-occur in a temperate deciduous forest-including native and invasive seed-dispersing ants (Aphaenogaster rudis and Myrmica rubra, respectively), an invasive slug (Arion subfuscus), and native rodents-on a native myrmecochorous plant, Asarum canadense. We experimentally manipulated ant, slug, and rodent access to seed depots and measured seed removal. We also video-recorded depots to determine which other taxa interact with seeds. We found that A. rudis was the main disperser of seeds and that A. subfuscus consumed elaiosomes without dispersing seeds. Rodent visitation was rare, and rodent exclusion had no significant effect on seed or elaiosome removal. We then used data obtained from laboratory and field mesocosm experiments to determine how elaiosome robbing by A. subfuscus affects seed dispersal by A. rudis and M. rubra. We found that elaiosome robbing by slugs reduced seed dispersal by ants, especially in mesocosms with A. rudis, which picks up seeds more slowly than M. rubra. Taken together, our results show that elaiosome robbing by an invasive slug reduces seed dispersal by ants, suggesting that invasive slugs can have profound negative effects on seed dispersal mutualisms.

  1. Aggressive mimicry coexists with mutualism in an aphid.

    PubMed

    Salazar, Adrián; Fürstenau, Benjamin; Quero, Carmen; Pérez-Hidalgo, Nicolás; Carazo, Pau; Font, Enrique; Martínez-Torres, David

    2015-01-27

    Understanding the evolutionary transition from interspecific exploitation to cooperation is a major challenge in evolutionary biology. Ant-aphid relationships represent an ideal system to this end because they encompass a coevolutionary continuum of interactions ranging from mutualism to antagonism. In this study, we report an unprecedented interaction along this continuum: aggressive mimicry in aphids. We show that two morphs clonally produced by the aphid Paracletus cimiciformis during its root-dwelling phase establish relationships with ants at opposite sides of the mutualism-antagonism continuum. Although one of these morphs exhibits the conventional trophobiotic (mutualistic) relationship with ants of the genus Tetramorium, aphids of the alternative morph are transported by the ants to their brood chamber and cared for as if they were true ant larvae. Gas chromatography-mass spectrometry analyses reveal that the innate cuticular hydrocarbon profile of the mimic morph resembles the profile of ant larvae more than that of the alternative, genetically identical nonmimic morph. Furthermore, we show that, once in the brood chamber, mimic aphids suck on ant larva hemolymph. These results not only add aphids to the limited list of arthropods known to biosynthesize the cuticular chemicals of their deceived hosts to exploit their resources but describe a remarkable case of plastic aggressive mimicry. The present work adds a previously unidentified dimension to the classical textbook paradigm of aphid-ant relationships by showcasing a complex system at the evolutionary interface between cooperation and exploitation.

  2. Water stress strengthens mutualism among ants, trees, and scale insects.

    PubMed

    Pringle, Elizabeth G; Akçay, Erol; Raab, Ted K; Dirzo, Rodolfo; Gordon, Deborah M

    2013-11-01

    Abiotic environmental variables strongly affect the outcomes of species interactions. For example, mutualistic interactions between species are often stronger when resources are limited. The effect might be indirect: water stress on plants can lead to carbon stress, which could alter carbon-mediated plant mutualisms. In mutualistic ant-plant symbioses, plants host ant colonies that defend them against herbivores. Here we show that the partners' investments in a widespread ant-plant symbiosis increase with water stress across 26 sites along a Mesoamerican precipitation gradient. At lower precipitation levels, Cordia alliodora trees invest more carbon in Azteca ants via phloem-feeding scale insects that provide the ants with sugars, and the ants provide better defense of the carbon-producing leaves. Under water stress, the trees have smaller carbon pools. A model of the carbon trade-offs for the mutualistic partners shows that the observed strategies can arise from the carbon costs of rare but extreme events of herbivory in the rainy season. Thus, water limitation, together with the risk of herbivory, increases the strength of a carbon-based mutualism.

  3. Water Stress Strengthens Mutualism Among Ants, Trees, and Scale Insects

    PubMed Central

    Pringle, Elizabeth G.; Akçay, Erol; Raab, Ted K.; Dirzo, Rodolfo; Gordon, Deborah M.

    2013-01-01

    Abiotic environmental variables strongly affect the outcomes of species interactions. For example, mutualistic interactions between species are often stronger when resources are limited. The effect might be indirect: water stress on plants can lead to carbon stress, which could alter carbon-mediated plant mutualisms. In mutualistic ant–plant symbioses, plants host ant colonies that defend them against herbivores. Here we show that the partners' investments in a widespread ant–plant symbiosis increase with water stress across 26 sites along a Mesoamerican precipitation gradient. At lower precipitation levels, Cordia alliodora trees invest more carbon in Azteca ants via phloem-feeding scale insects that provide the ants with sugars, and the ants provide better defense of the carbon-producing leaves. Under water stress, the trees have smaller carbon pools. A model of the carbon trade-offs for the mutualistic partners shows that the observed strategies can arise from the carbon costs of rare but extreme events of herbivory in the rainy season. Thus, water limitation, together with the risk of herbivory, increases the strength of a carbon-based mutualism. PMID:24223521

  4. Frontotemporal Lobar Degeneration and MicroRNAs

    PubMed Central

    Piscopo, Paola; Albani, Diego; Castellano, Anna E.; Forloni, Gianluigi; Confaloni, Annamaria

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) includes a spectrum of disorders characterized by changes of personality and social behavior and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly microRNAs (miRNAs). Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107, and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD. PMID:26903860

  5. Generalized mutual information of quantum critical chains

    NASA Astrophysics Data System (ADS)

    Alcaraz, F. C.; Rajabpour, M. A.

    2015-04-01

    We study the generalized mutual information I˜n of the ground state of different critical quantum chains. The generalized mutual information definition that we use is based on the well established concept of the Rényi divergence. We calculate this quantity numerically for several distinct quantum chains having either discrete Z (Q ) symmetries (Q -state Potts model with Q =2 ,3 ,4 and Z (Q ) parafermionic models with Q =5 ,6 ,7 ,8 and also Ashkin-Teller model with different anisotropies) or the U (1 ) continuous symmetries (Klein-Gordon field theory, X X Z and spin-1 Fateev-Zamolodchikov quantum chains with different anisotropies). For the spin chains these calculations were done by expressing the ground-state wave functions in two special bases. Our results indicate some general behavior for particular ranges of values of the parameter n that defines I˜n. For a system, with total size L and subsystem sizes ℓ and L -ℓ , the I˜n has a logarithmic leading behavior given by c/˜n4 log[L/π sin(π/ℓ L ) ] where the coefficient c˜n is linearly dependent on the central charge c of the underlying conformal field theory describing the system's critical properties.

  6. Novel microRNA prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation.

    PubMed

    Hu, Shijun; Huang, Mei; Nguyen, Patricia K; Gong, Yongquan; Li, Zongjin; Jia, Fangjun; Lan, Feng; Liu, Junwei; Nag, Divya; Robbins, Robert C; Wu, Joseph C

    2011-09-13

    Although stem cell therapy has provided a promising treatment for myocardial infarction, the low survival of the transplanted cells in the infarcted myocardium is possibly a primary reason for failure of long-term improvement. Therefore, the development of novel prosurvival strategies to boost stem cell survival will be of significant benefit to this field. Cardiac progenitor cells (CPCs) were isolated from transgenic mice, which constitutively express firefly luciferase and green fluorescent protein. The CPCs were transduced with individual lentivirus carrying the precursor of miR-21, miR-24, and miR-221, a cocktail of these 3 microRNA precursors, or green fluorescent protein as a control. After challenge in serum free medium, CPCs treated with the 3 microRNA cocktail showed significantly higher viability compared with untreated CPCs. After intramuscular and intramyocardial injections, in vivo bioluminescence imaging showed that microRNA cocktail-treated CPCs survived significantly longer after transplantation. After left anterior descending artery ligation, microRNA cocktail-treated CPCs boost the therapeutic efficacy in terms of functional recovery. Histological analysis confirmed increased myocardial wall thickness and CPC engraftment in the myocardium with the microRNA cocktail. Finally, we used bioinformatics analysis and experimental validation assays to show that Bim, a critical apoptotic activator, is an important target gene of the microRNA cocktail, which collectively can bind to the 3'UTR region of Bim and suppress its expression. We have demonstrated that a microRNA prosurvival cocktail (miR-21, miR-24, and miR-221) can improve the engraftment of transplanted cardiac progenitor cells and therapeutic efficacy for treatment of ischemic heart disease.

  7. Altered spinal microRNA-146a and the microRNA-183 cluster contribute to osteoarthritic pain in knee joints.

    PubMed

    Li, Xin; Kroin, Jeffrey S; Kc, Ranjan; Gibson, Gary; Chen, Di; Corbett, Grant T; Pahan, Kalipada; Fayyaz, Sana; Kim, Jae-Sung; van Wijnen, Andre J; Suh, Joon; Kim, Su-Gwan; Im, Hee-Jeong

    2013-12-01

    The objective of this study was to examine whether altered expression of microRNAs in central nervous system components is pathologically linked to chronic knee joint pain in osteoarthritis. A surgical animal model for knee joint OA was generated by medial meniscus transection in rats followed by behavioral pain tests. Relationships between pathological changes in knee joint and development of chronic joint pain were examined by histology and imaging analyses. Alterations in microRNAs associated with OA-evoked pain sensation were determined in bilateral lumbar dorsal root ganglia (DRG) and the spinal dorsal horn by microRNA array followed by individual microRNA analyses. Gain- and loss-of-function studies of selected microRNAs (miR-146a and miR-183 cluster) were conducted to identify target pain mediators regulated by these selective microRNAs in glial cells. The ipsilateral hind leg displayed significantly increased hyperalgesia after 4 weeks of surgery, and sensitivity was sustained for the remainder of the 8-week experimental period (F = 341, p < 0.001). The development of OA-induced chronic pain was correlated with pathological changes in the knee joints as assessed by histological and imaging analyses. MicroRNA analyses showed that miR-146a and the miR-183 cluster were markedly reduced in the sensory neurons in DRG (L4/L5) and spinal cord from animals experiencing knee joint OA pain. The downregulation of miR-146a and/or the miR-183 cluster in the central compartments (DRG and spinal cord) are closely associated with the upregulation of inflammatory pain mediators. The corroboration between decreases in these signature microRNAs and their specific target pain mediators were further confirmed by gain- and loss-of-function analyses in glia, the major cellular component of the central nervous system (CNS). MicroRNA therapy using miR-146a and the miR-183 cluster could be powerful therapeutic intervention for OA in alleviating joint pain and concomitantly

  8. Altered Spinal MicroRNA-146a and the MicroRNA-183 Cluster Contribute to Osteoarthritic Pain in Knee Joints

    PubMed Central

    Li, Xin; Kroin, Jeffrey S; Kc, Ranjan; Gibson, Gary; Chen, Di; Corbett, Grant T; Pahan, Kalipada; Fayyaz, Sana; Kim, Jae-Sung; van Wijnen, Andre J.; Suh, Joon; Kim, Su-Gwan; Im, Hee-Jeong

    2015-01-01

    Objective Examine whether altered expression of microRNAs in central nervous system components is pathologically linked to chronic knee joint pain in osteoarthritis. Methods A surgical animal model for knee joint OA was generated by medial meniscus transection in rats followed by behavioral pain tests. Relationships between pathological changes in knee joint and development of chronic joint pain were examined by histology and imaging analyses. Alterations in microRNAs associated with OA-evoked pain sensation were determined in bilateral lumbar dorsal root ganglia (DRG) and the spinal dorsal horn by microRNA array followed by individual microRNA analyses. Gain- and loss-of-function studies of selected microRNAs (miR-146a and miR-183 cluster) were conducted to identify target pain mediators regulated by these selective microRNAs in glial cells. Results The ipsilateral hind leg displayed significantly increased hyperalgesia after 4 weeks of surgery and sensitivity was sustained for the remainder of the 8 week experimental period (F=341, P<0.001). The development of OA-induced chronic pain was correlated with pathological changes in the knee joints as assessed by histological and imaging analyses. MicroRNA analyses showed that miR-146a and the miR-183 cluster were markedly reduced in the sensory neurons in DRG (L4/L5) and spinal cord from animals experiencing knee joint OA pain. The downregulation of miR-146a and/or the miR-183 cluster in the central compartments (DRG and spinal cord) are closely associated with the upregulation of inflammatory pain mediators. The corroboration between decreases in these signature microRNAs and their specific target pain mediators were further confirmed by gain- and loss-of-function analyses in glia, the major cellular component of the central nervous system (CNS). Conclusion MicroRNA therapy using miR-146a and the miR-183 cluster could be powerful therapeutic intervention for OA in alleviating joint pain and concomitantly regenerating

  9. Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles.

    PubMed

    Zhang, Yu-Jun; Hu, Ying; Li, Jing; Chi, Yu-Jing; Jiang, Wei-Wei; Zhang, Feng; Liu, Yu-Lan

    2017-02-01

    The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD). We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4+ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly de-regulated in CD4+ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR-206-3p, miR-181a-5p, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.

  10. Reward value comparison via mutual inhibition in ventromedial prefrontal cortex

    PubMed Central

    Strait, Caleb E.; Blanchard, Tommy C.; Hayden, Benjamin Y.

    2014-01-01

    Recent theories suggest that reward-based choice reflects competition between value signals in the ventromedial prefrontal cortex (vmPFC). We tested this idea by recording vmPFC neurons while macaques performed a gambling task with asynchronous offer presentation. We found that neuronal activity shows four patterns consistent with selection via mutual inhibition. (1) Correlated tuning for probability and reward size, suggesting that vmPFC carries an integrated value signal, (2) anti-correlated tuning curves for the two options, suggesting mutual inhibition, (3) neurons rapidly come to signal the value of the chosen offer, suggesting the circuit serves to produce a choice, (4) after regressing out the effects of option values, firing rates still could predict choice – a choice probability signal. In addition, neurons signaled gamble outcomes, suggesting that vmPFC contributes to both monitoring and choice processes. These data suggest a possible mechanism for reward-based choice and endorse the centrality of vmPFC in that process. PMID:24881835

  11. Lotus hosts delimit the mutualism-parasitism continuum of Bradyrhizobium.

    PubMed

    Regus, J U; Gano, K A; Hollowell, A C; Sofish, V; Sachs, J L

    2015-02-01

    Symbioses are modelled as evolutionarily and ecologically variable with fitness outcomes for hosts shifting on a continuum from mutualism to parasitism. In a classic example, rhizobia fix atmospheric nitrogen for legume hosts in exchange for photosynthetic carbon. Rhizobial infection often enhances legume growth, but hosts also incur interaction costs because of root tissues and or metabolites needed to support symbionts in planta. Rhizobia exhibit genetic variation in symbiotic effectiveness, and ecological changes in light or mineral nitrogen availability can also alter the benefits of rhizobial infection for hosts. The net effects of symbiosis thus can range from mutualistic to parasitic in a context-dependent manner. We tested the extent of the mutualism-parasitism continuum in the legume-rhizobium symbiosis and the degree to which host investment can shape its limits. We infected Lotus strigosus with sympatric Bradyrhizobium genotypes that vary in symbiotic effectiveness. Inoculations occurred under different mineral nitrogen and light regimes spanning ecologically relevant ranges. Net growth benefits of Bradyrhizobium infection varied for Lotus and were reduced or eliminated dependent on Bradyrhizobium genotype, mineral nitrogen and light availability. But we did not detect parasitism. Lotus proportionally reduced investment in Bradyrhizobium as net benefit from infection decreased. Lotus control occurred primarily after infection, via fine-scale modulation of nodule growth, as opposed to control over initial nodulation. Our results show how divestment of symbiosis by Lotus can prevent shifts to parasitism.

  12. Sufficient dimension reduction via squared-loss mutual information estimation.

    PubMed

    Suzuki, Taiji; Sugiyama, Masashi

    2013-03-01

    The goal of sufficient dimension reduction in supervised learning is to find the low-dimensional subspace of input features that contains all of the information about the output values that the input features possess. In this letter, we propose a novel sufficient dimension-reduction method using a squared-loss variant of mutual information as a dependency measure. We apply a density-ratio estimator for approximating squared-loss mutual information that is formulated as a minimum contrast estimator on parametric or nonparametric models. Since cross-validation is available for choosing an appropriate model, our method does not require any prespecified structure on the underlying distributions. We elucidate the asymptotic bias of our estimator on parametric models and the asymptotic convergence rate on nonparametric models. The convergence analysis utilizes the uniform tail-bound of a U-process, and the convergence rate is characterized by the bracketing entropy of the model. We then develop a natural gradient algorithm on the Grassmann manifold for sufficient subspace search. The analytic formula of our estimator allows us to compute the gradient efficiently. Numerical experiments show that the proposed method compares favorably with existing dimension-reduction approaches on artificial and benchmark data sets.

  13. Permutation auto-mutual information of electroencephalogram in anesthesia

    NASA Astrophysics Data System (ADS)

    Liang, Zhenhu; Wang, Yinghua; Ouyang, Gaoxiang; Voss, Logan J.; Sleigh, Jamie W.; Li, Xiaoli

    2013-04-01

    Objective. The dynamic change of brain activity in anesthesia is an interesting topic for clinical doctors and drug designers. To explore the dynamical features of brain activity in anesthesia, a permutation auto-mutual information (PAMI) method is proposed to measure the information coupling of electroencephalogram (EEG) time series obtained in anesthesia. Approach. The PAMI is developed and applied on EEG data collected from 19 patients under sevoflurane anesthesia. The results are compared with the traditional auto-mutual information (AMI), SynchFastSlow (SFS, derived from the BIS index), permutation entropy (PE), composite PE (CPE), response entropy (RE) and state entropy (SE). Performance of all indices is assessed by pharmacokinetic/pharmacodynamic (PK/PD) modeling and prediction probability. Main results. The PK/PD modeling and prediction probability analysis show that the PAMI index correlates closely with the anesthetic effect. The coefficient of determination R2 between PAMI values and the sevoflurane effect site concentrations, and the prediction probability Pk are higher in comparison with other indices. The information coupling in EEG series can be applied to indicate the effect of the anesthetic drug sevoflurane on the brain activity as well as other indices. The PAMI of the EEG signals is suggested as a new index to track drug concentration change. Significance. The PAMI is a useful index for analyzing the EEG dynamics during general anesthesia.

  14. Reward value comparison via mutual inhibition in ventromedial prefrontal cortex.

    PubMed

    Strait, Caleb E; Blanchard, Tommy C; Hayden, Benjamin Y

    2014-06-18

    Recent theories suggest that reward-based choice reflects competition between value signals in the ventromedial prefrontal cortex (vmPFC). We tested this idea by recording vmPFC neurons while macaques performed a gambling task with asynchronous offer presentation. We found that neuronal activity shows four patterns consistent with selection via mutual inhibition: (1) correlated tuning for probability and reward size, suggesting that vmPFC carries an integrated value signal; (2) anti-correlated tuning curves for the two options, suggesting mutual inhibition; (3) neurons rapidly come to signal the value of the chosen offer, suggesting the circuit serves to produce a choice; and (4) after regressing out the effects of option values, firing rates still could predict choice-a choice probability signal. In addition, neurons signaled gamble outcomes, suggesting that vmPFC contributes to both monitoring and choice processes. These data suggest a possible mechanism for reward-based choice and endorse the centrality of vmPFC in that process. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Mutual information model for link prediction in heterogeneous complex networks

    PubMed Central

    Shakibian, Hadi; Moghadam Charkari, Nasrollah

    2017-01-01

    Recently, a number of meta-path based similarity indices like PathSim, HeteSim, and random walk have been proposed for link prediction in heterogeneous complex networks. However, these indices suffer from two major drawbacks. Firstly, they are primarily dependent on the connectivity degrees of node pairs without considering the further information provided by the given meta-path. Secondly, most of them are required to use a single and usually symmetric meta-path in advance. Hence, employing a set of different meta-paths is not straightforward. To tackle with these problems, we propose a mutual information model for link prediction in heterogeneous complex networks. The proposed model, called as Meta-path based Mutual Information Index (MMI), introduces meta-path based link entropy to estimate the link likelihood and could be carried on a set of available meta-paths. This estimation measures the amount of information through the paths instead of measuring the amount of connectivity between the node pairs. The experimental results on a Bibliography network show that the MMI obtains high prediction accuracy compared with other popular similarity indices. PMID:28344326

  16. Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif

    NASA Astrophysics Data System (ADS)

    Hamilton, Mark P.; Rajapakshe, Kimal; Hartig, Sean M.; Reva, Boris; McLellan, Michael D.; Kandoth, Cyriac; Ding, Li; Zack, Travis I.; Gunaratne, Preethi H.; Wheeler, David A.; Coarfa, Cristian; McGuire, Sean E.

    2013-11-01

    MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA ‘superfamily’ consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFβ and p53 pathways by the miR-17-19-130 superfamily members.

  17. Profiling Pre-MicroRNA and Mature MicroRNA Expressions Using a Single Microarray and Avoiding Separate Sample Preparation

    PubMed Central

    Gan, Lin; Denecke, Bernd

    2013-01-01

    Mature microRNA is a crucial component in the gene expression regulation network. At the same time, microRNA gene expression and procession is regulated in a precise and collaborated way. Pre-microRNAs mediate products during the microRNA transcription process, they can provide hints of microRNA gene expression regulation or can serve as alternative biomarkers. To date, little effort has been devoted to pre-microRNA expression profiling. In this study, three human and three mouse microRNA profile data sets, based on the Affymetrix miRNA 2.0 array, have been re-analyzed for both mature and pre-microRNA signals as a primary test of parallel mature/pre-microRNA expression profiling on a single platform. The results not only demonstrated a glimpse of pre-microRNA expression in human and mouse, but also the relationship of microRNA expressions between pre- and mature forms. The study also showed a possible application of currently available microRNA microarrays in profiling pre-microRNA expression in a time and cost effective manner. PMID:27605179

  18. Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

    PubMed

    Tarek, Marwa; Louka, Manal Louis; Khairy, Eman; Ali-Labib, Randa; Zakaria Zaky, Doaa; Montasser, Iman F

    2017-05-01

    There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

  19. Profiling of microRNAs in AML cells following overexpression or silencing of the VEGF gene

    PubMed Central

    Li, Li; Zhu, Lixia; Wang, Yungui; Zhou, De; Zhu, Jingjing; Xie, Wanzhuo; Ye, Xiujin

    2017-01-01

    Acute myeloid leukemia (AML) is a disease of the hematopoietic progenitor cells associated with heterogeneous clonal proliferation. Vascular endothelial growth factor (VEGF) and its receptors play important roles in the regulation of angiogenesis during physiological and pathological processes. It is thought that AML cells have an autocrine VEGF pathway that contributes to the development and progression of AML. In addition, growing evidence has suggested that numerous microRNAs are involved in AML. The present study aimed to investigate the relationship between VEGF dysregulation and microRNA profiles in AML cells and patients. VEGF-overexpressing and VEGF-knockdown leukemia cells were constructed and changes in the patterns of microRNA expression were analyzed using a microRNA array. Subsequently, mononuclear cells from the blood of patients with AML showing high or low expression levels of VEGF were obtained and were used to assess the patterns of microRNA expression by reverse transcription-quantitative polymerase chain reaction. The results of the present study suggested that downregulation of VEGF markedly altered the profile of microRNAs in AML cells, while upregulation of VEGF did not. Examination of clinical samples from patients with AML showed that several microRNAs were closely associated with the expression level of VEGF, including miR-20a, miR-93, miR-16-5p, miR-17-5p, miR-124-5p and miR-17-3p. These results suggested that VEGF may be a pivotal protein that can both receive and initiate signals in leukemia cells. PMID:28123529

  20. Profiling of microRNAs in AML cells following overexpression or silencing of the VEGF gene.

    PubMed

    Li, Li; Zhu, Lixia; Wang, Yungui; Zhou, De; Zhu, Jingjing; Xie, Wanzhuo; Ye, Xiujin

    2017-01-01

    Acute myeloid leukemia (AML) is a disease of the hematopoietic progenitor cells associated with heterogeneous clonal proliferation. Vascular endothelial growth factor (VEGF) and its receptors play important roles in the regulation of angiogenesis during physiological and pathological processes. It is thought that AML cells have an autocrine VEGF pathway that contributes to the development and progression of AML. In addition, growing evidence has suggested that numerous microRNAs are involved in AML. The present study aimed to investigate the relationship between VEGF dysregulation and microRNA profiles in AML cells and patients. VEGF-overexpressing and VEGF-knockdown leukemia cells were constructed and changes in the patterns of microRNA expression were analyzed using a microRNA array. Subsequently, mononuclear cells from the blood of patients with AML showing high or low expression levels of VEGF were obtained and were used to assess the patterns of microRNA expression by reverse transcription-quantitative polymerase chain reaction. The results of the present study suggested that downregulation of VEGF markedly altered the profile of microRNAs in AML cells, while upregulation of VEGF did not. Examination of clinical samples from patients with AML showed that several microRNAs were closely associated with the expression level of VEGF, including miR-20a, miR-93, miR-16-5p, miR-17-5p, miR-124-5p and miR-17-3p. These results suggested that VEGF may be a pivotal protein that can both receive and initiate signals in leukemia cells.

  1. MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation

    PubMed Central

    Pigazzi, Martina; Manara, Elena; Bresolin, Silvia; Tregnago, Claudia; Beghin, Alessandra; Baron, Emma; Giarin, Emanuela; Cho, Er-Chieh; Masetti, Riccardo; Rao, Dinesh S.; Sakamoto, Kathleen M.; Basso, Giuseppe

    2013-01-01

    MicroRNA-34b down-regulation in acute myeloid leukemia was previously shown to induce CREB overexpression, thereby causing leukemia proliferation in vitro and in vivo. The role of microRNA-34b and CREB in patients with myeloid malignancies has never been evaluated. We examined microRNA-34b expression and the methylation status of its promoter in cells from patients diagnosed with myeloid malignancies. We used gene expression profiling to identify signatures of myeloid transformation. We established that microRNA-34b has suppressor ability and that CREB has oncogenic potential in primary bone marrow cell cultures and in vivo. MicroRNA-34b was found to be up-regulated in pediatric patients with juvenile myelomonocytic leukemia (n=17) and myelodysplastic syndromes (n=28), but was down-regulated in acute myeloid leukemia patients at diagnosis (n=112). Our results showed that hypermethylation of the microRNA-34b promoter occurred in 66% of cases of acute myeloid leukemia explaining the low microRNA-34b levels and CREB overexpression, whereas preleukemic myelodysplastic syndromes and juvenile myelomonocytic leukemia were not associated with hypermethylation or CREB overexpression. In paired samples taken from the same patients when they had myelodysplastic syndrome and again during the subsequent acute myeloid leukemia, we confirmed microRNA-34b promoter hypermethylation at leukemia onset, with 103 CREB target genes differentially expressed between the two disease stages. This subset of CREB targets was confirmed to associate with high-risk myelodysplastic syndromes in a separate cohort of patients (n=20). Seventy-eight of these 103 CREB targets were also differentially expressed between healthy samples (n=11) and de novo acute myeloid leukemia (n=72). Further, low microRNA-34b and high CREB expression levels induced aberrant myelopoiesis through CREB-dependent pathways in vitro and in vivo. In conclusion, we suggest that microRNA-34b controls CREB expression and

  2. Coevolution and divergence in the Joshua tree/yucca moth mutualism.

    PubMed

    Godsoe, William; Yoder, Jeremy B; Smith, Christopher Irwin; Pellmyr, Olle

    2008-06-01

    Theory suggests that coevolution drives diversification in obligate pollination mutualism, but it has been difficult to disentangle the effects of coevolution from other factors. We test the hypothesis that differential selection by two sister species of pollinating yucca moths (Tegeticula spp.) drove divergence between two varieties of the Joshua tree (Yucca brevifolia) by comparing measures of differentiation in floral and vegetative features. We show that floral features associated with pollination evolved more rapidly than vegetative features extrinsic to the interaction and that a key floral feature involved in the mutualism is more differentiated than any other and matches equivalent differences in the morphology of the pollinating moths. A phylogenetically based, ancestral states reconstruction shows that differences in moth morphology arose in the time since they first became associated with Joshua trees. These results suggest that coevolution, rather than extrinsic environmental factors, has driven divergence in this obligate pollination mutualism.

  3. MicroRNA Inhibitors as Anticancer Therapies

    DTIC Science & Technology

    2007-08-17

    therapeutic approach. We are currently testing these approaches. 15. SUBJECT TERMS microRNA , miRNA , oncomir, E2F, cancer 16. SECURITY...of the microRNAs within this cluster is a therapeutic approach for the treatment of breast cancer . We undertook several strategies to test this...8 Appendices……………………………………………………………………………11 4 Introduction MicroRNAs ( miRNAs ) are short, noncoding RNAs

  4. A microRNA family exerts maternal control on sex determination in C. elegans.

    PubMed

    McJunkin, Katherine; Ambros, Victor

    2017-02-15

    Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidated a major biological role of the nematode mir-35 family of maternally contributed essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream of and downstream from her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from the mir-35 family in this process, suppressor-26 (sup-26) and NHL (NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (nhl-2), encode RNA-binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of Caenorhabditis elegans Repression of nhl-2 by the mir-35 family is required for not only proper sex determination but also viability, showing that a single microRNA target site can be essential. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-naïve; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves naïveté and prevents premature deleterious developmental decisions.

  5. A microRNA family exerts maternal control on sex determination in C. elegans

    PubMed Central

    McJunkin, Katherine; Ambros, Victor

    2017-01-01

    Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidated a major biological role of the nematode mir-35 family of maternally contributed essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream of and downstream from her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from the mir-35 family in this process, suppressor-26 (sup-26) and NHL (NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (nhl-2), encode RNA-binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of Caenorhabditis elegans. Repression of nhl-2 by the mir-35 family is required for not only proper sex determination but also viability, showing that a single microRNA target site can be essential. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-naïve; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves naïveté and prevents premature deleterious developmental decisions. PMID:28279983

  6. Graph embedded nonparametric mutual information for supervised dimensionality reduction.

    PubMed

    Bouzas, Dimitrios; Arvanitopoulos, Nikolaos; Tefas, Anastasios

    2015-05-01

    In this paper, we propose a novel algorithm for dimensionality reduction that uses as a criterion the mutual information (MI) between the transformed data and their corresponding class labels. The MI is a powerful criterion that can be used as a proxy to the Bayes error rate. Furthermore, recent quadratic nonparametric implementations of MI are computationally efficient and do not require any prior assumptions about the class densities. We show that the quadratic nonparametric MI can be formulated as a kernel objective in the graph embedding framework. Moreover, we propose its linear equivalent as a novel linear dimensionality reduction algorithm. The derived methods are compared against the state-of-the-art dimensionality reduction algorithms with various classifiers and on various benchmark and real-life datasets. The experimental results show that nonparametric MI as an optimization objective for dimensionality reduction gives comparable and in most of the cases better results compared with other dimensionality reduction methods.

  7. Influence of inhomogeneities on holographic mutual information and butterfly effect

    NASA Astrophysics Data System (ADS)

    Cai, Rong-Gen; Zeng, Xiao-Xiong; Zhang, Hai-Qing

    2017-07-01

    We study the effect of inhomogeneity, which is induced by the graviton mass in massive gravity, on the mutual information and the chaotic behavior of a 2+1-dimensional field theory from the gauge/gravity duality. When the system is near-homogeneous, the mutual information increases as the graviton mass grows. However, when the system is far from homogeneity, the mutual information decreases as the graviton mass increases. By adding the perturbations of energy into the system, we investigate the dynamical mutual information in the shock wave geometry. We find that the greater perturbations disrupt the mutual information more rapidly, which resembles the butterfly effect in chaos theory. Besides, the greater inhomogeneity reduces the dynamical mutual information more quickly just as in the static case.

  8. Functional traits determine formation of mutualism and predation interactions in seed-rodent dispersal system of a subtropical forest

    NASA Astrophysics Data System (ADS)

    Chang, Gang; Zhang, Zhibin

    2014-02-01

    Network structure in plant-animal systems has been widely investigated but the roles of functional traits of plants and animals in formation of mutualism and predation interactions and community structure are still not fully understood. In this study, we quantitatively assessed interaction strength of mutualism and predation between 5 tree species and 7 rodent species by using semi-natural enclosures in a subtropical forest in southwest China. Seeds with high handling-time and nutrition traits (for both rat and mouse species) or high tannin trait (for mouse species) show high mutualism but low predation with rodents; while seeds with low handling-time and low nutrition traits show high predation but low mutualism with rodents. Large-sized rat species are more linked to seeds with high handling-time and high nutrition traits, while small-sized mouse species are more connected with seeds with low handling-time, low nutrition value and high tannin traits. Anti-predation seed traits tend to increase chance of mutualism instead of reducing predation by rodents, suggesting formation of mutualism may be connected with that of predation. Our study demonstrates that seed and animal traits play significant roles in the formation of mutualism and predation and network structure of the seed-rodent dispersal system.

  9. Mutually-antagonistic interactions in baseball networks

    NASA Astrophysics Data System (ADS)

    Saavedra, Serguei; Powers, Scott; McCotter, Trent; Porter, Mason A.; Mucha, Peter J.

    2010-03-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.

  10. Mutually unbiased bases and bound entanglement

    NASA Astrophysics Data System (ADS)

    Hiesmayr, Beatrix C.; Löffler, Wolfgang

    2014-04-01

    In this contribution we relate two different key concepts: mutually unbiased bases (MUBs) and entanglement. We provide a general toolbox for analyzing and comparing entanglement of quantum states for different dimensions and numbers of particles. In particular we focus on bound entanglement, i.e. highly mixed states which cannot be distilled by local operations and classical communications. For a certain class of states—for which the state-space forms a ‘magic’ simplex—we analyze the set of bound entangled states detected by the MUB criterion for different dimensions d and number of particles n. We find that the geometry is similar for different d and n, consequently the MUB criterion opens possibilities to investigate the typicality of positivity under partial transposition (PPT)-bound and multipartite bound entanglement more deeply and provides a simple experimentally feasible tool to detect bound entanglement.

  11. Concurrent behavior: Are the interpretations mutually exclusive?

    PubMed Central

    Lyon, David O.

    1982-01-01

    The experimental literature is replete with examples of behavior which occur concurrently with a schedule of reinforcement. These concurrent behaviors, often with similar topographies and occurring under like circumstances, may be interpreted as functionally autonomous, collateral, adjunctive, superstitious or mediating behavior. The degree to which the interaction of concurrent and schedule controlled behavior is used in the interpretation of behavior illustrated the importance of distinguishing among these interpretations by experimental procedure. The present paper reviews the characteristics of these interpretations, and discusses the experimental procedures necessary to distinguish among them. The paper concludes that the interpretations are mutually exclusive and refer to distinct behaviors, but that the distinction between any two of the interpretations requires more than one experimental procedure. PMID:22478568

  12. MicroRNA Regulation of Epithelial to Mesenchymal Transition

    PubMed Central

    Abba, Mohammed L.; Patil, Nitin; Leupold, Jörg Hendrik; Allgayer, Heike

    2016-01-01

    Epithelial to mesenchymal transition (EMT) is a central regulatory program that is similar in many aspects to several steps of embryonic morphogenesis. In addition to its physiological role in tissue repair and wound healing, EMT contributes to chemo resistance, metastatic dissemination and fibrosis, amongst others. Classically, the morphological change from epithelial to mesenchymal phenotype is characterized by the appearance or loss of a group of proteins which have come to be recognized as markers of the EMT process. As with all proteins, these molecules are controlled at the transcriptional and translational level by transcription factors and microRNAs, respectively. A group of developmental transcription factors form the backbone of the EMT cascade and a large body of evidence shows that microRNAs are heavily involved in the successful coordination of mesenchymal transformation and vice versa, either by suppressing the expression of different groups of transcription factors, or otherwise acting as their functional mediators in orchestrating EMT. This article dissects the contribution of microRNAs to EMT and analyzes the molecular basis for their roles in this cellular process. Here, we emphasize their interaction with core transcription factors like the zinc finger enhancer (E)-box binding homeobox (ZEB), Snail and Twist families as well as some pluripotency transcription factors. PMID:26784241

  13. Transcriptome dynamics of the microRNA inhibition response

    PubMed Central

    Wen, Jiayu; Leucci, Elenora; Vendramin, Roberto; Kauppinen, Sakari; Lund, Anders H.; Krogh, Anders; Parker, Brian J.

    2015-01-01

    We report a high-resolution time series study of transcriptome dynamics following antimiR-mediated inhibition of miR-9 in a Hodgkin lymphoma cell-line—the first such dynamic study of the microRNA inhibition response—revealing both general and specific aspects of the physiological response. We show miR-9 inhibition inducing a multiphasic transcriptome response, with a direct target perturbation before 4 h, earlier than previously reported, amplified by a downstream peak at ∼32 h consistent with an indirect response due to secondary coherent regulation. Predictive modelling indicates a major role for miR-9 in post-transcriptional control of RNA processing and RNA binding protein regulation. Cluster analysis identifies multiple co-regulated gene regulatory modules. Functionally, we observe a shift over time from mRNA processing at early time points to translation at later time points. We validate the key observations with independent time series qPCR and we experimentally validate key predicted miR-9 targets. Methodologically, we developed sensitive functional data analytic predictive methods to analyse the weak response inherent in microRNA inhibition experiments. The methods of this study will be applicable to similar high-resolution time series transcriptome analyses and provides the context for more accurate experimental design and interpretation of future microRNA inhibition studies. PMID:26089393

  14. Invasional meltdown: invader-invader mutualism facilitates a secondary invasion.

    PubMed

    Green, Peter T; O'Dowd, Dennis J; Abbott, Kirsti L; Jeffery, Mick; Retallick, Kent; Mac Nally, Ralph

    2011-09-01

    In multiply invaded ecosystems, introduced species should interact with each other as well as with native species. Invader-invader interactions may affect the success of further invaders by altering attributes of recipient communities and propagule pressure. The invasional meltdown hypothesis (IMH) posits that positive interactions among invaders initiate positive population-level feedback that intensifies impacts and promotes secondary invasions. IMH remains controversial: few studies show feedback between invaders that amplifies their effects, and none yet demonstrate facilitation of entry and spread of secondary invaders. Our results show that supercolonies of an alien ant, promoted by mutualism with introduced honeydew-secreting scale insects, permitted invasion by an exotic land snail on Christmas Island, Indian Ocean. Modeling of land snail spread over 750 sites across 135 km2 over seven years showed that the probability of land snail invasion was facilitated 253-fold in ant supercolonies but impeded in intact forest where predaceous native land crabs remained abundant. Land snail occurrence at neighboring sites, a measure of propagule pressure, also promoted land snail spread. Site comparisons and experiments revealed that ant supercolonies, by killing land crabs but not land snails, disrupted biotic resistance and provided enemy-free space. Predation pressure on land snails was lower (28.6%), survival 115 times longer, and abundance 20-fold greater in supercolonies than in intact forest. Whole-ecosystem suppression of supercolonies reversed the probability of land snail invasion by allowing recolonization of land crabs; land snails were much less likely (0.79%) to invade sites where supercolonies were suppressed than where they remained intact. Our results provide strong empirical evidence for IMH by demonstrating that mutualism between invaders reconfigures key interactions in the recipient community. This facilitates entry of secondary invaders and

  15. MicroRNA-124 slows down the progression of Huntington's disease by promoting neurogenesis in the striatum.

    PubMed

    Liu, Tian; Im, Wooseok; Mook-Jung, Inhee; Kim, Manho

    2015-05-01

    MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington's disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington's disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Huntington's disease transgenic mouse in the rotarod test. 5-Bromo-2'-deoxyuridine (BrdU) staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was decreased. These findings suggest that microRNA-124 slows down the progression of Huntington's disease possibly through its important role in neuronal differentiation and survival.

  16. Stage-Specific MicroRNAs and Their Role in the Anticancer Effects of Calorie Restriction in a Rat Model of ER-Positive Luminal Breast Cancer

    PubMed Central

    Devlin, Kaylyn L.; Sanford, Tiffany; Harrison, Lauren M.; LeBourgeois, Paul; Lashinger, Laura M.; Mambo, Elizabeth; Hursting, Stephen D.

    2016-01-01

    MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized. We used the dimethylbenz[a]-anthracene-induced model of luminal mammary cancer in Sprague Dawley rats to elucidate which microRNAs are linked to progression in this type of cancer and, subsequently, to study how calorie restriction affects such microRNAs. We identified eight microRNAs (miR-10a, miR-10b, miR-21, miR-124, miR-125b, miR-126, miR-145 and miR-200a) to be associated with DMBA-induced mammary tumor progression. Calorie restriction, which greatly increased tumor-free survival and decreased the overall size of tumors that did develop, significantly decreased the expression of one microRNA, miR-200a, which was positively associated with tumor progression. We further showed that inhibition of miR-200a function, mimicking the effect of calorie restriction on this microRNA, inhibited proliferation in both rat (LA7) and human (MCF7) luminal mammary cancer cell lines. These findings present, for the first time, a stage-specific profile of microRNAs in a rodent model of luminal mammary cancer. Furthermore, we have identified the regulation of miR-200a, a microRNA that is positively associated with progression in this model, as a possible mechanism contributing to the anticancer effects of calorie restriction. PMID:27433802

  17. Stage-Specific MicroRNAs and Their Role in the Anticancer Effects of Calorie Restriction in a Rat Model of ER-Positive Luminal Breast Cancer.

    PubMed

    Devlin, Kaylyn L; Sanford, Tiffany; Harrison, Lauren M; LeBourgeois, Paul; Lashinger, Laura M; Mambo, Elizabeth; Hursting, Stephen D

    2016-01-01

    MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized. We used the dimethylbenz[a]-anthracene-induced model of luminal mammary cancer in Sprague Dawley rats to elucidate which microRNAs are linked to progression in this type of cancer and, subsequently, to study how calorie restriction affects such microRNAs. We identified eight microRNAs (miR-10a, miR-10b, miR-21, miR-124, miR-125b, miR-126, miR-145 and miR-200a) to be associated with DMBA-induced mammary tumor progression. Calorie restriction, which greatly increased tumor-free survival and decreased the overall size of tumors that did develop, significantly decreased the expression of one microRNA, miR-200a, which was positively associated with tumor progression. We further showed that inhibition of miR-200a function, mimicking the effect of calorie restriction on this microRNA, inhibited proliferation in both rat (LA7) and human (MCF7) luminal mammary cancer cell lines. These findings present, for the first time, a stage-specific profile of microRNAs in a rodent model of luminal mammary cancer. Furthermore, we have identified the regulation of miR-200a, a microRNA that is positively associated with progression in this model, as a possible mechanism contributing to the anticancer effects of calorie restriction.

  18. MicroRNA network changes in the brain stem underlie the development of hypertension.

    PubMed

    DeCicco, Danielle; Zhu, Haisun; Brureau, Anthony; Schwaber, James S; Vadigepalli, Rajanikanth

    2015-09-01

    Hypertension is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 well-annotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage- and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.

  19. Hypoxia-Related MicroRNA-210 Is a Diagnostic Marker for Discriminating Osteoblastoma and Osteosarcoma

    PubMed Central

    Riester, Scott M.; Torres-Mora, Jorge; Dudakovic, Amel; Camilleri, Emily T.; Wang, Wei; Xu, Fuhua; Thaler, Roman R.; Evans, Jared M.; Zwartbol, René; Briaire-de Bruijn, Inge H.; Maran, Avudaiappan; Folpe, Andrew L.; Inwards, Carrie Y.; Rose, Peter S.; Shives, Thomas C.; Yaszemski, Michael J.; Sim, Franklin H.; Deyle, David R.; Larson, Annalise N.; Galindo, Mario A.; Cleven, Arjen G. H.; Oliveira, Andre M.; Cleton-Jansen, Anne-Marie; Bovée, Judith V. M. G.; van Wijnen, Andre J.

    2017-01-01

    Osteoblastoma is a benign bone tumor that can often be difficult to distinguish from malignant osteosarcoma. Because misdiagnosis can result in unfavorable clinical outcomes, we have investigated microRNAs as potential diagnostic biomarkers for distinguishing between these two tumor types. Next generation RNA sequencing was used as an expression screen to evaluate >2,000 microRNAs present in tissue derived from rare formalin fixed paraffin embedded (FFPE) archival tumor specimens. MicroRNAs displaying the greatest ability to discriminate between these two tumors were validated on an independent tumor set, using qPCR assays. Initial screening by RNA-seq identified four microRNA biomarker candidates. Expression of three miRNAs (miR-451a, miR-144-3p, miR-486-5p) was higher in osteoblastoma, while the miR-210 was elevated in osteosarcoma. Validation of these microRNAs on an independent data set of 22 tumor specimens by qPCR revealed that miR-210 is the most discriminating marker. This microRNA displays low levels of expression across all of the osteoblastoma specimens and robust expression in the majority of the osteosarcoma specimens. Application of these biomarkers to a clinical test case showed that these microRNA biomarkers permit re-classification of a misdiagnosed FFPE tumor sample from osteoblastoma to osteosarcoma. Our findings establish that the hypoxia-related miR-210 is a discriminatory marker that distinguishes between osteoblastoma and osteosarcoma. This discovery provides a complementary molecular approach to support pathological classification of two diagnostically challenging musculoskeletal tumors. Because miR-210 is linked to the cellular hypoxia response, its detection may be linked to well-established pro-angiogenic and metastatic roles of hypoxia in osteosarcomas and other tumor cell types. PMID:27324965

  20. Systematic analysis of the regulatory functions of microRNAs in chicken hepatic lipid metabolism

    PubMed Central

    Li, Hong; Ma, Zheng; Jia, Lijuan; Li, Yanmin; Xu, Chunlin; Wang, Taian; Han, Ruili; Jiang, Ruirui; Li, Zhuanjian; Sun, Guirong; Kang, Xiangtao; Liu, Xiaojun

    2016-01-01

    Laying performance is an important economic trait in hens, and this physiological process is largely influenced by the liver function. The livers of hens at 20- and 30-week-old stages were investigated using the next generation sequencing to identify the differences of microRNA expression profiles. Compared with the 20-week-old hens, 67 down- and 13 up-regulated microRNAs were verified to be significant differentially expressed (false discovery rate, FDR ≤ 0.05) (SDE) in the 30-week-old. We also identified 13 down- and 6 up-regulated novel differentially expressed (DE) microRNAs. miR-22-3p and miR-146b-5p, which exhibit critical roles in mammalian lipid metabolism, showed the most abundant expression and the highest fold-change, respectively. A total of 648 potential target genes of the SDE microRNAs were identified through an integrated analysis of microRNAs and the DE genes obtained in previous RNA-sequencing, including FADS1, FADS2, ELOVL6 and ACSL5, which are critical lipid metabolism-related regulators. Bioinformatic analyses revealed that target genes were mainly enriched in lipid-related metabolism processes. This work provides the first study of the expression patterns of hepatic microRNAs between 20- and 30-week old hens. The findings may serve as a fundamental resource for understanding the detailed functions of microRNAs in the molecular regulatory systems of lipid metabolism. PMID:27535581

  1. On the Mutual Coupling Between Circular Resonant Slots

    NASA Technical Reports Server (NTRS)

    Abou-Khousa, M. A.; Kharkovsky, S.; Zoughi, R.

    2007-01-01

    For near- and far-field microwave imaging purposes, array of circular resonant slots can be utilized to sample the electric field at a given reference plane. In general, the sensitivity of such array probes is impaired by the mutual coupling present between the radiating elements. The mutual coupling problem poses a design tradeoff between the resolution of the array and its sensitivity. In this paper, we investigate the mutual coupling between circular resonant slots in conducting ground plane both numerically and experimentally. Based on the analysis of the dominant coupling mechanism, i.e., the surface currents, various remedies to reduce the slots' mutual coupling are proposed and verified.

  2. On the Mutual Coupling between Circular Resonant Slots

    NASA Technical Reports Server (NTRS)

    Abou-Khousa, M. A.; Kharkovshy, S.; Zoughi, R.

    2007-01-01

    For near- and far-field microwave imaging purposes, array of circular resonant slots can be utilized to sample the electric field at a given reference plane. In general, the sensitivity of such an array is impaired by the existing mutual coupling between the radiating elements or in this case circular slots. The mutual coupling problem imposes a design tradeoff between the resolution of the array and the overall system sensitivity and dynamic range. In this paper, the mutual coupling between circular resonant slots in conducting ground plane is investigated both numerically and experimentally. In particular, the mutual coupling in the E- and H-plane configurations of two identical slots is studied.

  3. Bad guys turned nice? A critical assessment of Wolbachia mutualisms in arthropod hosts.

    PubMed

    Zug, Roman; Hammerstein, Peter

    2015-02-01

    Wolbachia are the most abundant bacterial endosymbionts among arthropods. Although maternally inherited, they do not conform to the widespread view that vertical transmission inevitably selects for beneficial symbionts. Instead, Wolbachia are notorious for their reproductive parasitism which, although lowering host fitness, ensures their spread. However, even for reproductive parasites it can pay to enhance host fitness. Indeed, there is a recent upsurge of reports on Wolbachia-associated fitness benefits. Therefore, the question arises how such instances of mutualism are related to the phenotypes of reproductive parasitism. Here, we review the evidence of Wolbachia mutualisms in arthropods, including both facultative and obligate relationships, and critically assess their biological relevance. Although many studies report anti-pathogenic effects of Wolbachia, few actually prove these effects to be relevant to field conditions. We further show that Wolbachia frequently have beneficial and detrimental effects at the same time, and that reproductive manipulations and obligate mutualisms may share common mechanisms. These findings undermine the idea of a clear-cut distinction between Wolbachia mutualism and parasitism. In general, both facultative and obligate mutualisms can have a strong, and sometimes unforeseen, impact on the ecology and evolution of Wolbachia and their arthropod hosts. Acknowledging this mutualistic potential might be the key to a better understanding of some unresolved issues in the study of Wolbachia-host interactions.

  4. Astrometry of mutual approximations between natural satellites. Application to the Galilean moons

    NASA Astrophysics Data System (ADS)

    Morgado, B.; Assafin, M.; Vieira-Martins, R.; Camargo, J. I. B.; Dias-Oliveira, A.; Gomes-Júnior, A. R.

    2016-08-01

    Typically we can deliver astrometric positions of natural satellites with errors in the 50-150 mas range. Apparent distances from mutual phenomena, have much smaller errors, less than 10 mas. However, this method can only be applied during the equinox of the planets. We developed a method that can provide accurate astrometric data for natural satellites - the mutual approximations. The method can be applied when any two satellites pass close by each other in the apparent sky plane. The fundamental parameter is the central instant t0 of the passage when the distances reach a minimum. We applied the method for the Galilean moons. All observations were made with a 0.6 m telescope with a narrow-band filter centred at 889 nm with width of 15 nm which attenuated Jupiter's scattered light. We obtained central instants for 14 mutual approximations observed in 2014-2015. We determined t0 with an average precision of 3.42 mas (10.43 km). For comparison, we also applied the method for 5 occultations in the 2009 mutual phenomena campaign and for 22 occultations in the 2014-2015 campaign. The comparisons of t0 determined by our method with the results from mutual phenomena show an agreement by less than 1σ error in t0, typically less than 10 mas. This new method is particularly suitable for observations by small telescopes.

  5. Nectar bacteria, but not yeast, weaken a plant-pollinator mutualism.

    PubMed

    Vannette, Rachel L; Gauthier, Marie-Pierre L; Fukami, Tadashi

    2013-02-07

    Mutualistic interactions are often subject to exploitation by species that are not directly involved in the mutualism. Understanding which organisms act as such 'third-party' species and how they do so is a major challenge in the current study of mutualistic interactions. Here, we show that even species that appear ecologically similar can have contrasting effects as third-party species. We experimentally compared the effects of nectar-inhabiting bacteria and yeasts on the strength of a mutualism between a hummingbird-pollinated shrub, Mimulus aurantiacus, and its pollinators. We found that the common bacterium Gluconobacter sp., but not the common yeast Metschnikowia reukaufii, reduced pollination success, seed set and nectar consumption by pollinators, thereby weakening the plant-pollinator mutualism. We also found that the bacteria reduced nectar pH and total sugar concentration more greatly than the yeasts did and that the bacteria decreased glucose concentration and increased fructose concentration whereas the yeasts affected neither. These distinct changes to nectar chemistry may underlie the microbes' contrasting effects on the mutualism. Our results suggest that it is necessary to understand the determinants of microbial species composition in nectar and their differential modification of floral rewards to explain the mutual benefits that plants and pollinators gain from each other.

  6. Nectar bacteria, but not yeast, weaken a plant–pollinator mutualism

    PubMed Central

    Vannette, Rachel L.; Gauthier, Marie-Pierre L.; Fukami, Tadashi

    2013-01-01

    Mutualistic interactions are often subject to exploitation by species that are not directly involved in the mutualism. Understanding which organisms act as such ‘third-party’ species and how they do so is a major challenge in the current study of mutualistic interactions. Here, we show that even species that appear ecologically similar can have contrasting effects as third-party species. We experimentally compared the effects of nectar-inhabiting bacteria and yeasts on the strength of a mutualism between a hummingbird-pollinated shrub, Mimulus aurantiacus, and its pollinators. We found that the common bacterium Gluconobacter sp., but not the common yeast Metschnikowia reukaufii, reduced pollination success, seed set and nectar consumption by pollinators, thereby weakening the plant–pollinator mutualism. We also found that the bacteria reduced nectar pH and total sugar concentration more greatly than the yeasts did and that the bacteria decreased glucose concentration and increased fructose concentration whereas the yeasts affected neither. These distinct changes to nectar chemistry may underlie the microbes' contrasting effects on the mutualism. Our results suggest that it is necessary to understand the determinants of microbial species composition in nectar and their differential modification of floral rewards to explain the mutual benefits that plants and pollinators gain from each other. PMID:23222453

  7. Competing RNA secondary structures are required for mutually exclusive splicing of the Dscam exon 6 cluster.

    PubMed

    May, Gemma E; Olson, Sara; McManus, C Joel; Graveley, Brenton R

    2011-02-01

    Alternative splicing of eukaryotic pre-mRNAs is an important mechanism for generating proteome diversity and regulating gene expression. The Drosophila melanogaster Down Syndrome Cell Adhesion Molecule (Dscam) gene is an extreme example of mutually exclusive splicing. Dscam contains 95 alternatively spliced exons that potentially encode 38,016 distinct mRNA and protein isoforms. We previously identified two sets of conserved sequence elements, the docking site and selector sequences in the Dscam exon 6 cluster, which contains 48 mutually exclusive exons. These elements were proposed to engage in competing RNA secondary structures required for mutually exclusive splicing, though this model has not yet been experimentally tested. Here we describe a new system that allowed us to demonstrate that the docking site and selector sequences are indeed required for exon 6 mutually exclusive splicing and that the strength of these RNA structures determines the frequency of exon 6 inclusion. We also show that the function of the docking site has been conserved for ~500 million years of evolution. This work demonstrates that conserved intronic sequences play a functional role in mutually exclusive splicing of the Dscam exon 6 cluster.

  8. Gap junctions modulate glioma invasion by direct transfer of microRNA

    PubMed Central

    Hong, Xiaoting; Sin, Wun Chey; Harris, Andrew L.; Naus, Christian C.

    2015-01-01

    The invasiveness of high-grade glioma is the primary reason for poor survival following treatment. Interaction between glioma cells and surrounding astrocytes are crucial to invasion. We investigated the role of gap junction mediated miRNA transfer in this context. By manipulating gap junctions with a gap junction inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that functional glioma-glioma gap junctions suppress glioma invasion while glioma-astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions are permeable to microRNA, we compared the microRNA profiles of astrocytes before and after co-culture with glioma cells, identifying specific microRNAs as candidates for transfer through gap junctions from glioma cells to astrocytes. Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes is through gap junctions; this transfer is responsible, in part, for the pro-invasive effect. Our results establish a role for glioma-astrocyte gap junction mediated microRNA signaling in modulation of glioma invasive behavior, and that gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our findings reveal the potential for therapeutic interventions based on abolishing alteration of stromal cells by tumor cells via manipulation of microRNA and gap junction channel activity. PMID:25978028

  9. Gap junctions modulate glioma invasion by direct transfer of microRNA.

    PubMed

    Hong, Xiaoting; Sin, Wun Chey; Harris, Andrew L; Naus, Christian C

    2015-06-20

    The invasiveness of high-grade glioma is the primary reason for poor survival following treatment. Interaction between glioma cells and surrounding astrocytes are crucial to invasion. We investigated the role of gap junction mediated miRNA transfer in this context. By manipulating gap junctions with a gap junction inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that functional glioma-glioma gap junctions suppress glioma invasion while glioma-astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions are permeable to microRNA, we compared the microRNA profiles of astrocytes before and after co-culture with glioma cells, identifying specific microRNAs as candidates for transfer through gap junctions from glioma cells to astrocytes. Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes is through gap junctions; this transfer is responsible, in part, for the pro-invasive effect. Our results establish a role for glioma-astrocyte gap junction mediated microRNA signaling in modulation of glioma invasive behavior, and that gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our findings reveal the potential for therapeutic interventions based on abolishing alteration of stromal cells by tumor cells via manipulation of microRNA and gap junction channel activity.

  10. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression.

    PubMed

    Diederichs, Sven; Haber, Daniel A

    2007-12-14

    MicroRNAs are small endogenous noncoding RNAs involved in posttranscriptional gene regulation. During microRNA biogenesis, Drosha and Dicer process the primary transcript (pri-miRNA) through a precursor hairpin (pre-miRNA) to the mature miRNA. The miRNA is incorporated into the RNA-Induced Silencing Complex (RISC) with Argonaute proteins, the effector molecules in RNA interference (RNAi). Here, we show that all Argonautes elevate mature miRNA expression posttranscriptionally, independent of RNase activity. Also, we identify a role for the RISC slicer Argonaute2 (Ago2) in cleaving the pre-miRNA to an additional processing intermediate, termed Ago2-cleaved precursor miRNA or ac-pre-miRNA. This endogenous, on-pathway intermediate results from cleavage of the pre-miRNA hairpin 12 nucleotides from its 3'-end. By analogy to siRNA processing, Ago2 cleavage may facilitate removal of the nicked passenger strand from RISC after maturation. The multiple roles of Argonautes in the RNAi effector phase and miRNA biogenesis and maturation suggest coordinate regulation of microRNA expression and function.

  11. MicroRNA and Breast Cancer Progression

    DTIC Science & Technology

    2007-08-01

    AD_________________ Award Number: W81XWH-05-1-0428 TITLE: MicroRNA and Breast Cancer Progression...3. DATES COVERED (From - To) 15 JUL 2005 - 14 JUL 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER MicroRNA and Breast Cancer Progression 5b...We hypothesized that certain miRNA species are differentially expressed in the normal breast epithelium and breast cancer cells. Our concept was that

  12. Rényi mutual information for a free scalar field in even dimensions

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Long, Jiang

    2017-08-01

    We compute the Rényi mutual information of two disjoint spheres in free massless scalar theory in even dimensions higher than 2. The spherical twist operator in a conformal field theory can be expanded into the sum of local primary operators and their descendants. We analyze the primary operators in the replicated scalar theory and find the ones of the fewest dimensions and spins. We study the one-point function of these operators in the conical geometry and obtain their expansion coefficients in the operator product expansion of spherical twist operators. We show that the Rényi mutual information can be expressed in terms of the conformal partial waves. We compute explicitly the Rényi mutual information up to order zd, where z is the cross ratio and d is the spacetime dimension.

  13. Model, properties and imputation method of missing SNP genotype data utilizing mutual information

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Wan, Weiming; Wang, Rui-Sheng; Feng, Enmin

    2009-07-01

    Mutual information can be used as a measure for the association of a genetic marker or a combination of markers with the phenotype. In this paper, we study the imputation of missing genotype data. We first utilize joint mutual information to compute the dependence between SNP sites, then construct a mathematical model in order to find the two SNP sites having maximal dependence with missing SNP sites, and further study the properties of this model. Finally, an extension method to haplotype-based imputation is proposed to impute the missing values in genotype data. To verify our method, extensive experiments have been performed, and numerical results show that our method is superior to haplotype-based imputation methods. At the same time, numerical results also prove joint mutual information can better measure the dependence between SNP sites. According to experimental results, we also conclude that the dependence between the adjacent SNP sites is not necessarily strongest.

  14. Design of a compact optical see-through head-worn display with mutual occlusion capability

    NASA Astrophysics Data System (ADS)

    Cakmakci, Ozan; Ha, Yonggang; Rolland, Jannick

    2005-08-01

    We present the first-order design details and preliminary lens design and performance analysis of a compact optical system that can achieve mutual occlusions. Mutual occlusion is the ability of real objects to occlude virtual objects and virtual objects to occlude real objects. Mutual occlusion is a desirable attribute for a certain class of augmented reality applications where realistic overlays based on the depth cue is important. Compactness is achieved through the use of polarization optics. First order layout of the system is similar to that of a Keplerian telescope operating at finite conjugates. Additionally, we require the image to lie on the plane of the object with unit magnification. We show that the same lens can be used as the objective and the eyepiece. The system is capable of having very close to zero distortion.

  15. Reservoir computing with a slowly modulated mask signal for preprocessing using a mutually coupled optoelectronic system

    NASA Astrophysics Data System (ADS)

    Tezuka, Miwa; Kanno, Kazutaka; Bunsen, Masatoshi

    2016-08-01

    Reservoir computing is a machine-learning paradigm based on information processing in the human brain. We numerically demonstrate reservoir computing with a slowly modulated mask signal for preprocessing by using a mutually coupled optoelectronic system. The performance of our system is quantitatively evaluated by a chaotic time series prediction task. Our system can produce comparable performance with reservoir computing with a single feedback system and a fast modulated mask signal. We showed that it is possible to slow down the modulation speed of the mask signal by using the mutually coupled system in reservoir computing.

  16. Plant-fungus mutualism affects spider composition in successional fields.

    PubMed

    Finkes, Laura K; Cady, Alan B; Mulroy, Juliana C; Clay, Keith; Rudgers, Jennifer A

    2006-03-01

    Mutualistic symbionts are widespread in plants and may have strong, bottom-up influences on community structure. Here we show that a grass-endophyte mutualism shifts the composition of a generalist predator assemblage. In replicated, successional fields we manipulated endophyte infection by Neotyphodium coenophialum in a dominant, non-native plant (Lolium arundinaceum). We compared the magnitude of the endophyte effect with manipulations of thatch biomass, a habitat feature of known importance to spiders. The richness of both spider families and morphospecies was greater in the absence of the endophyte, although total spider abundance was not affected. Thatch removal reduced both spider abundance and richness, and endophyte and thatch effects were largely additive. Spider families differed in responses, with declines in Linyphiidae and Thomisidae due to the endophyte and declines in Lycosidae due to thatch removal. Results demonstrate that the community impacts of non-native plants can depend on plants' mutualistic associates, such as fungal endophytes.

  17. Galois-unitary operators that cycle mutually-unbiased bases

    NASA Astrophysics Data System (ADS)

    Dang, Hoan; Appleby, Marcus; Bengtsson, Ingemar

    2015-03-01

    Wigner's theorem states that probability-preserving transformations of quantum states must be either unitary or anti-unitary. However, if we restrict ourselves to a subspace of a Hilbert space, it is possible to generalize the notion of anti-unitaries. Such transformations were recently constructed in search of Symmetric Informationally-Complete (SIC) states. They are called Galois-unitaries (g-unitaries for short), as they are unitaries composed with Galois automorphisms of a chosen number field extension. Despite certain bizarre behaviors of theirs, we show that g-unitaries are indeed useful in the theory of Mutually-Unbiased Bases (MUBs), as they help solve the MUB-cycling problem and provide a construction of MUB-balanced states. HD was supported by the Natural Sciences and Engineering Research Council of Canada and the Vanier Canada Graduate Scholarship

  18. Evolutionary dynamics with fluctuating population sizes and strong mutualism

    NASA Astrophysics Data System (ADS)

    Chotibut, Thiparat; Nelson, David R.

    2015-08-01

    Game theory ideas provide a useful framework for studying evolutionary dynamics in a well-mixed environment. This approach, however, typically enforces a strictly fixed overall population size, deemphasizing natural growth processes. We study a competitive Lotka-Volterra model, with number fluctuations, that accounts for natural population growth and encompasses interaction scenarios typical of evolutionary games. We show that, in an appropriate limit, the model describes standard evolutionary games with both genetic drift and overall population size fluctuations. However, there are also regimes where a varying population size can strongly influence the evolutionary dynamics. We focus on the strong mutualism scenario and demonstrate that standard evolutionary game theory fails to describe our simulation results. We then analytically and numerically determine fixation probabilities as well as mean fixation times using matched asymptotic expansions, taking into account the population size degree of freedom. These results elucidate the interplay between population dynamics and evolutionary dynamics in well-mixed systems.

  19. Extending the scope of holographic mutual information and chaotic behavior

    NASA Astrophysics Data System (ADS)

    Sircar, Nilanjan; Sonnenschein, Jacob; Tangarife, Walter

    2016-05-01

    We extend the use of holography to investigate the scrambling properties of various physical systems. Specifically, we consider: (i) non-conformal backgrounds of black Dp branes, (ii) asymptotically Lifshitz black holes, and (iii) black AdS solutions of Gauss-Bonnet gravity. We use the disruption of the entanglement entropy as a probe of the chaotic features of such systems. Our analysis shows that these theories share the same type of behavior as conformal theories as they undergo chaos; however, in the case of Gauss-Bonnet gravity, we find a stark difference in the evolution of the mutual information for negative Gauss-Bonnet coupling. This may signal an inconsistency of the latter.

  20. Modeling mutual feedback between users and recommender systems

    NASA Astrophysics Data System (ADS)

    Zeng, An; Yeung, Chi Ho; Medo, Matúš; Zhang, Yi-Cheng

    2015-07-01

    Recommender systems daily influence our decisions on the Internet. While considerable attention has been given to issues such as recommendation accuracy and user privacy, the long-term mutual feedback between a recommender system and the decisions of its users has been neglected so far. We propose here a model of network evolution which allows us to study the complex dynamics induced by this feedback, including the hysteresis effect which is typical for systems with non-linear dynamics. Despite the popular belief that recommendation helps users to discover new things, we find that the long-term use of recommendation can contribute to the rise of extremely popular items and thus ultimately narrow the user choice. These results are supported by measurements of the time evolution of item popularity inequality in real systems. We show that this adverse effect of recommendation can be tamed by sacrificing part of short-term recommendation accuracy.

  1. Mutual coupling effects in antenna arrays, volume 1

    NASA Technical Reports Server (NTRS)

    Collin, R. E.

    1986-01-01

    Mutual coupling between rectangular apertures in a finite antenna array, in an infinite ground plane, is analyzed using the vector potential approach. The method of moments is used to solve the equations that result from setting the tangential magnetic fields across each aperture equal. The approximation uses a set of vector potential model functions to solve for equivalent magnetic currents. A computer program was written to carry out this analysis and the resulting currents were used to determine the co- and cross-polarized far zone radiation patterns. Numerical results for various arrays using several modes in the approximation are presented. Results for one and two aperture arrays are compared against published data to check on the agreement of this model with previous work. Computer derived results are also compared against experimental results to test the accuracy of the model. These tests of the accuracy of the program showed that it yields valid data.

  2. Wireless power transmission applied the mutual coupling between coils

    NASA Astrophysics Data System (ADS)

    Furuta, Kenta; Baba, Ryouichi; Shun, Endo; Nunokawa, Kazuki; Takahashi, Wataru; Maruyama, Tamami

    2017-07-01

    Recently, the studies of wireless power transfer (WPT) to electric vehicles in motion on the snow-piled road have been reported. In WPT by magnetic field resonance method, transmission coefficient S21, which is one of the scattering parameters, from transmission coil to received coil are degraded because of misalignment of transmitting and receiving coil, the distance between these coils, and the effects of the ice and snow. This paper adopts parasitic coil as a solution to improve the reception power in which the parasitic coil is inserted between transmitting and receiving coils. Analysis and experimental results show that parasitic coil could improve the value of S21 by 15 dB using mutual coupling. LED could be light by this solution when the distance between transmitting and receiving coils are 150 mm.

  3. Synaptic microRNAs Coordinately Regulate Synaptic mRNAs: Perturbation by Chronic Alcohol Consumption.

    PubMed

    Most, Dana; Leiter, Courtney; Blednov, Yuri A; Harris, R Adron; Mayfield, R Dayne

    2016-01-01

    Local translation of mRNAs in the synapse has a major role in synaptic structure and function. Chronic alcohol use causes persistent changes in synaptic mRNA expression, possibly mediated by microRNAs localized in the synapse. We profiled the transcriptome of synaptoneurosomes (SN) obtained from the amygdala of mice that consumed 20% ethanol (alcohol) in a 30-day continuous two-bottle choice test to identify the microRNAs that target alcohol-induced mRNAs. SN are membrane vesicles containing pre- and post-synaptic compartments of neurons and astroglia and are a unique model for studying the synaptic transcriptome. We previously showed that chronic alcohol regulates mRNA expression in a coordinated manner. Here, we examine microRNAs and mRNAs from the same samples to define alcohol-responsive synaptic microRNAs and their predicted interactions with targeted mRNAs. The aim of the study was to identify the microRNA-mRNA synaptic interactions that are altered by alcohol. This was accomplished by comparing the effect of alcohol in SN and total homogenate preparations from the same samples. We used a combination of unbiased bioinformatic methods (differential expression, correlation, co-expression, microRNA-mRNA target prediction, co-targeting, and cell type-specific analyses) to identify key alcohol-sensitive microRNAs. Prediction analysis showed that a subset of alcohol-responsive microRNAs was predicted to target many alcohol-responsive mRNAs, providing a bidirectional analysis for identifying microRNA-mRNA interactions. We found microRNAs and mRNAs with overlapping patterns of expression that correlated with alcohol consumption. Cell type-specific analysis revealed that a significant number of alcohol-responsive mRNAs and microRNAs were unique to glutamate neurons and were predicted to target each other. Chronic alcohol consumption appears to perturb the coordinated microRNA regulation of mRNAs in SN, a mechanism that may explain the aberrations in synaptic

  4. Synaptic microRNAs Coordinately Regulate Synaptic mRNAs: Perturbation by Chronic Alcohol Consumption

    PubMed Central

    Most, Dana; Leiter, Courtney; Blednov, Yuri A; Harris, R Adron; Mayfield, R Dayne

    2016-01-01

    Local translation of mRNAs in the synapse has a major role in synaptic structure and function. Chronic alcohol use causes persistent changes in synaptic mRNA expression, possibly mediated by microRNAs localized in the synapse. We profiled the transcriptome of synaptoneurosomes (SN) obtained from the amygdala of mice that consumed 20% ethanol (alcohol) in a 30-day continuous two-bottle choice test to identify the microRNAs that target alcohol-induced mRNAs. SN are membrane vesicles containing pre- and post-synaptic compartments of neurons and astroglia and are a unique model for studying the synaptic transcriptome. We previously showed that chronic alcohol regulates mRNA expression in a coordinated manner. Here, we examine microRNAs and mRNAs from the same samples to define alcohol-responsive synaptic microRNAs and their predicted interactions with targeted mRNAs. The aim of the study was to identify the microRNA–mRNA synaptic interactions that are altered by alcohol. This was accomplished by comparing the effect of alcohol in SN and total homogenate preparations from the same samples. We used a combination of unbiased bioinformatic methods (differential expression, correlation, co-expression, microRNA-mRNA target prediction, co-targeting, and cell type-specific analyses) to identify key alcohol-sensitive microRNAs. Prediction analysis showed that a subset of alcohol-responsive microRNAs was predicted to target many alcohol-responsive mRNAs, providing a bidirectional analysis for identifying microRNA–mRNA interactions. We found microRNAs and mRNAs with overlapping patterns of expression that correlated with alcohol consumption. Cell type-specific analysis revealed that a significant number of alcohol-responsive mRNAs and microRNAs were unique to glutamate neurons and were predicted to target each other. Chronic alcohol consumption appears to perturb the coordinated microRNA regulation of mRNAs in SN, a mechanism that may explain the aberrations in synaptic

  5. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer.

    PubMed

    Huo, Lei; Wang, Yan; Gong, Yun; Krishnamurthy, Savitri; Wang, Jing; Diao, Lixia; Liu, Chang-Gong; Liu, Xiuping; Lin, Feng; Symmans, William F; Wei, Wei; Zhang, Xinna; Sun, Li; Alvarez, Ricardo H; Ueno, Naoto T; Fouad, Tamer M; Harano, Kenichi; Debeb, Bisrat G; Wu, Yun; Reuben, James; Cristofanilli, Massimo; Zuo, Zhuang

    2016-04-01

    Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situ hybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.

  6. Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process.

    PubMed

    Alanazi, Ibrahim O; Ebrahimie, Esmaeil

    2016-07-01

    Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p < 0.01) with the apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.

  7. Mutual Events in the Uranian satellite system in 2007

    NASA Astrophysics Data System (ADS)

    Arlot, J. E.

    2008-09-01

    observed "pole-on" and the relative inclinations of the orbits of the satellites are very difficult to know. More, this knowledge should allow us to determine the precession of Uranus which is not yet known. Another reason to improve the dynamics of the Uranian satellites is to quantify the dissipation of energy inside the satellites because of the tides: only very accurate astrometric observations may allow to reach such a result. We used two models for our purpose: the one from Laskar and Jacobson (GUST86) based upon observations made using observations made from 1911 to 1986 [1] and the one from Arlot, Lainey and Thuillot (LA06) [2] based upon a different sets of observations made from 1950 to 2006. Astrometric observations Since the mutual events are observable only every 42 years (in fact, 2007 was the first time where mutual events were observed on the Uranian system), many other astrometric observations were performed, mainly with photographic plates, CCD targets or using a meridian transit circle. These observations and their accuracy will be compared with mutual events. Note that these observations introduce some biases in the data (date of the opposition, absolute position of the planet), different than those of mutual events (equinox time). Observations of mutual events in 2007 Due to the difficulty of the observations, very few observations were made: about 15 events were observed using telescopes with apertures from 40 cm to 8 meters... The observing sites which reported observations were Marseille and Pic du Midi (France), Canarian Islands (Spain), La Silla and Paranal (Chile), Itajuba (Brazil), Tubitak (Turkey), Hanle (India) and Siding Spring (Australia). A preliminary analysis Some light curves were reduced and a comparison has been made with the theoretical calculations of the events. A preliminary analysis shows that LA06 has smaller residuals in the longitudes of the satellites than GUST86 but the residuals are equivalent in latitude. This confirms the

  8. MicroRNA-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1)

    PubMed Central

    Zhou, Sijing; Li, Min; Sun, Li; Xu, Xuan; Fei, Guanghe

    2016-01-01

    MicroRNAs are involved in the control of cell growth, and deregulated pulmonary artery smooth muscle cell proliferation plays an essential role in the development of pulmonary hypertension. The objective of this study was to identify differentially expressed microRNA(s) and explore its therapeutic role in treatment of the disease. MicroRNA expression profile analysis showed microRNA-26b was differentially expressed in pulmonary artery smooth muscle cells harvested from monocrotaline-treated rats, and we validated microRNA-26b targets, in vitro and in vivo, CTGF and CCND1, both of which have been shown, in our previous work, to be involved in the pathogenesis of pulmonary hypertension. In vivo experiments demonstrated monocrotaline-induced pulmonary artery remodeling could be almost completely abolished by administration of microRNA-26b, while CTGF or CCND1 shRNA significantly, but only partially, attenuated the remodeling by silencing the designed target. Additionally, exogenous expression of the microRNA-26b substantially downregulated CTGF and CCND1 in human pulmonary artery smooth muscle cells. MicroRNA-26b might be a potent therapeutic tool to treat pulmonary hypertension. PMID:27322082

  9. Microrna-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1).

    PubMed

    Wang, Ran; Ding, Xing; Zhou, Sijing; Li, Min; Sun, Li; Xu, Xuan; Fei, Guanghe

    2016-11-08

    MicroRNAs are involved in the control of cell growth, and deregulated pulmonary artery smooth muscle cell proliferation plays an essential role in the development of pulmonary hypertension. The objective of this study was to identify differentially expressed microRNA(s) and explore its therapeutic role in treatment of the disease. MicroRNA expression profile analysis showed microRNA-26b was differentially expressed in pulmonary artery smooth muscle cells harvested from monocrotaline-treated rats, and we validated microRNA-26b targets, in vitro and in vivo, CTGF and CCND1, both of which have been shown, in our previous work, to be involved in the pathogenesis of pulmonary hypertension. In vivo experiments demonstrated monocrotaline-induced pulmonary artery remodeling could be almost completely abolished by administration of microRNA-26b, while CTGF or CCND1 shRNA significantly, but only partially, attenuated the remodeling by silencing the designed target. Additionally, exogenous expression of the microRNA-26b substantially downregulated CTGF and CCND1 in human pulmonary artery smooth muscle cells. MicroRNA-26b might be a potent therapeutic tool to treat pulmonary hypertension.

  10. Oxidative stress and pro-inflammatory cytokines may act as one of the signals for regulating microRNAs expression in Alzheimer's disease.

    PubMed

    Prasad, Kedar N

    2017-03-01

    Oxidative stress and chronic inflammation are one of the earliest defects that initiate and promote Alzheimer's disease (AD). Studies showed that expressions of microRNAs were upregulated or downregulated in AD. Therefore, these biochemical defects may influence the levels of microRNAs. The up-regulated microRNAs cause neurodegeneration by: (a) decreasing the levels of a nuclear transcriptional factor-2 (Nrf2), (b) reducing the levels of α-secretase ADM10; and (c) reducing the levels of phosphatases. The down-regulated microRNAs cause neurodegeneration by: (a) increasing the levels of β-secretase, (b) increasing the levels of tau kinase; (c) elevating the levels of tau proteins; (d) increasing the levels of APP; and (e) increasing the levels of nuclear factor-kappaB (NF-kB). Antioxidants protect neurons by reducing oxidative stress and chronic inflammation. Therefore, they may also influence the levels of microRNAs. This review briefly describes the studies on changes in the expressions of microRNAs in the pathogenesis of AD. It proposes a hypothesis that free radicals and pro-inflammatory cytokines act as one of the signals that upregulate or downregulate the levels of microRNAs by influencing their transcription, processing or stability leading to neurodegeneration in AD. Antioxidants that reduce oxidative stress and pro-inflammatory cytokines also regulate the levels of microRNAs.

  11. MicroRNAs and atherosclerosis

    PubMed Central

    Madrigal-Matute, Julio; Rotllan, Noemi; Aranda, Juan F.; Fernández-Hernando, Carlos

    2014-01-01

    MicroRNAs (miRNAs) are small (~22nucleotide) sequences of RNA that regulate gene expression at posttranscriptional level. MiRNA/mRNA base pairing complementarity provokes mRNA decay and consequent gene silencing. These endogenous gene expression inhibitors were primarily described in cancer but recent exciting findings have also demonstrated a key role in cardiovascular diseases (CVDs) including atherosclerosis. MiRNAs controls endothelial cell (EC), vascular smooth muscle cell (VSMC) and macrophage functions, and thereby regulate the progression of atherosclerosis. MiRNAs expression is modulated by different stimuli involved in every stage of atherosclerosis and conversely miRNAs modulates several pathways implicated in plaque development such as cholesterol metabolism. In the present review, we focus on the importance of miRNAs in atherosclerosis and we further discuss their potential use as biomarkers and therapeutic targets in CVDs. PMID:23512606

  12. Human MicroRNA Targets

    PubMed Central

    John, Bino; Enright, Anton J; Aravin, Alexei; Tuschl, Thomas; Sander, Chris

    2004-01-01

    MicroRNAs (miRNAs) interact with target mRNAs at specific sites to induce cleavage of the message or inhibit translation. The specific function of most mammalian miRNAs is unknown. We have predicted target sites on the 3′ untranslated regions of human gene transcripts for all currently known 218 mammalian miRNAs to facilitate focused experiments. We report about 2,000 human genes with miRNA target sites conserved in mammals and about 250 human genes conserved as targets between mammals and fish. The prediction algorithm optimizes sequence complementarity using position-specific rules and relies on strict requirements of interspecies conservation. Experimental support for the validity of the method comes from known targets and from strong enrichment of predicted targets in mRNAs associated with the fragile X mental retardation protein in mammals. This is consistent with the hypothesis that miRNAs act as sequence-specific adaptors in the interaction of ribonuclear particles with translationally regulated messages. Overrepresented groups of targets include mRNAs coding for transcription factors, components of the miRNA machinery, and other proteins involved in translational regulation, as well as components of the ubiquitin machinery, representing novel feedback loops in gene regulation. Detailed information about target genes, target processes, and open-source software for target prediction (miRanda) is available at http://www.microrna.org. Our analysis suggests that miRNA genes, which are about 1% of all human genes, regulate protein production for 10% or more of all human genes. PMID:15502875

  13. Reclaiming the Subject Matter as a Guide to Mutual Understanding: Effectiveness and Ethics in Interpersonal Interaction.

    ERIC Educational Resources Information Center

    Deetz, Stanley

    1990-01-01

    Presents H. G. Gadamer's ontology of understanding as a developmental foundation for interpersonal system ethics. Conceptualizes interaction in terms of demand that the subject matter places on openly formed mutual understanding. Shows unethical interactions as practices which prohibit this development. Provides examples of processes by which…

  14. Operational link between mutually unbiased bases and symmetric informationally complete positive operator-valued measures

    NASA Astrophysics Data System (ADS)

    Beneduci, Roberto; Bullock, Thomas J.; Busch, Paul; Carmeli, Claudio; Heinosaari, Teiko; Toigo, Alessandro

    2013-09-01

    We exhibit an operational connection between mutually unbiased bases and symmetric informationally complete positive operator-valued measures. Assuming that the latter exists, we show that there is a strong link between these two structures in all prime power dimensions. We also demonstrate that a similar link cannot exist in dimension 6.

  15. Bichir microRNA repertoire suggests a ray-finned fish affinity of Polypteriforme.

    PubMed

    Yang, Liandong; Zhang, Zhaolei; He, Shunping

    2015-07-25

    The phylogenetic position of Polypteriforme (bichirs) remains elusive, despite extensive research both on morphological and molecular datasets. Unfortunately morphological cladistic analyses and molecular phylogenetic analyses had reached conflicting conclusions, as Polypteriformes were either grouped with lobe-finned fishes (Sarcopterygii) or ray-finned fishes (Actinopterygii), or even classified as their own group, the Brachiopterygii. In this study, we applied a third independent source of datasets, the presence versus absence of microRNAs, to re-investigate the phylogenetic relationship of bichirs. Through deep sequencing of small RNA library, we showed that bichirs should be grouped into ray-finned fishes rather than lobe-finned fishes. Phylogenetic analysis confirmed that bichirs were placed as the most basal member of the ray-finned fishes. Bichirs shared five unique microRNA families with teleostei, which were not found in any other species investigated to date. Bichirs have also retained three of five microRNAs that were previously deemed to be lost exclusively in teleostei. Furthermore, we report more than one hundred novel microRNAs that are unique to bichir. The identification of microRNAs in bichir provides overwhelming evidence for their affinity of ray-finned fishes. The sarcopterygian-like characteristics such as lobed fins, paired ventral lungs, and external gills in juveniles should not be considered as derived traits shared with those of sarcopterygians.

  16. Sequence-based design of bioactive small molecules that target precursor microRNAs.

    PubMed

    Velagapudi, Sai Pradeep; Gallo, Steven M; Disney, Matthew D

    2014-04-01

    Oligonucleotides are designed to target RNA using base pairing rules, but they can be hampered by poor cellular delivery and nonspecific stimulation of the immune system. Small molecules are preferred as lead drugs or probes but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA hairpin precursors, and it identified bioactive small molecules that inhibit biogenesis by binding nuclease-processing sites (44% hit rate). Among 27 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Markedly, microRNA profiling shows that 1 only affects microRNA-96 biogenesis and is at least as selective as an oligonucleotide.

  17. Regulation of tubulin expression by micro-RNAs: implications for drug resistance.

    PubMed

    Lobert, Sharon; Graichen, Mary E

    2013-01-01

    In this chapter, we provide an overview of methods for studying micro-RNA regulation of tubulin isotypes. In clinical studies, β-tubulin isotypes were found to be biomarkers for tumor formation. In addition, because changes in the levels of specific β-tubulin isotypes alter the stability of microtubules in mitotic spindles in vitro, it has been hypothesized that changes in microtubule protein levels could contribute to chemotherapy resistance. Over the past 15 years, micro-RNAs have been shown to target mRNAs in signaling pathways involved in tumor suppression, as well as tumorigenesis. Investigating micro-RNA regulation of tubulin isotypes will shed light on the mechanisms underlying the processes that implicate tubulin isotypes as biomarkers for aggressive tumors or chemotherapy resistance. The methods discussed in this chapter include the use of micro-RNA superarrays, next-generation sequencing, real-time PCR experiments, upregulation of micro-RNAs, and immunoprecipitation of RNA-induced silencing complex. We will show examples of data collected using these methods and how these data contribute to understanding paclitaxel resistance.

  18. 7 CFR 550.13 - Mutuality of interest.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Mutuality of interest. 550.13 Section 550.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT.... Mutual interest exists when both parties benefit in the same qualitative way from the objectives of...

  19. 7 CFR 550.13 - Mutuality of interest.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Mutuality of interest. 550.13 Section 550.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT.... Mutual interest exists when both parties benefit in the same qualitative way from the objectives of...

  20. 7 CFR 550.13 - Mutuality of interest.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Mutuality of interest. 550.13 Section 550.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT.... Mutual interest exists when both parties benefit in the same qualitative way from the objectives of...

  1. 7 CFR 550.13 - Mutuality of interest.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Mutuality of interest. 550.13 Section 550.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT.... Mutual interest exists when both parties benefit in the same qualitative way from the objectives of...

  2. 7 CFR 550.13 - Mutuality of interest.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mutuality of interest. 550.13 Section 550.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT.... Mutual interest exists when both parties benefit in the same qualitative way from the objectives of the...

  3. 76 FR 35084 - Mutual to Stock Conversion Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... Office of Thrift Supervision Mutual to Stock Conversion Application AGENCY: Office of Thrift Supervision... following information collection. Title of Proposal: Mutual to Stock Conversion Application. OMB Number... proposed stock conversion. The purpose of the information collection is to provide OTS with the...

  4. 76 FR 20459 - Mutual to Stock Conversion Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-12

    ... Office of Thrift Supervision Mutual to Stock Conversion Application AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Mutual to Stock Conversion Application. OMB Number: 1550-0014. Form Numbers... furnished in the application in order to determine the safety and soundness of the proposed stock...

  5. Cooperative adaptation to establishment of a synthetic bacterial mutualism.

    PubMed

    Hosoda, Kazufumi; Suzuki, Shingo; Yamauchi, Yoshinori; Shiroguchi, Yasunori; Kashiwagi, Akiko; Ono, Naoaki; Mori, Kotaro; Yomo, Tetsuya

    2011-02-16

    To understand how two organisms that have not previously been in contact can establish mutualism, it is first necessary to examine temporal changes in their phenotypes during the establishment of mutualism. Instead of tracing back the history of known, well-established, natural mutualisms, we experimentally simulated the development of mutualism using two genetically-engineered auxotrophic strains of Escherichia coli, which mimic two organisms that have never met before but later establish mutualism. In the development of this synthetic mutualism, one strain, approximately 10 hours after meeting the partner strain, started oversupplying a metabolite essential for the partner's growth, eventually leading to the successive growth of both strains. This cooperative phenotype adaptively appeared only after encountering the partner strain but before the growth of the strain itself. By transcriptome analysis, we found that the cooperative phenotype of the strain was not accompanied by the local activation of the biosynthesis and transport of the oversupplied metabolite but rather by the global activation of anabolic metabolism. This study demonstrates that an organism has the potential to adapt its phenotype after the first encounter with another organism to establish mutualism before its extinction. As diverse organisms inevitably encounter each other in nature, this potential would play an important role in the establishment of a nascent mutualism in nature.

  6. Mutuality, Self-Silencing, and Disordered Eating in College Women

    ERIC Educational Resources Information Center

    Wechsler, Lisa S.; Riggs, Shelley A.; Stabb, Sally D.; Marshall, David M.

    2006-01-01

    The current study examined patterns of association among mutuality, self-silencing, and disordered eating in an ethnically diverse sample of college women (N = 149). Partner mutuality and overall self-silencing were negatively correlated and together were associated with six disordered eating indices. All four self-silencing subscales were…

  7. 77 FR 73115 - Mutual Savings Association Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ... Office of the Comptroller of the Currency Mutual Savings Association Advisory Committee AGENCY: Office of... has determined that the renewal of the charter of the OCC Mutual Savings Association Advisory... savings associations, the regulatory changes or other steps the OCC may be able to take to ensure the...

  8. Mutuality, Self-Silencing, and Disordered Eating in College Women

    ERIC Educational Resources Information Center

    Wechsler, Lisa S.; Riggs, Shelley A.; Stabb, Sally D.; Marshall, David M.

    2006-01-01

    The current study examined patterns of association among mutuality, self-silencing, and disordered eating in an ethnically diverse sample of college women (N = 149). Partner mutuality and overall self-silencing were negatively correlated and together were associated with six disordered eating indices. All four self-silencing subscales were…

  9. Social Climate Comparison of Mutual Help and Psychotherapy Groups.

    ERIC Educational Resources Information Center

    Toro, Paul A.; Rappaport, Julian

    In recent years, mutual help groups have been formed to address problems in substance abuse, chronic physical illness, mental illness, marital disruption, and child abuse. Despite the proliferation of these groups, little research has been conducted to assess their efficacy or what happens in them. The nature of mutual help groups (N=32) was…

  10. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Applications and Authorizations Special Rules... exclusive applications. Mutually exclusive commercial mobile radio service applications are processed in... 47 Telecommunication 5 2011-10-01 2011-10-01 false Procedures for mutually exclusive...

  11. Higher Education and Foster Grandparent Programs: Exploring Mutual Benefits

    ERIC Educational Resources Information Center

    Peacock, James R.; O'Quin, Jo Ann

    2006-01-01

    The purpose of this article is to highlight ways in which programs within institutions of higher education and Foster Grandparent Programs can interact to their mutual benefit. Given federal and state initiatives to develop linkages between institutions of higher education and community service sites, mutual benefits exist at the program level for…

  12. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Applications and Authorizations Special Rules... exclusive applications. Mutually exclusive commercial mobile radio service applications are processed in... 47 Telecommunication 5 2010-10-01 2010-10-01 false Procedures for mutually exclusive applications...

  13. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Procedures for mutually exclusive applications... filing dates) as acceptable for filing. (4) Window filing group. A window filing group comprises mutually exclusive applications whose filing date is within an announced filing window. An announced filing window...

  14. MicroRNAs as regulatory elements in psoriasis

    PubMed Central

    Liu, Yuan

    2016-01-01

    Abstract Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.

  15. Observation of mutual neutralization in detached plasma

    NASA Astrophysics Data System (ADS)

    Akira, Tonegawa; Isao, Shirota; Ken'ichi, Yoshida; Masataka, Ono; Kazutaka, Kawamura; Tuguhiro, Watanabe; Nobuyoshi, Ohyabu; Hajime, Suzuki; Kazuo, Takayama

    2001-10-01

    Mutual neutralization in collisions between negative ions and positive ions in molecular activated recombination (MAR) has been observed in a high density magnetized sheet plasma source TPDSHEET-IV(Test Plasma produced by Directed current for SHEET plasma) device. Measurements of the negative ion density of hydrogen atom, the electron density, electron temperature, and the heat load to the target plate were carried out in hydrogen high density plasma with hydrogen gas puff. A cylindrical probe made of tungsten ( 0.4 x 2 cm) was used to measure the spatial profiles of H- by a probe-assisted laser photodetachment The Balmer spectra of visible light emission from hydrogen or helium atoms were detected in front of the target plate. A small amount of secondary hydrogen gas puffing into a hydrogen plasma reduced strongly the heat flux to the target and increased rapidly the density of negative ions of hydrogen atom in the circumference of the plasma, while the conventional radiative and three-body recombination processes were disappeared. These results can be well explained by taking the charge exchange recombination of MAR in the detached plasma into account.

  16. Quantum mutual information along unitary orbits

    NASA Astrophysics Data System (ADS)

    Jevtic, Sania; Jennings, David; Rudolph, Terry

    2012-05-01

    Motivated by thermodynamic considerations, we analyze the variation of the quantum mutual information on a unitary orbit of a bipartite system's state with and without global constraints such as energy conservation. We solve the full optimization problem for the smallest system of two qubits and explore thoroughly the effect of unitary operations on the space of reduced-state spectra. We then provide applications of these ideas to physical processes within closed quantum systems such as a generalized collision model approach to thermal equilibrium and a global Maxwell demon playing tricks on local observers. For higher dimensions, the maximization of correlations is relatively straightforward for equal-sized subsystems, however their minimization displays nontrivial structures. We characterize a set of separable states in which the minimally correlated state resides: a collection of classically correlated states admitting a particular “Young tableau” form. Furthermore, a partial order exists on this set with respect to individual marginal entropies, and the presence of a “see-saw effect” for these entropies forces a finer analysis to determine the optimal tableau.

  17. Mutualism between tree shrews and pitcher plants

    PubMed Central

    Moran, Jonathan A; Chin, Lijin

    2010-01-01

    Three species of Nepenthes pitcher plants from Borneo engage in a mutualistic interaction with mountain tree shrews, the basis of which is the exchange of nutritional resources. The plants produce modified “toilet pitchers” that produce copious amounts of exudates, the latter serving as a food source for tree shrews. The exudates are only accessible to the tree shrews when they position their hindquarters over the pitcher orifice. Tree shrews mark valuable resources with feces and regularly defecate into the pitchers when they visit them to feed. Feces represent a valuable source of nitrogen for these Nepenthes species, but there are many facets of the mutualism that are yet to be investigated. These include, but are not limited to, seasonal variation in exudate production rates by the plants, behavioral ecology of visiting tree shrews and the mechanism by which the plants signal to tree shrews that their pitchers represent a food source. Further research into this extraordinary animal-plant interaction is required to gain a better understanding of the benefits to the participating species. PMID:20861680

  18. Genetic drift opposes mutualism during spatial population expansion

    PubMed Central

    Müller, Melanie J. I.; Neugeboren, Beverly I.; Nelson, David R.; Murray, Andrew W.

    2014-01-01

    Mutualistic interactions benefit both partners, promoting coexistence and genetic diversity. Spatial structure can promote cooperation, but spatial expansions may also make it hard for mutualistic partners to stay together, because genetic drift at the expansion front creates regions of low genetic and species diversity. To explore the antagonism between mutualism and genetic drift, we grew cross-feeding strains of the budding yeast Saccharomyces cerevisiae on agar surfaces as a model for mutualists undergoing spatial expansions. By supplying varying amounts of the exchanged nutrients, we tuned strength and symmetry of the mutualistic interaction. Strong mutualism suppresses genetic demixing during spatial expansions and thereby maintains diversity, but weak or asymmetric mutualism is overwhelmed by genetic drift even when mutualism is still beneficial, slowing growth and reducing diversity. Theoretical modeling using experimentally measured parameters predicts the size of demixed regions and how strong mutualism must be to survive a spatial expansion. PMID:24395776

  19. Genetic drift opposes mutualism during spatial population expansion.

    PubMed

    Müller, Melanie J I; Neugeboren, Beverly I; Nelson, David R; Murray, Andrew W

    2014-01-21

    Mutualistic interactions benefit both partners, promoting coexistence and genetic diversity. Spatial structure can promote cooperation, but spatial expansions may also make it hard for mutualistic partners to stay together, because genetic drift at the expansion front creates regions of low genetic and species diversity. To explore the antagonism between mutualism and genetic drift, we grew cross-feeding strains of the budding yeast Saccharomyces cerevisiae on agar surfaces as a model for mutualists undergoing spatial expansions. By supplying varying amounts of the exchanged nutrients, we tuned strength and symmetry of the mutualistic interaction. Strong mutualism suppresses genetic demixing during spatial expansions and thereby maintains diversity, but weak or asymmetric mutualism is overwhelmed by genetic drift even when mutualism is still beneficial, slowing growth and reducing diversity. Theoretical modeling using experimentally measured parameters predicts the size of demixed regions and how strong mutualism must be to survive a spatial expansion.

  20. Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder

    PubMed Central

    Forstner, A J; Hofmann, A; Maaser, A; Sumer, S; Khudayberdiev, S; Mühleisen, T W; Leber, M; Schulze, T G; Strohmaier, J; Degenhardt, F; Treutlein, J; Mattheisen, M; Schumacher, J; Breuer, R; Meier, S; Herms, S; Hoffmann, P; Lacour, A; Witt, S H; Reif, A; Müller-Myhsok, B; Lucae, S; Maier, W; Schwarz, M; Vedder, H; Kammerer-Ciernioch, J; Pfennig, A; Bauer, M; Hautzinger, M; Moebus, S; Priebe, L; Sivalingam, S; Verhaert, A; Schulz, H; Czerski, P M; Hauser, J; Lissowska, J; Szeszenia-Dabrowska, N; Brennan, P; McKay, J D; Wright, A; Mitchell, P B; Fullerton, J M; Schofield, P R; Montgomery, G W; Medland, S E; Gordon, S D; Martin, N G; Krasnov, V; Chuchalin, A; Babadjanova, G; Pantelejeva, G; Abramova, L I; Tiganov, A S; Polonikov, A; Khusnutdinova, E; Alda, M; Cruceanu, C; Rouleau, G A; Turecki, G; Laprise, C; Rivas, F; Mayoral, F; Kogevinas, M; Grigoroiu-Serbanescu, M; Propping, P; Becker, T; Rietschel, M; Cichon, S; Schratt, G; Nöthen, M M

    2015-01-01

    Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD. PMID:26556287

  1. Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder.

    PubMed

    Forstner, A J; Hofmann, A; Maaser, A; Sumer, S; Khudayberdiev, S; Mühleisen, T W; Leber, M; Schulze, T G; Strohmaier, J; Degenhardt, F; Treutlein, J; Mattheisen, M; Schumacher, J; Breuer, R; Meier, S; Herms, S; Hoffmann, P; Lacour, A; Witt, S H; Reif, A; Müller-Myhsok, B; Lucae, S; Maier, W; Schwarz, M; Vedder, H; Kammerer-Ciernioch, J; Pfennig, A; Bauer, M; Hautzinger, M; Moebus, S; Priebe, L; Sivalingam, S; Verhaert, A; Schulz, H; Czerski, P M; Hauser, J; Lissowska, J; Szeszenia-Dabrowska, N; Brennan, P; McKay, J D; Wright, A; Mitchell, P B; Fullerton, J M; Schofield, P R; Montgomery, G W; Medland, S E; Gordon, S D; Martin, N G; Krasnov, V; Chuchalin, A; Babadjanova, G; Pantelejeva, G; Abramova, L I; Tiganov, A S; Polonikov, A; Khusnutdinova, E; Alda, M; Cruceanu, C; Rouleau, G A; Turecki, G; Laprise, C; Rivas, F; Mayoral, F; Kogevinas, M; Grigoroiu-Serbanescu, M; Propping, P; Becker, T; Rietschel, M; Cichon, S; Schratt, G; Nöthen, M M

    2015-11-10

    Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

  2. Acute Pyelonephritis in Renal Allografts–A New Role for MicroRNAs?

    PubMed Central

    Oghumu, Steve; Bracewell, Anna; Nori, Uday; Maclean, Kirsteen H.; Balada-Lasat, Joan-Miquel; Brodsky, Sergey; Pelletier, Ronald; Henry, Mitchell; Satoskar, Abhay R.; Nadasdy, Tibor; Satoskar, Anjali A.

    2014-01-01

    Background Acute pyelonephritis (APN) versus acute rejection (AR) is a frequently encountered diagnostic and therapeutic dilemma in kidney transplants. Variable culture results, overlapping histologic features, and persistent graft dysfunction despite antibiotics are frequently encountered. Therefore, we explored the utility of intragraft microRNA profiles to distinguish between allograft APN and AR. Materials and Methods Between 2003 and 2011, we identified 49 patients with biopsy features of APN, within the first 2 years posttransplant. MicroRNA profiling was performed on 20 biopsies (normal kidney, n=4; unequivocal AR, n=5; features of APN, n=11). Results Only 32% (16/49) of the patients had concomitant positive urine cultures at biopsy, and in 8 of 16 patients, colony count was less than 105 CFU/mL. In 14 of 49 patients, positive urine culture did not coincide with the biopsy, and in 19 of 49 patients, urine cultures were negative. On microRNA profiling, good clustering was seen among the normal kidneys and among AR biopsies. Among the 11 biopsies with features of APN, 4 biopsies showed good clustering with a pattern distinct from AR; (these patients recovered graft function with antibiotics); 7 of 11 biopsies showed heterogeneity in microRNA profiles and variable outcomes with antibiotic treatment. We identified a panel of 25 microRNAs showing statistical difference in expression between AR and APN. MiR-99b, miR-23b let-7b-5p, miR-30a, and miR-145 were validated using qPCR. Conclusion Allograft pyelonephritis can be a diagnostic and therapeutic challenge. A gestalt approach is required. In addition to histology and cultures, differential intragraft microRNA expression may prove helpful to distinguish APN from AR in renal allograft biopsies. PMID:24521778

  3. Strategy diversity stabilizes mutualism through investment cycles, phase polymorphism, and spatial bubbles.

    PubMed

    Boza, Gergely; Kun, Adám; Scheuring, István; Dieckmann, Ulf

    2012-01-01

    There is continuing interest in understanding factors that facilitate the evolution and stability of cooperation within and between species. Such interactions will often involve plasticity in investment behavior, in response to the interacting partner's investments. Our aim here is to investigate the evolution and stability of reciprocal investment behavior in interspecific interactions, a key phenomenon strongly supported by experimental observations. In particular, we present a comprehensive analysis of a continuous reciprocal investment game between mutualists, both in well-mixed and spatially structured populations, and we demonstrate a series of novel mechanisms for maintaining interspecific mutualism. We demonstrate that mutualistic partners invariably follow investment cycles, during which mutualism first increases, before both partners eventually reduce their investments to zero, so that these cycles always conclude with full defection. We show that the key mechanism for stabilizing mutualism is phase polymorphism along the investment cycle. Although mutualistic partners perpetually change their strategies, the community-level distribution of investment levels becomes stationary. In spatially structured populations, the maintenance of polymorphism is further facilitated by dynamic mosaic structures, in which mutualistic partners form expanding and collapsing spatial bubbles or clusters. Additionally, we reveal strategy-diversity thresholds, both for well-mixed and spatially structured mutualistic communities, and discuss factors for meeting these thresholds, and thus maintaining mutualism. Our results demonstrate that interspecific mutualism, when considered as plastic investment behavior, can be unstable, and, in agreement with empirical observations, may involve a polymorphism of investment levels, varying both in space and in time. Identifying the mechanisms maintaining such polymorphism, and hence mutualism in natural communities, provides a significant

  4. Strategy Diversity Stabilizes Mutualism through Investment Cycles, Phase Polymorphism, and Spatial Bubbles

    PubMed Central

    Boza, Gergely; Kun, Ádám; Scheuring, István; Dieckmann, Ulf

    2012-01-01

    There is continuing interest in understanding factors that facilitate the evolution and stability of cooperation within and between species. Such interactions will often involve plasticity in investment behavior, in response to the interacting partner's investments. Our aim here is to investigate the evolution and stability of reciprocal investment behavior in interspecific interactions, a key phenomenon strongly supported by experimental observations. In particular, we present a comprehensive analysis of a continuous reciprocal investment game between mutualists, both in well-mixed and spatially structured populations, and we demonstrate a series of novel mechanisms for maintaining interspecific mutualism. We demonstrate that mutualistic partners invariably follow investment cycles, during which mutualism first increases, before both partners eventually reduce their investments to zero, so that these cycles always conclude with full defection. We show that the key mechanism for stabilizing mutualism is phase polymorphism along the investment cycle. Although mutualistic partners perpetually change their strategies, the community-level distribution of investment levels becomes stationary. In spatially structured populations, the maintenance of polymorphism is further facilitated by dynamic mosaic structures, in which mutualistic partners form expanding and collapsing spatial bubbles or clusters. Additionally, we reveal strategy-diversity thresholds, both for well-mixed and spatially structured mutualistic communities, and discuss factors for meeting these thresholds, and thus maintaining mutualism. Our results demonstrate that interspecific mutualism, when considered as plastic investment behavior, can be unstable, and, in agreement with empirical observations, may involve a polymorphism of investment levels, varying both in space and in time. Identifying the mechanisms maintaining such polymorphism, and hence mutualism in natural communities, provides a significant

  5. The Central Symbiosis of Molecular Biology: Molecules in Mutualism.

    PubMed

    Lanier, Kathryn A; Petrov, Anton S; Williams, Loren Dean

    2017-08-07

    As illustrated by the mitochondrion and the eukaryotic cell, little in biology makes sense except in light of mutualism. Mutualisms are persistent, intimate, and reciprocal exchanges; an organism proficient in obtaining certain benefits confers those on a partner, which reciprocates by conferring different benefits. Mutualisms (i) increase fitness, (ii) inspire robustness, (iii) are resilient and resistant to change, (iv) sponsor co-evolution, (v) foster innovation, and (vi) involve partners that are distantly related with contrasting yet complementary proficiencies. Previous to this work, mutualisms were understood to operate on levels of cells, organisms, ecosystems, and even societies and economies. Here, the concepts of mutualism are extended to molecules and are seen to apply to the relationship between RNA and protein. Polynucleotide and polypeptide are Molecules in Mutualism. RNA synthesizes protein in the ribosome and protein synthesizes RNA in polymerases. RNA and protein are codependent, and trade proficiencies. Protein has proficiency in folding into complex three-dimensional states, contributing enzymes, fibers, adhesives, pumps, pores, switches, and receptors. RNA has proficiency in direct molecular recognition, achieved by complementary base pairing interactions, which allow it to maintain, record, and transduce information. The large phylogenetic distance that characterizes partnerships in organismal mutualism has close analogy with large distance in chemical space between RNA and protein. The RNA backbone is anionic and self-repulsive and cannot form hydrophobic structural cores. The protein backbone is neutral and cohesive and commonly forms hydrophobic cores. Molecules in Mutualism extends beyond RNA and protein. A cell is a consortium of molecules in which nucleic acids, proteins, polysaccharides, phospholipids, and other molecules form a mutualism consortium that drives metabolism and replication. Analogies are found in systems such as

  6. Role of MicroRNA in Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-07-01

    AD_________________ Award Number: W81XWH-11-1-0491 TITLE: Role of MicroRNA in Aggressive Prostate... MicroRNA in Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0491 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jer...action is not fully characterized. Using microRNA microarray screening, we found microRNA -363 (miR363) is significantly down regulated in several

  7. Trade-offs in an ant-plant-fungus mutualism.

    PubMed

    Orivel, Jérôme; Malé, Pierre-Jean; Lauth, Jérémie; Roux, Olivier; Petitclerc, Frédéric; Dejean, Alain; Leroy, Céline

    2017-03-15

    Species engaged in multiple, simultaneous mutualisms are subject to trade-offs in their mutualistic investment if the traits involved in each interaction are overlapping, which can lead to conflicts and affect the longevity of these associations. We investigate this issue via a tripartite mutualism involving an ant plant, two competing ant species and a fungus the ants cultivate to build galleries under the stems of their host plant to capture insect prey. The use of the galleries represents an innovative prey capture strategy compared with the more typical strategy of foraging on leaves. However, because of a limited worker force in their colonies, the prey capture behaviour of the ants results in a trade-off between plant protection (i.e. the ants patrol the foliage and attack intruders including herbivores) and ambushing prey in the galleries, which has a cascading effect on the fitness of all of the partners. The quantification of partners' traits and effects showed that the two ant species differed in their mutualistic investment. Less investment in the galleries (i.e. in fungal cultivation) translated into more benefits for the plant in terms of less herbivory and higher growth rates and vice versa. However, the greater vegetative growth of the plants did not produce a positive fitness effect for the better mutualistic ant species in terms of colony size and production of sexuals nor was the mutualist compensated by the wider dispersal of its queens. As a consequence, although the better ant mutualist is the one that provides more benefits to its host plant, its lower host-plant exploitation does not give this ant species a competitive advantage. The local coexistence of the ant species is thus fleeting and should eventually lead to the exclusion of the less competitive species.

  8. [Mutual Help Groups: diabetes and hypertension control strategy].

    PubMed

    Esqueda, Agustín Lara; Calderón, Arturo Aroch; Jiménez, Rosa Aurora; Guzmán, Mario Arceo; Monroy, Oscar Velázquez

    2004-01-01

    To evaluate the accomplishment of the treatment basic goals of every person with diabetes type 2 that attend the Mutual Help Groups (GAM) of the Mexican Ministry of Health (SS). This transversal comparative study was carried out in 15 Mexican states, through the accomplishment reports of the treatment basic goals of the GAM integrants by June of 2001, compared to the reported figures by the Health Information System for Open Population (SISPA), Ministry of Health on the same date. The studied variables are: age, sex, blood glucose, blood pressure, body mass index, physical activity and pharmacological treatment. The treatment basic goals accomplishment for 6, 958 people with diabetes was evaluated, all of them attended the Ministry of Health GAMs, in 15 of the 32 Mexican states including the Federal District. When comparing frequencies of patients with diabetes controlled by the GAM and the SISPA, a differential was appreciated, being observed a tendency that showed that people in the GAM were much more controlled; when analyzing with the test Student "t" the differences were even more significant (p < 0.005). The obese diabetics group had a higher risk of being uncontrolled, in relation to the group of non-obese diabetics (OR 1.8, CI: 1.06,1.32; p < 0.002). When comparing the sedentary to the non-sedentary group it was found that the sedentary diabetics presented 1.56 times higher risk of being uncontrolled, that those in the diabetes group that carried out physical activity (CI: 1.37,1.78; p < 0.001). The Mutual Help Groups are a fundamental strategy in the educational line for improving the disease control, since people with diabetes or hypertension and their relatives play an active role in treatment development accomplishment, as well as in the disease prevention and control. Unlike to that reported in the SISPA, the highest benefits of control, are achieved in people with diabetes or hypertension who attend the GAM.

  9. Mutualism fails when climate response differs between interacting species.

    PubMed

    Warren, Robert J; Bradford, Mark A

    2014-02-01

    Successful species interactions require that both partners share a similar cue. For many species, spring warming acts as a shared signal to synchronize mutualist behaviors. Spring flowering plants and the ants that disperse their seeds respond to warming temperatures so that ants forage when plants drop seeds. However, where warm-adapted ants replace cold-adapted ants, changes in this timing might leave early seeds stranded without a disperser. We investigate plant seed dispersal south and north of a distinct boundary between warm- and cold-adapted ants to determine if changes in the ant species influence local plant dispersal. The warm-adapted ants forage much later than the cold-adapted ants, and so we first assess natural populations of early and late blooming plants. We then transplant these plants south and north of the ant boundary to test whether distinct ant climate requirements disrupt the ant-plant mutualism. Whereas the early blooming plant's inability to synchronize with the warm-adapted ant leaves its populations clumped and patchy and its seedlings clustered around the parents in natural populations, when transplanted into the range of the cold-adapted ant, effective seed dispersal recovers. In contrast, the mutualism persists for the later blooming plant regardless of location because it sets seed later in spring when both warm- and cold-adapted ant species forage, resulting in effective seed dispersal. These results indicate that the climate response of species interactions, not just the species themselves, is integral in understanding ecological responses to a changing climate. Data linking phenological synchrony and dispersal are rare, and these results suggest a viable mechanism by which a species' range is limited more by biotic than abiotic interactions - despite the general assumption that biotic influences are buried within larger climate drivers. These results show that biotic partner can be as fundamental a niche requirement as abiotic

  10. Manipulating MicroRNAs in Murine Models: Targeting the Multi-Targeting in Epilepsy

    PubMed Central

    2017-01-01

    MicroRNAs are small noncoding RNAs that work posttranscriptionally to negatively regulate protein levels. They influence neuronal and glial structure and function, neuroinflammatory signaling, cell death, neurogenesis, and other processes relevant to epileptogenesis. Functional studies using oligonucleotide inhibitors (antagomirs) and mimics (agomirs) to modulate microRNAs in rat and mouse models of epilepsy show effects on evoked and spontaneous seizures and attendant neuropathology. The present review summarizes recent findings and points to gaps in our knowledge of the underlying mechanisms and directions for the future. PMID:28331471

  11. No Evidence of Emotional Dysregulation or Aversion to Mutual Gaze in Preschoolers with Autism Spectrum Disorder: An Eye-Tracking Pupillometry Study

    ERIC Educational Resources Information Center

    Nuske, Heather J.; Vivanti, Giacomo; Dissanayake, Cheryl

    2015-01-01

    The "gaze aversion hypothesis", suggests that people with Autism Spectrum Disorder (ASD) avoid mutual gaze because they experience it as hyper-arousing. To test this hypothesis we showed mutual and averted gaze stimuli to 23 mixed-ability preschoolers with ASD ("M" Mullen DQ = 68) and 21 typically-developing preschoolers, aged…

  12. No Evidence of Emotional Dysregulation or Aversion to Mutual Gaze in Preschoolers with Autism Spectrum Disorder: An Eye-Tracking Pupillometry Study

    ERIC Educational Resources Information Center

    Nuske, Heather J.; Vivanti, Giacomo; Dissanayake, Cheryl

    2015-01-01

    The "gaze aversion hypothesis", suggests that people with Autism Spectrum Disorder (ASD) avoid mutual gaze because they experience it as hyper-arousing. To test this hypothesis we showed mutual and averted gaze stimuli to 23 mixed-ability preschoolers with ASD ("M" Mullen DQ = 68) and 21 typically-developing preschoolers, aged…

  13. Analysis of gene expression EGFR and KRAS, microRNA-21 and microRNA-203 in patients with colon and rectal cancer and correlation with clinical outcome and prognostic factors.

    PubMed

    Carvalho, Thais Inácio de; Novais, Paulo Cezar; Lizarte, Fermino Sanches; Sicchieri, Renata Danielle; Rosa, Marcella Suelma Torrecillas; Carvalho, Camila Albuquerque Mello de; Tirapelli, Daniela Pretti da Cunha; Peria, Fernanda Maris; Rocha, José Joaquim Ribeiro da; Féres, Omar

    2017-03-01

    To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in colon and rectal cancer samples, correlated with their age at diagnosis, histological subtype, value of pretreatment CEA, TNM staging and clinical outcome. Expression of genes and microRNAs by real time PCR in tumor and non-tumor samples obtained from surgical treatment of 50 patients. An increased expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor samples was found. There was no statistically significant difference between the expression of these genes and microRNAs when compared to age at diagnosis and histological subtype. The EGFR gene showed higher expression in relation to the value of CEA diagnosis. The expression of microRNA-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission. The therapy of colon and rectum tumors based on microRNAs remains under investigation reserving huge potential for future applications and clinical interventions in conjunction with existing therapies. We expect, based on the exposed data, to stimulate the development of new therapeutic possibilities, making the treatment of these tumors more effective.

  14. Chemoprevention of Cigarette Smoke–Induced Alterations of MicroRNA Expression in Rat Lungs

    PubMed Central

    Izzotti, Alberto; Calin, George A.; Steele, Vernon E.; Cartiglia, Cristina; Longobardi, Mariagrazia; Croce, Carlo M.; De Flora, Silvio

    2015-01-01

    We previously showed that exposure to environmental cigarette smoke (ECS) for 28 days causes extensive downregulation of microRNA expression in the lungs of rats, resulting in the overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lungs of either ECS-free or ECS-exposed rats treated with the orally administered chemopreventive agents N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone, and phenethyl isothiocyanate (as single agents or in combinations). This is the first study of microRNA modulation by chemopreventive agents in nonmalignant tissues. Scatterplot, hierarchical cluster, and principal component analyses of microarray and quantitative PCR data showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, indicating potential safety. On the other hand, all of them attenuated ECS-induced alterations but to a variable extent and with different patterns, indicating potential preventive efficacy. The main ECS-altered functions that were modulated by chemopreventive agents included cell proliferation, apoptosis, differentiation, Ras activation, P53 functions, NF-κB pathway, transforming growth factor–related stress response, and angiogenesis. Some micro-RNAs known to be polymorphic in humans were downregulated by ECS and were protected by chemopreventive agents. This study provides proof-of-concept and validation of technology that we are further refining to screen and prioritize potential agents for continued development and to help elucidate their biological effects and mechanisms. Therefore, microRNA analysis may provide a new tool for predicting at early carcinogenesis stages both the potential safety and efficacy of cancer chemopreventive agents. PMID:20051373

  15. Alteration of microRNA expression in cerebrospinal fluid of unconscious patients after traumatic brain injury and a bioinformatic analysis of related single nucleotide polymorphisms.

    PubMed

    You, Wen-Dong; Tang, Qi-Lin; Wang, Lei; Lei, Jin; Feng, Jun-Feng; Mao, Qing; Gao, Guo-Yi; Jiang, Ji-Yao

    2016-01-01

    It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs). We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs. Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region. The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.

  16. Reduced expression of microRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11

    PubMed Central

    Drayton, Ross M; Dudziec, Ewa; Peter, Stefan; Bertz, Simone; Hartmann, Arndt; Bryant, Helen E; Catto, James WF

    2014-01-01

    Purpose Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug resistant phenotype and how this resistance might be overcome. Experimental Design MicroRNA expression in paired cisplatin resistant and sensitive cell lines was measured. Dysregulated microRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione. Candidate microRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and microRNA-27a were quantified in patient tumour material. Results A panel of microRNAs were found to be dysregulated in cisplatin resistant cells. MicroRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of glutathione biosynthesis. In patients, SLC7A11 expression was inversely related to microRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring microRNA-27a expression, or reducing SLC7A11 activity with an siRNA or with sulfasalazine. Conclusion Our findings indicate that microRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease. PMID:24516043

  17. Mutual Information Between GPS Measurements and Earthquakes

    NASA Astrophysics Data System (ADS)

    Wang, T.; Bebbington, M. S.

    2009-12-01

    Prior to the wide deployment of Continuous GPS stations in the early 1990s, there were a number of well-documented deformation rate changes observed before large earthquakes. GPS measurements provide the opportunity for systematic investigation of pre-, co- and post-seismic deformation anomalies, but contain much noise that needs to be filtered out of the observations. Assuming the existence of an earthquake cycle (for example, mainshock--aftershock--quiescence--precursory seismicity), a hidden Markov model (HMM) provides a natural framework for analyzing the observed GPS data. For two case studies of a) deep earthquakes in the central North Island, New Zealand, and b) shallow earthquakes in Southern California, an HMM fitted to the trend ranges of the GPS measurements can classify the deformation data into different patterns which form proxies for states of the earthquake cycle. Mutual information can be used to examine whether there is any relation between these patterns, in particular the Viterbi path, and subsequent (or previous) earthquakes. One class of GPS movements (identified by the HMM as having the largest range of deformation rate changes) appears to have some precursory character for earthquakes with minimum magnitude 5.1 (central North Island, New Zealand, 26 earthquakes in 1747 days) and 4.5 (Southern California, 50 earthquakes in 3815 days). We define a ``Time of Increased Probability'' (TIP) as being a 10-day interval (central North Island, New Zealand) or a 20-day interval (Southern California) following entry (as identified by the Viterbi algorithm) to the `precursory' hidden state, and examine the performance of this in probabilistically forecasting subsequent earthquakes.

  18. Novel Fabrication of MicroRNA Nanoparticle-Coated Coronary Stent for Prevention of Post-Angioplasty Restenosis

    PubMed Central

    Che, Hui-Lian; Bae, In-Ho; Lim, Kyung Seob; Uthaman, Saji; Song, In Taek; Lee, Haeshin; Lee, Duhwan; Kim, Won Jong; Ahn, Youngkeun; Jeong, Myung-Ho

    2016-01-01

    Background and Objectives MicroRNA 145 is known to be responsible for cellular proliferation, and its enhanced expression reportedly inhibits the retardation of vascular smooth muscle cell growth specifically. In this study, we developed a microRNA 145 nanoparticle immobilized, hyaluronic acid (HA)-coated stent. Materials and Methods For the gene therapy, we used disulfide cross-linked low molecular polyethylenimine as the carrier. The microRNA 145 was labeled with YOYO-1 and the fluorescent microscopy images were obtained. The release of microRNA 145 from the stent was measured with an ultra violet spectrophotometer. The downstream targeting of the c-Myc protein and green fluorescent protein was determined by Western blotting. Finally, we deployed microRNA 145/ssPEI nanoparticles immobilized on HA-coated stents in the balloon-injured external iliac artery in a rabbit restenosis model. Results Cellular viability of the nanoparticle-immobilized surface tested using A10 vascular smooth muscle cells showed that MSN exhibited negligible cytotoxicity. In addition, microRNA 145 and downstream signaling proteins were identified by western blots with smooth muscle cell (SMC) lysates from the transfected A10 cell, as the molecular mechanism for decreased SMC proliferation that results in the inhibition of in-stent restenosis. MicroRNA 145 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis at the post-implantation. We investigated the qualitative analyses of in-stent restenosis in the rabbit model using micro-computed tomography imaging and histological staining. Conclusion MicroRNA 145-eluting stent mitigated in-stent restenosis efficiently with no side effects and can be considered a successful substitute to the current drug-eluting stent. PMID:26798382

  19. Transcriptome-wide analysis of compression-induced microRNA expression alteration in breast cancer for mining therapeutic targets.

    PubMed

    Kim, Baek Gil; Kang, Suki; Han, Hyun Ho; Lee, Joo Hyun; Kim, Ji Eun; Lee, Sung Hwan; Cho, Nam Hoon

    2016-05-10

    Tumor growth-generated mechanical compression may increase or decrease expression of microRNAs, leading to tumor progression. However, little is known about whether mechanical compression induces aberrant expression of microRNAs in cancer and stromal cells. To investigate the relationship between compression and microRNA expression, microRNA array analysis was performed with breast cancer cell lines and cancer-associated fibroblasts (CAFs) exposed to different compressive conditions. In our study, mechanical compression induced alteration of microRNA expression level in breast cancer cells and CAFs. The alteration was greater in the breast cancer cells than CAFs. Mechanical compression mainly induced upregulation of microRNAs rather than downregulation. In a parallel mRNA array analysis, more than 25% of downregulated target genes were functionally involved in tumor suppression (apoptosis, cell adhesion, and cell cycle arrest), whereas generally less than 15% were associated with tumor progression (epithelial-mesenchymal transition, migration, invasion, and angiogenesis). Of all cells examined, MDA-MB-231 cells showed the largest number of compression-upregulated microRNAs. miR-4769-5p and miR-4446-3p were upregulated by compression in both MDA-MB-231 cells and CAFs. Our results suggest that mechanical compression induces changes in microRNA expression level, which contribute to tumor progression. In addition, miR-4769-5p and miR-4446-3p may be potential therapeutic targets for incurable cancers, such as triple negative breast cancer, in that this would reduce or prevent downregulation of tumor-suppressing genes in both the tumor and its microenvironment simultaneously.

  20. Transcriptome-wide analysis of compression-induced microRNA expression alteration in breast cancer for mining therapeutic targets

    PubMed Central

    Kim, Baek Gil; Kang, Suki; Han, Hyun Ho; Lee, Joo Hyun; Kim, Ji Eun; Lee, Sung Hwan; Cho, Nam Hoon

    2016-01-01

    Tumor growth–generated mechanical compression may increase or decrease expression of microRNAs, leading to tumor progression. However, little is known about whether mechanical compression induces aberrant expression of microRNAs in cancer and stromal cells. To investigate the relationship between compression and microRNA expression, microRNA array analysis was performed with breast cancer cell lines and cancer-associated fibroblasts (CAFs) exposed to different compressive conditions. In our study, mechanical compression induced alteration of microRNA expression level in breast cancer cells and CAFs. The alteration was greater in the breast cancer cells than CAFs. Mechanical compression mainly induced upregulation of microRNAs rather than downregulation. In a parallel mRNA array analysis, more than 25% of downregulated target genes were functionally involved in tumor suppression (apoptosis, cell adhesion, and cell cycle arrest), whereas generally less than 15% were associated with tumor progression (epithelial-mesenchymal transition, migration, invasion, and angiogenesis). Of all cells examined, MDA-MB-231 cells showed the largest number of compression-upregulated microRNAs. miR-4769-5p and miR-4446-3p were upregulated by compression in both MDA-MB-231 cells and CAFs. Our results suggest that mechanical compression induces changes in microRNA expression level, which contribute to tumor progression. In addition, miR-4769-5p and miR-4446-3p may be potential therapeutic targets for incurable cancers, such as triple negative breast cancer, in that this would reduce or prevent downregulation of tumor-suppressing genes in both the tumor and its microenvironment simultaneously. PMID:27027350

  1. The microRNA toolkit of insects

    PubMed Central

    Ylla, Guillem; Fromm, Bastian; Piulachs, Maria-Dolors; Belles, Xavier

    2016-01-01

    Is there a correlation between miRNA diversity and levels of organismic complexity? Exhibiting extraordinary levels of morphological and developmental complexity, insects are the most diverse animal class on earth. Their evolutionary success was in particular shaped by the innovation of holometabolan metamorphosis in endopterygotes. Previously, miRNA evolution had been linked to morphological complexity, but astonishing variation in the currently available miRNA complements of insects made this link unclear. To address this issue, we sequenced the miRNA complement of the hemimetabolan Blattella germanica and reannotated that of two other hemimetabolan species, Locusta migratoria and Acyrthosiphon pisum, and of four holometabolan species, Apis mellifera, Tribolium castaneum, Bombyx mori and Drosophila melanogaster. Our analyses show that the variation of insect miRNAs is an artefact mainly resulting from poor sampling and inaccurate miRNA annotation, and that insects share a conserved microRNA toolkit of 65 families exhibiting very low variation. For example, the evolutionary shift toward a complete metamorphosis was accompanied only by the acquisition of three and the loss of one miRNA families. PMID:27883064

  2. MicroRNA 33 Regulates Glucose Metabolism

    PubMed Central

    Ramírez, Cristina M.; Goedeke, Leigh; Rotllan, Noemi; Yoon, Je-Hyun; Cirera-Salinas, Daniel; Mattison, Julie A.; Suárez, Yajaira; de Cabo, Rafael; Gorospe, Myriam

    2013-01-01

    Metabolic diseases are characterized by the failure of regulatory genes or proteins to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators, recent discoveries have shown the remarkable role of small noncoding RNAs (microRNAs [miRNAs]) in the posttranscriptional regulation of gene expression. In this regard, we have recently demonstrated that miR-33a and miR33b, intronic miRNAs located within the sterol regulatory element-binding protein (SREBP) genes, regulate lipid metabolism in concert with their host genes. Here, we show that miR-33b also cooperates with SREBP1 in regulating glucose metabolism by targeting phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), key regulatory enzymes of hepatic gluconeogenesis. Overexpression of miR-33b in human hepatic cells inhibits PCK1 and G6PC expression, leading to a significant reduction of glucose production. Importantly, hepatic SREBP1c/miR-33b levels correlate inversely with the expression of PCK1 and G6PC upon glucose infusion in rhesus monkeys. Taken together, these results suggest that miR-33b works in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis, highlighting the clinical potential of miR-33a/b as novel therapeutic targets for a range of metabolic diseases. PMID:23716591

  3. MicroRNAs as Haematopoiesis Regulators

    PubMed Central

    Undi, Ram Babu; Kandi, Ravinder; Gutti, Ravi Kumar

    2013-01-01

    The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis. PMID:24454381

  4. MicroRNA in Teleost Fish

    PubMed Central

    Bizuayehu, Teshome Tilahun; Babiak, Igor

    2014-01-01

    MicroRNAs (miRNAs) are transcriptional and posttranscriptional regulators involved in nearly all known biological processes in distant eukaryotic clades. Their discovery and functional characterization have broadened our understanding of biological regulatory mechanisms in animals and plants. They show both evolutionary conserved and unique features across Metazoa. Here, we present the current status of the knowledge about the role of miRNA in development, growth, and physiology of teleost fishes, in comparison to other vertebrates. Infraclass Teleostei is the most abundant group among vertebrate lineage. Fish are an important component of aquatic ecosystems and human life, being the prolific source of animal proteins worldwide and a vertebrate model for biomedical research. We review miRNA biogenesis, regulation, modifications, and mechanisms of action. Specific sections are devoted to the role of miRNA in teleost development, organogenesis, tissue differentiation, growth, regeneration, reproduction, endocrine system, and responses to environmental stimuli. Each section discusses gaps in the current knowledge and pinpoints the future directions of research on miRNA in teleosts. PMID:25053657

  5. Dopamine Receptor D2 and Associated microRNAs Are Involved in Stress Susceptibility and Resistance to Escitalopram Treatment

    PubMed Central

    Zhang, Yi; Wang, Yuting; Wang, Lei; Bai, Mei; Zhang, Xiuwu

    2015-01-01

    Background: Early life stress has been demonstrated to increase the risk of developing depression in adulthood. However, the roles and associated molecular mechanisms of stresses in the onset and relapse of depression have yet to be fully elucidated. Methods: Depression-like behaviors were induced in rats by maternal deprivation and chronic unpredictable stress. Depression- and anxiety-like behaviors of rats, dopamine receptor D2 level, and microRNAs expression in rats’ brain tissues were measured. Results: Chronic unpredictable stress alone induced depression-like behaviors in rats, but maternal deprivation enhanced the effect of chronic unpredictable stress. Escitalopram significantly decreased depression-like behaviors in chronic unpredictable stress rats but was less effective in maternal deprivation with chronic unpredictable stress rats. Maternal deprivation increased dopamine receptor D2 messenger RNA expression and decreased microRNA-9 expression in the striatum. Chronic unpredictable stress increased dopamine receptor D2 mRNA and protein levels and decreased microRNA-9 expression in the nucleus accumbens. Furthermore, maternal deprivation enhanced the effect of chronic unpredictable stress on dopamine receptor D2 gene and microRNA-9 expression. Chronic unpredictable stress increased the expression of microRNA-326 in the nucleus accumbens but decreased it in the striatum, whereas maternal deprivation elevated microRNA-326 expression in the striatum. Escitalopram normalized microRNA-326 expression but had no effect on the expression of microRNA-9, dopamine receptor D2 mRNA, and dopamine receptor D2 protein in both the nucleus accumbens and striatum. The in vitro study showed that only microRNA-9 directly targeted the 3’ untranslated region of dopamine receptor D2 mRNA and inhibited dopamine receptor D2 protein expression. Conclusion: Early life stress enhanced the susceptibility to late life stress and resistance to escitalopram treatment through

  6. Butterfly effect and holographic mutual information under external field and spatial noncommutativity

    NASA Astrophysics Data System (ADS)

    Huang, Wung-Hong; Du, Yi-Hsien

    2017-02-01

    We apply the transformation of mixing azimuthal and internal coordinate or mixing time and internal coordinate to a stack of N black M-branes to find the Melvin spacetime of a stack of N black D-branes with magnetic or electric flux in string theory, after the Kaluza-Klein reduction. We slightly extend previous formulas to investigate the external magnetic and electric effects on the butterfly effect and holographic mutual information. It shows that the Melvin fields do not modify the scrambling time and will enhance the mutual information. In addition, we also T-dualize and twist a stack of N black D-branes to find a Melvin Universe supported by the flux of the NSNS b-field, which describes a non-comutative spacetime. It also shows that the spatial noncommutativity does not modify the scrambling time and will enhance the mutual information. We also study the corrected mutual information in the backreaction geometry due to the shock wave in our three model spacetimes.

  7. Lack of fidelity revealed in an insect-fungal mutualism after invasion.

    PubMed

    Wooding, Amy L; Wingfield, Michael J; Hurley, Brett P; Garnas, Jeffrey R; de Groot, Peter; Slippers, Bernard

    2013-08-23

    Symbiont fidelity is an important mechanism in the evolution and stability of mutualisms. Strict fidelity has been assumed for the obligate mutualism between Sirex woodwasps and their mutualistic Amylostereum fungi. This assumption has been challenged in North America where the European woodwasp, Sirex noctilio, and its fungal mutualist, Amylostereum areolatum, have recently been introduced. We investigate the specificity of the mutualism between Sirex and Amylostereum species in Canada, where S. noctilio co-infests Pinus with native Sirex nigricornis and its mutualist, Amylostereum chailletii. Using phylogenetic and culture methods, we show that extensive, reciprocal exchange of fungal species and strains is occurring, with 75.3 per cent of S. nigricornis carrying A. areolatum and 3.5 per cent of S. noctilio carrying A. chailletii. These findings show that the apparent specificity of the mutualism between Sirex spp. and their associated Amylostereum spp. is not the result of specific biological mechanisms that maintain symbiont fidelity. Rather, partner switching may be common when shifting geographical distributions driven by ecological or anthropogenic forces bring host and mutualist pairs into sympatry. Such novel associations have potentially profound consequences for fitness and virulence. Symbiont sharing, if it occurs commonly, may represent an important but overlooked mechanism of community change linked to biological invasions.

  8. Mutualism favours higher host specificity than does antagonism in plant–herbivore interaction

    PubMed Central

    Kawakita, Atsushi; Okamoto, Tomoko; Goto, Ryutaro; Kato, Makoto

    2010-01-01

    Coevolved mutualisms often exhibit high levels of partner specificity. Obligate pollination mutualisms, such as the fig–fig wasp and yucca–yucca moth systems, represent remarkable examples of such highly species-specific associations; however, the evolutionary processes underlying these patterns are poorly understood. The prevailing hypothesis suggests that the high degree of specificity in pollinating seed parasites is the fortuitous result of specialization in their ancestors because these insects are derived from endophytic herbivores that are themselves highly host-specific. Conversely, we show that in the Glochidion–Epicephala obligate pollination mutualism, pollinators are more host-specific than are closely related endophytic leaf-feeding taxa, which co-occur with Epicephala on the same Glochidion hosts. This difference is probably not because of shifts in larval diet (i.e. from leaf- to seed-feeding), because seed-eating lepidopterans other than Epicephala do not show the same degree of host specificity as Epicephala. Species of a tentative sister group of Epicephala each attack several distantly related plants, suggesting that the evolution of strict host specificity is tied to the evolution of pollinator habit. These results suggest that mutualists can attain higher host specificity than that of their parasitic ancestors and that coevolutionary selection can be a strong promoter of extreme reciprocal specialization in mutualisms. PMID:20427340

  9. Plant chemical defence: a partner control mechanism stabilising plant - seed-eating pollinator mutualisms

    PubMed Central

    Ibanez, Sébastien; Gallet, Christiane; Dommanget, Fanny; Després, Laurence

    2009-01-01

    Background Mutualisms are inherently conflictual as one partner always benefits from reducing the costs imposed by the other. Despite the widespread recognition that mutualisms are essentially reciprocal exploitation, there are few documented examples of traits that limit the costs of mutualism. In plant/seed-eating pollinator interactions the only mechanisms reported so far are those specific to one particular system, such as the selective abortion of over-exploited fruits. Results This study shows that plant chemical defence against developing larvae constitutes another partner sanction mechanism in nursery mutualisms. It documents the chemical defence used by globeflower Trollius europaeus L. (Ranunculaceae) against the seed-eating larvae of six pollinating species of the genus Chiastocheta Pokorny (Anthomyiidae). The correlative field study carried out shows that the severity of damage caused by Chiastocheta larvae to globeflower fruits is linked to the accumulation in the carpel walls of a C-glycosyl-flavone (adonivernith), which reduces the larval seed predation ability per damaged carpel. The different Chiastocheta species do not exploit the fruit in the same way and their interaction with the plant chemical defence is variable, both in terms of induction intensity and larval sensitivity to adonivernith. Conclusion Adonivernith accumulation and larval predation intensity appear to be both the reciprocal cause and effect. Adonivernith not only constitutes an effective chemical means of partner control, but may also play a key role in the sympatric diversification of the Chiastocheta genus. PMID:19887006

  10. The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells

    PubMed Central

    Gambardella, Gennaro; Carissimo, Annamaria; Chen, Amy; Cutillo, Luisa; Nowakowski, Tomasz J.; di Bernardo, Diego; Blelloch, Robert

    2017-01-01

    MicroRNAs act posttranscriptionally to suppress multiple target genes within a cell population. To what extent this multi-target suppression occurs in individual cells and how it impacts transcriptional heterogeneity and gene co-expression remains unknown. Here we used single-cell sequencing combined with introduction of individual microRNAs. miR-294 and let-7c were introduced into otherwise microRNA-deficient Dgcr8 knockout mouse embryonic stem cells. Both microRNAs induce suppression and correlated expression of their respective gene targets. The two microRNAs had opposing effects on transcriptional heterogeneity within the cell population, with let-7c increasing and miR-294 decreasing the heterogeneity between cells. Furthermore, let-7c promotes, whereas miR-294 suppresses, the phasing of cell cycle genes. These results show at the individual cell level how a microRNA simultaneously has impacts on its many targets and how that in turn can influence a population of cells. The findings have important implications in the understanding of how microRNAs influence the co-expression of genes and pathways, and thus ultimately cell fate. PMID:28102192

  11. SimiRa: A tool to identify coregulation between microRNAs and RNA-binding proteins

    PubMed Central

    Preusse, Martin; Marr, Carsten; Saunders, Sita; Maticzka, Daniel; Lickert, Heiko; Backofen, Rolf; Theis, Fabian

    2015-01-01

    microRNAs and microRNA-independent RNA-binding proteins are 2 classes of post-transcriptional regulators that have been shown to cooperate in gene-expression regulation. We compared the genome-wide target sets of microRNAs and RBPs identified by recent CLIP-Seq technologies, finding that RBPs have distinct target sets and favor gene interaction network hubs. To identify microRNAs and RBPs with a similar functional context, we developed simiRa, a tool that compares enriched functional categories such as pathways and GO terms. We applied simiRa to the known functional cooperation between Pumilio family proteins and miR-221/222 in the regulation of tumor supressor gene p27 and show that the cooperation is reflected by similar enriched categories but not by target genes. SimiRa also predicts possible cooperation of microRNAs and RBPs beyond direct interaction on the target mRNA for the nuclear RBP TAF15. To further facilitate research into cooperation of microRNAs and RBPs, we made simiRa available as a web tool that displays the functional neighborhood and similarity of microRNAs and RBPs: http://vsicb-simira.helmholtz-muenchen.de. PMID:26383775

  12. microRNAs and Prostate Cancer

    PubMed Central

    Josson, Sajni; Chung, Leland W. K.

    2016-01-01

    microRNAs are noncoding RNAs that are important for embryonic stem cell development and epithelial to mesenchymal transition (EMT). Tumor cells hijack EMT and stemness to grow and metastasize to distant organs including bone. In the tumor microenvironment, tumor cells interact with the stromal fibroblasts at the primary and metastatic sites and this interaction leads to tumor growth, EMT, and bone metastasis. Tumor-stromal interactions are a dynamic process that involves both cell–cell communications and extracellular vesicles and soluble factors. Growing body of evidence suggests that microRNAs are part of the payload that comprises the extracellular vesicles. microRNAs induce reactive stroma and thus convert normal stroma into tumor-associated stroma to promote aggressive tumorigenicity in vitro and in vivo. Landmark published studies demonstrate that expression of specific microRNAs of DLK1-DIO3 stem cell cluster correlates with patient survival in metastatic prostate cancer. Thus, microRNAs mediate tumor growth, EMT, and metastasis through cell intrinsic mechanisms and extracellular communications and could be novel biomarkers and therapeutic targets in bone metastatic prostate cancer. PMID:26658999

  13. microRNAs and Prostate Cancer.

    PubMed

    Josson, Sajni; Chung, Leland W K; Gururajan, Murali

    2015-01-01

    microRNAs are noncoding RNAs that are important for embryonic stem cell development and epithelial to mesenchymal transition (EMT). Tumor cells hijack EMT and stemness to grow and metastasize to distant organs including bone. In the tumor microenvironment, tumor cells interact with the stromal fibroblasts at the primary and metastatic sites and this interaction leads to tumor growth, EMT, and bone metastasis. Tumor-stromal interactions are a dynamic process that involves both cell-cell communications and extracellular vesicles and soluble factors. Growing body of evidence suggests that microRNAs are part of the payload that comprises the extracellular vesicles. microRNAs induce reactive stroma and thus convert normal stroma into tumor-associated stroma to promote aggressive tumorigenicity in vitro and in vivo. Landmark published studies demonstrate that expression of specific microRNAs of DLK1-DIO3 stem cell cluster correlates with patient survival in metastatic prostate cancer. Thus, microRNAs mediate tumor growth, EMT, and metastasis through cell intrinsic mechanisms and extracellular communications and could be novel biomarkers and therapeutic targets in bone metastatic prostate cancer.

  14. MicroRNAs in lung cancer

    PubMed Central

    Joshi, Pooja; Middleton, Justin; Jeon, Young-Jun; Garofalo, Michela

    2014-01-01

    MicroRNAs have become recognized as key players in the development of cancer. They are a family of small non-coding RNAs that can negatively regulate the expression of cancer-related genes by sequence-selective targeting of mRNAs, leading to either mRNA degradation or translational repression. Lung cancer is the leading cause of cancer-related death worldwide with a substantially low survival rate. MicroRNAs have been confirmed to play roles in lung cancer development, epithelial-mesenchymal transition and response to therapy. They are also being studied for their future use as diagnostic and prognostic biomarkers and as potential therapeutic targets. In this review we focus on the role of dysregulated microRNA expression in lung tumorigenesis. We also discuss the role of microRNAs in therapeutic resistance and as biomarkers. We further look into the progress made and challenges remaining in using microRNAs for therapy in lung cancer. PMID:25332906

  15. microRNAs in Diabetic Kidney Disease.

    PubMed

    Chung, Arthur C K

    2015-01-01

    Diabetes and diabetic kidney diseases have continually exerted a great burden on our society. Although the recent advances in medical research have led to a much better understanding of diabetic kidney diseases, there is still no successful strategy for effective treatments for diabetic kidney diseases. Recently, treatment of diabetic kidney diseases relies either on drugs that reduce the progression of renal injury or on renal replacement therapies, such as dialysis and kidney transplantation. On the other hand, searching for biomarkers for early diagnosis and effective therapy is also urgent. Discovery of microRNAs has opened to a novel field for posttranscriptional regulation of gene expression. Results from cell culture experiments, experimental animal models, and patients under diabetic conditions reveal the critical role of microRNAs during the progression of diabetic kidney diseases. Functional studies demonstrate not only the capability of microRNAs to regulate expression of target genes, but also their therapeutic potential to diabetic kidney diseases. The existence of microRNAs in plasma, serum, and urine suggests their possibility to be biomarkers in diabetic kidney diseases. Thus, identification of the functional role of microRNAs provides an essentially clinical impact in terms of prevention and treatment of progression in diabetic kidney diseases as it enables us to develop novel, specific therapies and diagnostic tools for diabetic kidney diseases.

  16. microRNAs: key triggers of neuronal cell fate.

    PubMed

    Meza-Sosa, Karla F; Pedraza-Alva, Gustavo; Pérez-Martínez, Leonor

    2014-01-01

    Development of the central nervous system (CNS) requires a precisely coordinated series of events. During embryonic development, different intra- and extracellular signals stimulate neural stem cells to become neural progenitors, which eventually irreversibly exit from the cell cycle to begin the first stage of neurogenesis. However, before this event occurs, the self-renewal and proliferative capacities of neural stem cells and neural progenitors must be tightly regulated. Accordingly, the participation of various evolutionary conserved microRNAs is key in distinct central nervous system (CNS) developmental processes of many organisms including human, mouse, chicken, frog, and zebrafish. microRNAs specifically recognize and regulate the expression of target mRNAs by sequence complementarity within the mRNAs 3' untranslated region and importantly, a single microRNA can have several target mRNAs to regulate a process; likewise, a unique mRNA can be targeted by more than one microRNA. Thus, by regulating different target genes, microRNAs let-7, microRNA-124, and microRNA-9 have been shown to promote the differentiation of neural stem cells and neural progenitors into specific neural cell types while microRNA-134, microRNA-25 and microRNA-137 have been characterized as microRNAs that induce the proliferation of neural stem cells and neural progenitors. Here we review the mechanisms of action of these two sets of microRNAs and their functional implications during the transition from neural stem cells and neural progenitors to fully differentiated neurons. The genetic and epigenetic mechanisms that regulate the expression of these microRNAs as well as the role of the recently described natural RNA circles which act as natural microRNA sponges regulating post-transcriptional microRNA expression and function during the early stages of neurogenesis is also discussed.

  17. microRNAs: key triggers of neuronal cell fate

    PubMed Central

    Meza-Sosa, Karla F.; Pedraza-Alva, Gustavo; Pérez-Martínez, Leonor

    2014-01-01

    Development of the central nervous system (CNS) requires a precisely coordinated series of events. During embryonic development, different intra- and extracellular signals stimulate neural stem cells to become neural progenitors, which eventually irreversibly exit from the cell cycle to begin the first stage of neurogenesis. However, before this event occurs, the self-renewal and proliferative capacities of neural stem cells and neural progenitors must be tightly regulated. Accordingly, the participation of various evolutionary conserved microRNAs is key in distinct central nervous system (CNS) developmental processes of many organisms including human, mouse, chicken, frog, and zebrafish. microRNAs specifically recognize and regulate the expression of target mRNAs by sequence complementarity within the mRNAs 3′ untranslated region and importantly, a single microRNA can have several target mRNAs to regulate a process; likewise, a unique mRNA can be targeted by more than one microRNA. Thus, by regulating different target genes, microRNAs let-7, microRNA-124, and microRNA-9 have been shown to promote the differentiation of neural stem cells and neural progenitors into specific neural cell types while microRNA-134, microRNA-25 and microRNA-137 have been characterized as microRNAs that induce the proliferation of neural stem cells and neural progenitors. Here we review the mechanisms of action of these two sets of microRNAs and their functional implications during the transition from neural stem cells and neural progenitors to fully differentiated neurons. The genetic and epigenetic mechanisms that regulate the expression of these microRNAs as well as the role of the recently described natural RNA circles which act as natural microRNA sponges regulating post-transcriptional microRNA expression and function during the early stages of neurogenesis is also discussed. PMID:25009466

  18. MicroRNA in cell differentiation and development.

    PubMed

    Shi, Yi; Jin, YouXin

    2009-03-01

    The regulation of gene expression by microRNAs (miRNAs) is a recently discovered pattern of gene regulation in animals and plants. MiRNAs have been implicated in various aspects of animal development and cell differentiation, such as early embryonic development, neuronal development, muscle development, and lymphocyte development, by the analysis of genetic deletions of individual miRNAs in mammals. These studies show that miRNAs are key regulators in animal development and are potential causes of human diseases. Here we review some recent discoveries about the functions of miRNAs in cell differentiation and development.

  19. Thinking about RNA? MicroRNAs in the brain.

    PubMed

    Barbato, Christian; Giorgi, Corinna; Catalanotto, Caterina; Cogoni, Carlo

    2008-08-01

    MicroRNAs (miRNAs) are a recently discovered class of small RNA molecules implicated in a wide range of diverse gene regulatory mechanisms. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system. This suggests that gene regulation networks based on miRNA activities may be particularly relevant in neurons. Recent studies show the involvement of RNA-mediated gene silencing in neurogenesis, neural differentiation, synaptic plasticity, and neurologic and psychiatric diseases. This review focuses on the roles of miRNAs in the gene regulation of the nervous system.

  20. Identification of microRNAs expressed in the midgut of Aedes albopictus during dengue infection.

    PubMed

    Su, Jianxin; Li, Chunxiao; Zhang, Yingmei; Yan, Ting; Zhu, Xiaojuan; Zhao, Minghui; Xing, Dan; Dong, Yande; Guo, Xiaoxia; Zhao, Tongyan

    2017-02-03

    The midgut is the first barrier to dengue virus (DENV) infections of mosquitoes and therefore is a major bottleneck for the subsequent development of vector competence. However, the molecular mechanisms responsible for this barrier are unknown. We constructed three small RNA libraries from the midguts of adult Aedes albopictus females that had been fed on either sugar solution, an uninfected blood meal, or a blood meal infected with DENV-2, and112 conserved microRNAs represented by 173 miRNA sequences were identified, with 34 novel microRNAs predicted by Mireap, RNAfold and Sfold software. In addition, the expression of aal-miR-1174, aal-miR-2951 and aal-miR-956 was confirmed via stem-loop quantitative real-time PCR (qRT-PCR). Compared with microRNA expression profiles of mosquitoes that had ingested a regular blood meal, 43 microRNAs were upregulated and 4were downregulated in mosquitoes that had ingested a DENV-2-infected blood meal. Among the differentially expressed microRNAs, miR-1767, miR-276-3p, miR-4448 and miR-4728-5p were verified via stem-loop qRT-PCR. Analyses indicated that the changing patterns in miRNA expression during DENV-2 infection were significant and varied at different time points post infection. Most miRNA were upregulated at 24 h but were downregulated at 48 h post DENV-2 intake. The aal-miR-4728-5p was chosen for an in vitro transient transfection assay, and the results show that this miRNA enhances DENV replication in C6/36 cells. This study provides the first information on microRNAs expressed in the midgut of Ae. albopictus and describes species-specific changes in their expression levels following infection by DENV-2.

  1. [Effect of xenobiotics on microRNA expression in rat liver].

    PubMed

    Gulyaeva, L F; Chanyshev, M D; Kolmykov, S K; Ushakov, D S; Nechkin, S S

    2016-01-01

    Using bioinformatics analysis we selected microRNAs which could bind 3'-UTR-region of cytochrome P450 (CYP) genes. Three microRNA miR-21, -221, -222, their potential targets might be mRNA for CYP1A1, and two microRNA miR-143, miR-152 for CYP2B1 accordingly were selected for experimental verification. Expression level of these microRNAs in rat liver upon benzo(a)pyrene (BP), phenobarbital (PB), and DDT induction was determined using RT-qPCR method. In rats treated by both BP, and DDT the hepatic content of miR-21, -221, -222 significantly demonstrated a 2-3-fold decrease. The decrease in miR expression was accompanied by a considerable (5.5-8.7-fold) increase in the CYP1A1-mediated EROD activity. The expression of miR-143 remained unchanged after the PB treatment, while the expression of miR-152 increased by 2 times, however, the (10.5-fold) increase in PROD activity of CYP2B was much higher. In the DDT-treated liver PROD activity increased by 20 times, the expression of miR-152 didn't change, and the expression of miR-143 increased by 2 times. The bioinformatics analysis of interactions between microRNAs and targets showed that the studied miRs can potentially bind 3'-end of AhR, ESR1, GR, CCND1, PTEN mRNA. Thus, the expression profile of miR-21, -221, -222, -143, -152 might change under the xenobiotics exposure. In silico analysis confirmed, that microRNAs target not only cytochrome P450 mRNA but also other genes, including those involved in hormonal carcinogenesis, they also can be regulated with studied miRs.

  2. MicroRNAs in Honey Bee Caste Determination

    PubMed Central

    Ashby, Regan; Forêt, Sylvain; Searle, Iain; Maleszka, Ryszard

    2016-01-01

    The cellular mechanisms employed by some organisms to produce contrasting morphological and reproductive phenotypes from the same genome remains one of the key unresolved issues in biology. Honeybees (Apis mellifera) use differential feeding and a haplodiploid sex determination system to generate three distinct organismal outcomes from the same genome. Here we investigate the honeybee female and male caste-specific microRNA and transcriptomic molecular signatures during a critical time of larval development. Both previously undetected and novel miRNAs have been discovered, expanding the inventory of these genomic regulators in invertebrates. We show significant differences in the microRNA and transcriptional profiles of diploid females relative to haploid drone males as well as between reproductively distinct females (queens and workers). Queens and drones show gene enrichment in physio-metabolic pathways, whereas workers show enrichment in processes associated with neuronal development, cell signalling and caste biased structural differences. Interestingly, predicted miRNA targets are primarily associated with non-physio-metabolic genes, especially neuronal targets, suggesting a mechanistic disjunction from DNA methylation that regulates physio-metabolic processes. Accordingly, miRNA targets are under-represented in methylated genes. Our data show how a common set of genetic elements are differentially harnessed by an organism, which may provide the remarkable level of developmental flexibility required. PMID:26739502

  3. MicroRNAs in Honey Bee Caste Determination.

    PubMed

    Ashby, Regan; Forêt, Sylvain; Searle, Iain; Maleszka, Ryszard

    2016-01-07

    The cellular mechanisms employed by some organisms to produce contrasting morphological and reproductive phenotypes from the same genome remains one of the key unresolved issues in biology. Honeybees (Apis mellifera) use differential feeding and a haplodiploid sex determination system to generate three distinct organismal outcomes from the same genome. Here we investigate the honeybee female and male caste-specific microRNA and transcriptomic molecular signatures during a critical time of larval development. Both previously undetected and novel miRNAs have been discovered, expanding the inventory of these genomic regulators in invertebrates. We show significant differences in the microRNA and transcriptional profiles of diploid females relative to haploid drone males as well as between reproductively distinct females (queens and workers). Queens and drones show gene enrichment in physio-metabolic pathways, whereas workers show enrichment in processes associated with neuronal development, cell signalling and caste biased structural differences. Interestingly, predicted miRNA targets are primarily associated with non-physio-metabolic genes, especially neuronal targets, suggesting a mechanistic disjunction from DNA methylation that regulates physio-metabolic processes. Accordingly, miRNA targets are under-represented in methylated genes. Our data show how a common set of genetic elements are differentially harnessed by an organism, which may provide the remarkable level of developmental flexibility required.

  4. MicroRNAs in Rheumatoid Arthritis

    PubMed Central

    Ceribelli, Angela; Nahid, Md A.; Satoh, Minoru; Chan, Edward K.L.

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic and severe autoimmune disease that affects joint tissues, bone, and cartilage. However, the pathogenesis of RA is still unclear. Autoantibodies such as rheumatoid factor and anti-cyclic citrullinated peptide are useful tools for early diagnosis, monitoring disease activity, and predicting prognosis. Recently, many groups have focused their attention on the role of microRNAs in the pathogenesis of RA, as well as a potential biomarker to monitor RA. In fact, the expression of some microRNAs, such as miR-146a, is upregulated in different cell types and tissues in RA patients. MicroRNAs in RA could also be considered as possible future targets for new therapeutic approaches. PMID:21600203

  5. microRNAs in lupus

    PubMed Central

    ZAN, HONG; TAT, CONNIE; CASALI, PAOLO

    2014-01-01

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of an array of pathogenic autoantibodies, including high-affinity anti-dsDNA IgG antibodies, which plays an important role in disease development and progression. Lupus preferentially affects women during their reproductive years. The pathogenesis of lupus is contributed by both genetic factors and epigenetic modifications that arise from exposure to the environment. Epigenetic marks, including DNA methylation, histone post-translational modifications and microRNAs (miRNAs), interact with genetic programs to regulate immune responses. Epigenetic modifications influence gene expression and modulate B cell functions, such as class switch DNA recombination (CSR), somatic hypermutation (SHM) and plasma cell differentiation, thereby informing the antibody response. Epigenetic dysregulation can result in aberrant antibody responses to exogenous antigens or self-antigens, such as chromatin, histones and dsDNA in lupus. miRNAs play key roles in the post-transcriptional regulation of most gene-regulatory pathways and regulate both the innate and the adaptive immune responses. In mice, dysregulation of miRNAs leads to aberrant immune responses and development of systemic autoimmunity. Altered miRNA expression has been reported in human autoimmune diseases, including lupus. The dysregulation of miRNAs in lupus could be the result of multiple environmental factors, such as sex hormones and viral or bacterial infection. Modulation of miRNA is a potential therapeutic strategy for lupus. PMID:24826805

  6. MicroRNAs and spermatogenesis.

    PubMed

    Kotaja, Noora

    2014-06-01

    In mammals, male gametes are produced inside the testis by spermatogenesis, which has three phases: mitotic proliferation of spermatogonia, meiosis of spermatocytes, and haploid differentiation of spermatids. The genome of male germ cells is actively transcribed to produce phase-specific gene expression patterns. Male germ cells have a complex transcriptome. In addition to protein-coding messenger RNAs, many noncoding RNAs, including microRNAs (miRNAs), are produced. The miRNAs are important regulators of gene expression. They function mainly post-transcriptionally to control the stability or translation of their target messenger RNAs. The miRNAs are expressed in a cell-specific manner during spermatogenesis to participate in the control of each step of male germ cell differentiation. Genetically modified mouse models have demonstrated the importance of miRNA pathways for normal spermatogenesis, and functional studies have been designed to dissect the roles of specific miRNAs in distinct cell types. Clinical studies have exploited the well-defined expression profiles of miRNAs, and human spermatozoal or seminal plasma miRNAs have been explored as potential biomarkers for male factor infertility. This review article discusses the current findings that support the central role of miRNAs in the regulation of spermatogenesis and male fertility.

  7. microRNA and Autism.

    PubMed

    Anitha, Ayyappan; Thanseem, Ismail

    2015-01-01

    Autism is a complex neurodevelopmental disorder characterized by deficiencies in social interaction and communication, and by repetitive and stereotyped behaviors. According to a recent report, the prevalence of this pervasive developmental disorder has risen to 1 in 88. This will have enormous public health implications in the future, and has necessitated the need to discover predictive biomarkers that could index for autism before the onset of symptoms. microRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at the posttranscriptional level. They have recently emerged as prominent epigenetic regulators of various cellular processes including neurodevelopment. They are abundantly present in the brain, and their dysfunction has been implicated in an array of neuropathological conditions including autism. miRNAs, previously known to be expressed only in cells and tissues, have also been detected in extracellular body fluids such as serum, plasma, saliva, and urine. Altered expression of cellular and circulating miRNAs have been observed in autistic individuals compared to healthy controls. miRNAs are now being considered as potential targets for the development of novel therapeutic strategies for autism.

  8. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  9. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  10. Difference in microRNA expression and editing profile of lung tissues from different pig breeds related to immune responses to HP-PRRSV

    PubMed Central

    Li, Jia; Chen, Zhisheng; Zhao, Junlong; Fang, Liurong; Fang, Rui; Xiao, Jiang; Chen, Xing; Zhou, Ao; Zhang, Yingyin; Ren, Liming; Hu, Xiaoxiang; Zhao, Yaofeng; Zhang, Shujun; Li, Ning

    2015-01-01

    Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating diseases for the pig industry. Our goal was to identify microRNAs involved in the host immune response to PRRS. We generated microRNA expression profiles of lung tissues from Tongcheng or Landrace pigs infected with a highly pathogenic PRRS virus (PRRSV) at 3, 5, 7 dpi (day post infection) and control individuals from these two breeds. Our data showed that 278 known and 294 novel microRNAs were expressed in these combined microRNA transcriptomes. Compared with control individuals, almost half of the known microRNAs (116 in Tongcheng and 153 in Landrace) showed significantly differential expression (DEmiRNAs) at least once. The numbers of down-regulated DEmiRNAs were larger than the corresponding number of up-regulated DEmiRNAs in both breeds. Interestingly, miR-2320-5p, which was predicted to bind to conserved sequences of the PRRSV genome, was down-regulated significantly at 3 dpi after PRRSV infection in both breeds. In addition, PRRSV infection induced a significant increase of microRNA editing level in both breeds. Our results provide novel insight into the role of microRNA in response to PRRSV infection in vivo, which will aid the research for developing novel therapies against PRRSV. PMID:25856272

  11. Molecular mechanisms of microRNAs in regulating epithelial-mesenchymal transitions in human cancers.

    PubMed

    Tang, Jinlong; Li, Yuan; Wang, Jingyu; Wen, Zhineng; Lai, Maode; Zhang, Honghe

    2016-02-28

    The epithelial-mesenchymal transition (EMT) provides a strong driving force in the progression of various human cancers and the development of chemoresistance. Recently, numbers of studies have demonstrated that microRNAs (miRNAs), by post-transcriptionally silencing EMT-related molecules, can promote or inhibit the EMT process and play pivotal roles in effectively manipulating the occurrence, development, invasion, and metastasis of cancers. MiRNAs can also control the EMT or be controlled by genetic modification and mutual regulation, especially negative feedback. Therefore, miRNAs can be viewed as either oncogenes or tumor suppressor genes to facilitate or retard the EMT, resulting in far-reaching impact on tumor metastasis and effective diagnosis, treatment, and prognosis.

  12. Diversification and coevolution in brood pollination mutualisms: Windows into the role of biotic interactions in generating biological diversity.

    PubMed

    Hembry, David H; Althoff, David M

    2016-10-01

    Brood pollination mutualisms-interactions in which specialized insects are both the pollinators (as adults) and seed predators (as larvae) of their host plants-have been influential study systems for coevolutionary biology. These mutualisms include those between figs and fig wasps, yuccas and yucca moths, leafflowers and leafflower moths, globeflowers and globeflower flies, Silene plants and Hadena and Perizoma moths, saxifrages and Greya moths, and senita cacti and senita moths. The high reciprocal diversity and species-specificity of some of these mutualisms have been cited as evidence that coevolution between plants and pollinators drives their mutual diversification. However, the mechanisms by which these mutualisms diversify have received less attention. In this paper, we review key hypotheses about how these mutualisms diversify and what role coevolution between plants and pollinators may play in this process. We find that most species-rich brood pollination mutualisms show significant phylogenetic congruence at high taxonomic scales, but there is limited evidence for the processes of both cospeciation and duplication, and there are no unambiguous examples known of strict-sense contemporaneous cospeciation. Allopatric speciation appears important across multiple systems, particularly in the insects. Host-shifts appear to be common, and widespread host-shifts by pollinators may displace other pollinator lineages. There is relatively little evidence for a "coevolution through cospeciation" model or that coevolution promotes speciation in these systems. Although we have made great progress in understanding the mechanisms by which brood pollination mutualisms diversify, many opportunities remain to use these intriguing symbioses to understand the role of biotic interactions in generating biological diversity.

  13. Analytical Calculation of Mutual Information between Weakly Coupled Poisson-Spiking Neurons in Models of Dynamically Gated Communication.

    PubMed

    Cannon, Jonathan

    2017-01-01

    Mutual information is a commonly used measure of communication between neurons, but little theory exists describing the relationship between mutual information and the parameters of the underlying neuronal interaction. Such a theory could help us understand how specific physiological changes affect the capacity of neurons to synaptically communicate, and, in particular, they could help us characterize the mechanisms by which neuronal dynamics gate the flow of information in the brain. Here we study a pair of linear-nonlinear-Poisson neurons coupled by a weak synapse. We derive an analytical expression describing the mutual information between their spike trains in terms of synapse strength, neuronal activation function, the time course of postsynaptic currents, and the time course of the background input received by the two neurons. This expression allows mutual information calculations that would otherwise be computationally intractable. We use this expression to analytically explore the interaction of excitation, information transmission, and the convexity of the activation function. Then, using this expression to quantify mutual information in simulations, we illustrate the information-gating effects of neural oscillations and oscillatory coherence, which may either increase or decrease the mutual information across the synapse depending on parameters. Finally, we show analytically that our results can quantitatively describe the selection of one information pathway over another when multiple sending neurons project weakly to a single receiving neuron.

  14. As you reap, so shall you sow: coupling of harvesting and inoculating stabilizes the mutualism between termites and fungi

    PubMed Central

    Aanen, Duur K

    2006-01-01

    At present there is no consensus theory explaining the evolutionary stability of mutualistic interactions. However, the question is whether there are general ‘rules’, or whether each particular mutualism needs a unique explanation. Here, I address the ultimate evolutionary stability of the ‘agricultural’ mutualism between fungus-growing termites and Termitomyces fungi, and provide a proximate mechanism for how stability is achieved. The key to the proposed mechanism is the within-nest propagation mode of fungal symbionts by termites. The termites suppress horizontal fungal transmission by consuming modified unripe mushrooms (nodules) for food. However, these nodules provide asexual gut-resistant spores that form the inoculum of new substrate. This within-nest propagation has two important consequences: (i) the mutualistic fungi undergo severe, recurrent bottlenecks, so that the fungus is likely to be in monoculture and (ii) the termites ‘artificially’ select for high nodule production, because their fungal food source also provides the inoculum for the next harvest. I also provide a brief comparison of the termite–fungus mutualism with the analogous agricultural mutualism between attine ants and fungi. This comparison shows that—although common factors for the ultimate evolutionary stability of mutualisms can be identified—the proximate mechanisms can be fundamentally different between different mutualisms. PMID:17148364

  15. Prior Knowledge Facilitates Mutual Gaze Convergence and Head Nodding Synchrony in Face-to-face Communication

    PubMed Central

    Thepsoonthorn, C.; Yokozuka, T.; Miura, S.; Ogawa, K.; Miyake, Y.

    2016-01-01

    As prior knowledge is claimed to be an essential key to achieve effective education, we are interested in exploring whether prior knowledge enhances communication effectiveness. To demonstrate the effects of prior knowledge, mutual gaze convergence and head nodding synchrony are observed as indicators of communication effectiveness. We conducted an experiment on lecture task between lecturer and student under 2 conditions: prior knowledge and non-prior knowledge. The students in prior knowledge condition were provided the basic information about the lecture content and were assessed their understanding by the experimenter before starting the lecture while the students in non-prior knowledge had none. The result shows that the interaction in prior knowledge condition establishes significantly higher mutual gaze convergence (t(15.03) = 6.72, p < 0.0001; α = 0.05, n = 20) and head nodding synchrony (t(16.67) = 1.83, p = 0.04; α = 0.05, n = 19) compared to non-prior knowledge condition. This study reveals that prior knowledge facilitates mutual gaze convergence and head nodding synchrony. Furthermore, the interaction with and without prior knowledge can be evaluated by measuring or observing mutual gaze convergence and head nodding synchrony. PMID:27910902

  16. Host sanctions and pollinator cheating in the fig tree–fig wasp mutualism

    PubMed Central

    Jandér, K. Charlotte; Herre, Edward Allen

    2010-01-01

    Theory predicts that mutualisms should be vulnerable to invasion by cheaters, yet mutualistic interactions are both ancient and diverse. What prevents one partner from reaping the benefits of the interaction without paying the costs? Using field experiments and observations, we examined factors affecting mutualism stability in six fig tree–fig wasp species pairs. We experimentally compared the fitness of wasps that did or did not perform their most basic mutualistic service, pollination. We found host sanctions that reduced the fitness of non-pollinating wasps in all derived, actively pollinated fig species (where wasps expend time and energy pollinating), but not in the basal, passively pollinated fig species (where wasps do not). We further screened natural populations of pollinators for wasp individuals that did not carry pollen (‘cheaters’). Pollen-free wasps occurred only in actively pollinating wasp species, and their prevalence was negatively correlated with the sanction strength of their host species. Combined with previous studies, our findings suggest that (i) mutualisms can show coevolutionary dynamics analogous to those of ‘arms races’ in overtly antagonistic interactions; (ii) sanctions are critical for long-term mutualism stability when providing benefits to a host is costly, and (iii) there are general principles that help maintain cooperation both within and among species. PMID:20071379

  17. The mutual events of the uranian satellites in 2006-2010

    NASA Astrophysics Data System (ADS)

    Christou, A. A.

    2005-08-01

    The satellite systems of the giant planets undergo seasons of mutual eclipses and occultations at the planetary equinox. These events provide opportunities for very precise astrometry of the satellites and studies of their physical characteristics that are otherwise possible only in situ by spacecraft. Mutual events of the jovian and saturnian satellites are now observed regularly through dedicated campaigns every 6 and 15 years respectively. Here we expose the upcoming mutual event season of the major uranian satellites Ariel, Umbriel, Titania, Oberon and Miranda, the first to occur since 1966-67 (Christou, Icarus 2005, in press). Approximately 150 mutual eclipses and occultations of these satellites will be observable in the period between Spring 2006 and Spring 2010. We discuss the general characteristics of these events, as compared to similar phenomena in the jovian, saturnian, and Pluto-Charon systems and provide examples. We show how our knowledge of the satellite orbits, albedo variegation across their as-yet-unsurveyed northern hemispheres and possibly the system constants such as the satellite masses and the uranian zonal harmonics will improve considerably through a photometric campaign to observe these events. Finally, we discuss the unique challenges of observing relatively faint satellites near a bright primary and suggest mitigation measures. Astronomy research at the Armagh Observatory is funded by the Northern Ireland Department of Culture, Arts and Leisure (DCAL).

  18. Host sanctions and pollinator cheating in the fig tree-fig wasp mutualism.

    PubMed

    Jandér, K Charlotte; Herre, Edward Allen

    2010-05-22

    Theory predicts that mutualisms should be vulnerable to invasion by cheaters, yet mutualistic interactions are both ancient and diverse. What prevents one partner from reaping the benefits of the interaction without paying the costs? Using field experiments and observations, we examined factors affecting mutualism stability in six fig tree-fig wasp species pairs. We experimentally compared the fitness of wasps that did or did not perform their most basic mutualistic service, pollination. We found host sanctions that reduced the fitness of non-pollinating wasps in all derived, actively pollinated fig species (where wasps expend time and energy pollinating), but not in the basal, passively pollinated fig species (where wasps do not). We further screened natural populations of pollinators for wasp individuals that did not carry pollen ('cheaters'). Pollen-free wasps occurred only in actively pollinating wasp species, and their prevalence was negatively correlated with the sanction strength of their host species. Combined with previous studies, our findings suggest that (i) mutualisms can show coevolutionary dynamics analogous to those of 'arms races' in overtly antagonistic interactions; (ii) sanctions are critical for long-term mutualism stability when providing benefits to a host is costly, and (iii) there are general principles that help maintain cooperation both within and among species.

  19. Negotiation, sanctions, and context dependency in the legume-Rhizobium mutualism.

    PubMed

    Akçay, Erol; Simms, Ellen L

    2011-07-01

    Two important questions about mutualisms are how the fitness costs and benefits to the mutualist partners are determined and how these mechanisms affect the evolutionary dynamics of the mutualism. We tackle these questions with a model of the legume-rhizobium symbiosis that regards the mutualism outcome as a result of biochemical negotiations between the plant and its nodules. We explore the fitness consequences of this mechanism to the plant and rhizobia and obtain four main results. First, negotiations permit the plant to differentially reward more-cooperative rhizobia--a phenomenon termed "plant sanctions"--but only when more-cooperative rhizobia also provide the plant with good outside options during negotiations with other nodules. Second, negotiations may result in seemingly paradoxical cases where the plant is worse off when it has a "choice" between two strains of rhizobia than when infected by either strain alone. Third, even when sanctions are effective, they are by themselves not sufficient to maintain cooperative rhizobia in a population: less cooperative strains always have an advantage at the population level. Finally, partner fidelity feedback, together with genetic correlations between a rhizobium strain's cooperativeness and the outside options it provides, can maintain cooperative rhizobia. Our results show how joint control over the outcome of a mutualism through the proximate mechanism of negotiation can affect the evolutionary dynamics of interspecific cooperation.

  20. Estimating coupling direction between neuronal populations with permutation conditional mutual information.

    PubMed

    Li, Xiaoli; Ouyang, Gaoxiang

    2010-08-15

    To further understand functional connectivity in the brain, we need to identify the coupling direction between neuronal signals recorded from different brain areas. In this paper, we present a novel methodology based on permutation analysis and conditional mutual information for estimation of a directionality index between two neuronal populations. First, the reliability of this method is numerically assessed with a coupled mass neural model; the simulations show that this method is superior to the conditional mutual information method and the Granger causality method for identifying the coupling direction between unidirectional or bidirectional neuronal populations that are generated by the mass neuronal model. The method is also applied to investigate the coupling direction between neuronal populations in CA1 and CA3 in the rat hippocampal tetanus toxin model of focal epilepsy; the propagation direction of the seizure events could be elucidated through this coupling direction estimation method. All together, these results suggest that the permutation conditional mutual information method is a promising technique for estimating directional coupling between mutually interconnected neuronal populations.

  1. SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis

    PubMed Central

    Pulido-Tamayo, Sergio; Weytjens, Bram; De Maeyer, Dries; Marchal, Kathleen

    2016-01-01

    Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result, many cancer driver genes display mutual exclusivity across tumors. However, searching for mutually exclusive gene sets requires analyzing all possible combinations of genes, leading to a problem which is typically too computationally complex to be solved without a stringent a priori filtering, restricting the mutations included in the analysis. To overcome this problem, we present SSA-ME, a network-based method to detect cancer driver genes based on independently scoring small subnetworks for mutual exclusivity using a reinforced learning approach. Because of the algorithmic efficiency, no stringent upfront filtering is required. Analysis of TCGA cancer datasets illustrates the added value of SSA-ME: well-known recurrently mutated but also rarely mutated drivers are prioritized. We show that using mutual exclusivity to detect cancer driver genes is complementary to state-of-the-art approaches. This framework, in which a large number of small subnetworks are being analyzed in order to solve a computationally complex problem (SSA), can be generically applied to any problem in which local neighborhoods in a network hold useful information. PMID:27808240

  2. SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis.

    PubMed

    Pulido-Tamayo, Sergio; Weytjens, Bram; De Maeyer, Dries; Marchal, Kathleen

    2016-11-03

    Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result, many cancer driver genes display mutual exclusivity across tumors. However, searching for mutually exclusive gene sets requires analyzing all possible combinations of genes, leading to a problem which is typically too computationally complex to be solved without a stringent a priori filtering, restricting the mutations included in the analysis. To overcome this problem, we present SSA-ME, a network-based method to detect cancer driver genes based on independently scoring small subnetworks for mutual exclusivity using a reinforced learning approach. Because of the algorithmic efficiency, no stringent upfront filtering is required. Analysis of TCGA cancer datasets illustrates the added value of SSA-ME: well-known recurrently mutated but also rarely mutated drivers are prioritized. We show that using mutual exclusivity to detect cancer driver genes is complementary to state-of-the-art approaches. This framework, in which a large number of small subnetworks are being analyzed in order to solve a computationally complex problem (SSA), can be generically applied to any problem in which local neighborhoods in a network hold useful information.

  3. Insight into temperature-dependent microRNA function in mammalian hibernators

    PubMed Central

    Biggar, Kyle K; Storey, Kenneth B

    2014-01-01

    Mammalian hibernation involves re-programming of metabolic functions, in part, facilitated by microRNA. Although much is known about microRNA function, we lack knowledge on low temperature microRNA target selection. It is possible that the thermodynamics of microRNA target selection could dictate unique temperature-dependent sets of microRNA targets for hibernators. PMID:27582076

  4. Developing microRNA therapeutics: approaching the unique complexities.

    PubMed

    Jackson, Aimee L; Levin, Arthur A

    2012-08-01

    MicroRNAs are endogenous small non-coding RNAs that regulate gene expression by interfering with translation or stability of target transcripts. The importance of microRNAs for maintaining biological functions is illustrated by the fact that microRNAs are exploited in nature to regulate phenotypes, and by the diverse disease phenotypes that result when microRNAs are mutated or improperly expressed. Disease-associated microRNAs might therefore represent a new class of therapeutic targets. With the recent demonstration that inhibition of miR-122 reduces viral load in hepatitis C patients, microRNA modulators are no longer merely theoretical, but rather, have become strong candidate therapeutics. The complexity of microRNA biology offers a novel mechanism of action for therapeutic intervention but also poses unique challenges for the development of therapeutic modulators as drugs.

  5. Mutual diffusion in binary mixtures of ionic liquids and molecular liquids by dynamic light scattering (DLS).

    PubMed

    Rausch, Michael Heinrich; Lehmann, Julia; Leipertz, Alfred; Fröba, Andreas Paul

    2011-05-28

    The present study shows that dynamic light scattering (DLS) is capable of measuring mutual diffusion coefficients for binary mixtures of ionic liquids (ILs) with different molecular liquids over the complete composition range. Evidence is given that the light scattering signals are related to true molecular binary diffusion. The method stands out due to its ability to work non-invasively in macroscopic thermodynamic equilibrium with reasonable accuracy and within convenient measurement periods. Compared with other techniques, mixtures with distinctly higher viscosities can be probed. For exemplary binary mixtures of 1-ethyl-3-methylimidazolium ethylsulfate ([EMIM][EtSO(4)]) with acetone, acetonitrile, dichloromethane, ethanol, or water as well as of 1-ethyl-3-methylimidazolium methanesulfonate ([EMIM][MeSO(3)]) with acetone, water, or methanol, mutual diffusivity data were measured over a wide range of composition at a temperature of 293.15 K. In general, the mutual diffusivity increases with increasing mole fraction of the molecular liquid and similarities to aqueous solutions of classical inorganic salts can be found. The characteristic behavior of the mutual diffusion coefficients is influenced by the nature of the chosen molecular liquid. For IL water mixtures, low light scattering intensities were observed despite the large refractive index difference of the pure components. The reason for this behavior may be the existence of water clusters in the mixtures. Additional measurements for IL acetone mixtures at temperatures ranging from 278.15 K to 323.15 K showed that the temperature dependence of the mutual diffusivity can be represented by Arrhenius functions and is increasing for decreasing mole fractions of acetone.

  6. Secure anonymous mutual authentication for star two-tier wireless body area networks.

    PubMed

    Ibrahim, Maged Hamada; Kumari, Saru; Das, Ashok Kumar; Wazid, Mohammad; Odelu, Vanga

    2016-10-01

    Mutual authentication is a very important service that must be established between sensor nodes in wireless body area network (WBAN) to ensure the originality and integrity of the patient's data sent by sensors distributed on different parts of the body. However, mutual authentication service is not enough. An adversary can benefit from monitoring the traffic and knowing which sensor is in transmission of patient's data. Observing the traffic (even without disclosing the context) and knowing its origin, it can reveal to the adversary information about the patient's medical conditions. Therefore, anonymity of the communicating sensors is an important service as well. Few works have been conducted in the area of mutual authentication among sensor nodes in WBAN. However, none of them has considered anonymity among body sensor nodes. Up to our knowledge, our protocol is the first attempt to consider this service in a two-tier WBAN. We propose a new secure protocol to realize anonymous mutual authentication and confidential transmission for star two-tier WBAN topology. The proposed protocol uses simple cryptographic primitives. We prove the security of the proposed protocol using the widely-accepted Burrows-Abadi-Needham (BAN) logic, and also through rigorous informal security analysis. In addition, to demonstrate the practicality of our protocol, we evaluate it using NS-2 simulator. BAN logic and informal security analysis prove that our proposed protocol achieves the necessary security requirements and goals of an authentication service. The simulation results show the impact on the various network parameters, such as end-to-end delay and throughput. The nodes in the network require to store few hundred bits. Nodes require to perform very few hash invocations, which are computationally very efficient. The communication cost of the proposed protocol is few hundred bits in one round of communication. Due to the low computation cost, the energy consumed by the nodes is

  7. Public-channel cryptography based on mutual chaos pass filters.

    PubMed

    Klein, Einat; Gross, Noam; Kopelowitz, Evi; Rosenbluh, Michael; Khaykovich, Lev; Kinzel, Wolfgang; Kanter, Ido

    2006-10-01

    We study the mutual coupling of chaotic lasers and observe both experimentally and in numeric simulations that there exists a regime of parameters for which two mutually coupled chaotic lasers establish isochronal synchronization, while a third laser coupled unidirectionally to one of the pair does not synchronize. We then propose a cryptographic scheme, based on the advantage of mutual coupling over unidirectional coupling, where all the parameters of the system are public knowledge. We numerically demonstrate that in such a scheme the two communicating lasers can add a message signal (compressed binary message) to the transmitted coupling signal and recover the message in both directions with high fidelity by using a mutual chaos pass filter procedure. An attacker, however, fails to recover an errorless message even if he amplifies the coupling signal.

  8. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses Processing of Applications § 101.45 Mutually... fixed point-to-point microwave applications for authorization under this part will be entitled to...

  9. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses Processing of Applications § 101.45 Mutually... fixed point-to-point microwave applications for authorization under this part will be entitled to...

  10. Nonlinear pattern analysis of ventricular premature beats by mutual information

    NASA Technical Reports Server (NTRS)

    Osaka, M.; Saitoh, H.; Yokoshima, T.; Kishida, H.; Hayakawa, H.; Cohen, R. J.

    1997-01-01

    The frequency of ventricular premature beats (VPBs) has been related to the risk of mortality. However, little is known about the temporal pattern of occurrence of VPBs and its relationship to autonomic activity. Hence, we applied a general correlation measure, mutual information, to quantify how VPBs are generated over time. We also used mutual information to determine the correlation between VPB production and heart rate in order to evaluate effects of autonomic activity on VPB production. We examined twenty subjects with more than 3000 VPBs/day and simulated random time series of VPB occurrence. We found that mutual information values could be used to characterize quantitatively the temporal patterns of VPB generation. Our data suggest that VPB production is not random and VPBs generated with a higher value of mutual information may be more greatly affected by autonomic activity.

  11. Parasponia: a novel system for studying mutualism stability.

    PubMed

    Behm, Jocelyn E; Geurts, Rene; Kiers, E Toby

    2014-12-01

    Understanding how mutualistic interactions are stabilized in the presence of cheaters is a major question in evolutionary biology. The legume-rhizobia mutualism has become a model system for studying how plants control cheating partners. However, the generality and evolutionary origins of these control mechanisms are intensely debated. In this Opinion article, we argue that a novel system--the Parasponia-rhizobia mutualism--will significantly advance research in mutualism stability. Parasponia is the only non-legume lineage to have evolved a rhizobial symbiosis, which provides an evolutionary replicate to test how rhizobial exploitation is controlled. Evidence also suggests that this symbiosis is young. This allows studies at an earlier evolutionary stage in mutualisms, so the origin of control mechanisms can be better understood.

  12. 1. PHOTOCOPY OF ASSOCIATED MUTUAL FIRE INSURANCE MAP 1906: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. PHOTOCOPY OF ASSOCIATED MUTUAL FIRE INSURANCE MAP - 1906: ROGERS LOCOMOTIVE WORKS, PATERSON, N.J. (4x5 NEGATIVE) - Rogers Locomotive & Machine Works, Spruce & Market Streets, Paterson, Passaic County, NJ

  13. Mutual intentions as a causal framework for social groups.

    PubMed

    Noyes, Alexander; Dunham, Yarrow

    2017-02-24

    Children's early emerging intuitive theories are specialized for different conceptual domains. Recently attention has turned to children's concepts of social groups, finding that children believe that many social groups mark uniquely social information such as allegiances and obligations. But another critical component of intuitive theories, the causal beliefs that underlie category membership, has received less attention. We propose that children believe membership in these groups is constituted by mutual intentions: i.e., all group members (including the individual) intend for an individual to be a member and all group members (including the individual) have common knowledge of these intentions. Children in a broad age range (4-9) applied a mutual-intentional framework to newly encountered social groups early in development (Experiment 1, 2, 4). Further, they deploy this mutual-intentional framework selectively, withholding it from essentialized social categories such as gender (Experiment 3). Mutual intentionality appears to be a vital aspect of children's naïve sociology.

  14. 47 CFR 24.831 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 24.831 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS SERVICES Interim Application, Licensing, and Processing Rules for Broadband PCS...) and are timely filed for the same frequency block. (b) Mutually exclusive applications filed on Form...

  15. 47 CFR 24.431 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 24.431 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS SERVICES Interim Application, Licensing and Processing Rules for Narrowband PCS... conflict. (b) Mutually exclusive applications filed on Form 175 for the initial provision of narrowband PCS...

  16. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS § 27.321... Commission's rules governing the Wireless Communications Services involved. The Commission uses the general procedures in this section for processing mutually exclusive applications in the Wireless...

  17. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS § 27.321... Commission's rules governing the Wireless Communications Services involved. The Commission uses the general procedures in this section for processing mutually exclusive applications in the Wireless...

  18. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS § 27.321... Commission's rules governing the Wireless Communications Services involved. The Commission uses the general procedures in this section for processing mutually exclusive applications in the Wireless...

  19. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS § 27.321... Commission's rules governing the Wireless Communications Services involved. The Commission uses the general procedures in this section for processing mutually exclusive applications in the Wireless...

  20. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS § 27.321... Commission's rules governing the Wireless Communications Services involved. The Commission uses the general procedures in this section for processing mutually exclusive applications in the Wireless...

  1. Nonlinear pattern analysis of ventricular premature beats by mutual information

    NASA Technical Reports Server (NTRS)

    Osaka, M.; Saitoh, H.; Yokoshima, T.; Kishida, H.; Hayakawa, H.; Cohen, R. J.

    1997-01-01

    The frequency of ventricular premature beats (VPBs) has been related to the risk of mortality. However, little is known about the temporal pattern of occurrence of VPBs and its relationship to autonomic activity. Hence, we applied a general correlation measure, mutual information, to quantify how VPBs are generated over time. We also used mutual information to determine the correlation between VPB production and heart rate in order to evaluate effects of autonomic activity on VPB production. We examined twenty subjects with more than 3000 VPBs/day and simulated random time series of VPB occurrence. We found that mutual information values could be used to characterize quantitatively the temporal patterns of VPB generation. Our data suggest that VPB production is not random and VPBs generated with a higher value of mutual information may be more greatly affected by autonomic activity.

  2. Comment on ''Mutually unbiased bases, orthogonal Latin squares, and hidden-variable models''

    SciTech Connect

    Hall, Joanne L.; Rao, Asha

    2011-03-15

    In a recent article Paterek, Dakic, and Brukner [Phys. Rev. A 79, 012109 (2009)] show an algorithm for generating mutually unbiased bases from sets of orthogonal Latin squares. They claim that this algorithm works for every set of orthogonal Latin squares. We show that the algorithm only works for particular sets of orthogonal Latin squares. Furthermore, the algorithm is a more readable version of work previously published [Phys. Rev. A 70, 062101 (2004)].

  3. Viscosity and mutual diffusion in strongly asymmetric plasma mixtures

    SciTech Connect

    Bastea, S

    2004-09-07

    The authors present molecular dynamics simulation results for the viscosity and mutual diffusion constant of a strongly asymmetric two-component plasma (TCP). They compare the results with available theoretical models previously tested for much smaller asymmetries. for the case of viscosity they propose a new predictive framework based on the linear mixing rule, while for mutual diffusion they point out some consistency problems of widely used Boltzmann equation based models.

  4. Viscosity and mutual diffusion in strongly asymmetric binary ionic mixtures

    SciTech Connect

    Bastea, Sorin

    2005-05-01

    We present molecular dynamics simulation results for the viscosity and mutual diffusion constant of a strongly asymmetric binary ionic mixture. We compare the results with available theoretical models previously tested for much smaller asymmetries. For the case of viscosity we propose a predictive framework based on the linear mixing rule, while for mutual diffusion we discuss some consistency problems of widely used Boltzmann-equation-based models.

  5. Quantum process reconstruction based on mutually unbiased basis

    SciTech Connect

    Fernandez-Perez, A.; Saavedra, C.; Klimov, A. B.

    2011-05-15

    We study a quantum process reconstruction based on the use of mutually unbiased projectors (MUB projectors) as input states for a D-dimensional quantum system, with D being a power of a prime number. This approach connects the results of quantum-state tomography using mutually unbiased bases with the coefficients of a quantum process, expanded in terms of MUB projectors. We also study the performance of the reconstruction scheme against random errors when measuring probabilities at the MUB projectors.

  6. The mutual shaping of life insurance and medicine in Finland.

    PubMed

    Jauho, Mikko

    2015-08-01

    This article examines the mutual shaping of medicine and private life insurance in Finland before the Second World War. Based on historical texts and archival material, it shows the important effects that the involvement of medicine in client selection for life insurance companies had on medical knowledge and practice. The analysis focuses on the tensions between the main actors in life insurance underwriting--candidates, insurance agents, examining physicians and the central office--as well as the medical examination as the key site of these tensions. The article shows how the introduction of a set of procedural and technical innovations reshaped the medical examination and helped to stabilize the fraught network of life insurance underwriting. These innovations re-scripted medical work. They stressed objective measurable knowledge over the personal skill and clinical acumen of the examining physician, propagated the physical examination and the use of diagnostic technologies and vital standards, multiplied medicine's administrative tasks, and contributed to the introduction of a risk factor approach to medicine. Moreover, the social organization of life insurance promoted the spread of these objects, practices and tasks to other fields of medicine. The case displays how medical innovations are developed through the situated interplay of multiple actors that cuts across the science-society boundary.

  7. Aggressive mimicry coexists with mutualism in an aphid

    PubMed Central

    Salazar, Adrián; Fürstenau, Benjamin; Quero, Carmen; Pérez-Hidalgo, Nicolás; Carazo, Pau; Font, Enrique; Martínez-Torres, David

    2015-01-01

    Understanding the evolutionary transition from interspecific exploitation to cooperation is a major challenge in evolutionary biology. Ant–aphid relationships represent an ideal system to this end because they encompass a coevolutionary continuum of interactions ranging from mutualism to antagonism. In this study, we report an unprecedented interaction along this continuum: aggressive mimicry in aphids. We show that two morphs clonally produced by the aphid Paracletus cimiciformis during its root-dwelling phase establish relationships with ants at opposite sides of the mutualism–antagonism continuum. Although one of these morphs exhibits the conventional trophobiotic (mutualistic) relationship with ants of the genus Tetramorium, aphids of the alternative morph are transported by the ants to their brood chamber and cared for as if they were true ant larvae. Gas chromatography-mass spectrometry analyses reveal that the innate cuticular hydrocarbon profile of the mimic morph resembles the profile of ant larvae more than that of the alternative, genetically identical nonmimic morph. Furthermore, we show that, once in the brood chamber, mimic aphids suck on ant larva hemolymph. These results not only add aphids to the limited list of arthropods known to biosynthesize the cuticular chemicals of their deceived hosts to exploit their resources but describe a remarkable case of plastic aggressive mimicry. The present work adds a previously unidentified dimension to the classical textbook paradigm of aphid–ant relationships by showcasing a complex system at the evolutionary interface between cooperation and exploitation. PMID:25583474

  8. MicroRNA Profiling in Patients with Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy

    PubMed Central

    Popovska-Jankovic, Katerina; Noveski, Predrag; Jankovic-Velickovic, Ljubinka; Stojnev, Slavica; Cukuranovic, Rade; Stefanovic, Vladisav; Toncheva, Draga; Staneva, Rada; Polenakovic, Momir; Plaseska-Karanfilska, Dijana

    2016-01-01

    Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River in the Balkan region. BEN is a chronic tubulointerstitial disease with a slow progression to terminal renal failure and has strong association with upper tract urothelial carcinoma (UTUC). There are several hypotheses about the etiology of BEN, but only the toxic effect of aristolochic acid has been confirmed as a risk factor in the occurrence of the disease. Aberrantly expressed miRNAs have been shown to be associated with many types of cancers. A number of studies have investigated the expression of microRNAs in urothelial carcinoma, mainly on urothelial bladder cancer, and only a few have included patients with UTUC. Here we present the first study of microRNA profiling in UTUC tissues from patients with BEN (BEN-UTUC) and patients with UTUC from nonendemic Balkan regions (non-BEN-UTUC) in comparison to normal kidney tissues. We found 10 miRNAs that were differentially expressed in patients with BEN-UTUC and 15 miRNAs in patients with non-BEN-UTUC. miRNA signature determined in BEN-UTUC patients differs from the non-BEN-UTUC patients; only miR-205-5p was mutual in both groups. PMID:27218105

  9. Non-rigid registration using higher-order mutual information

    NASA Astrophysics Data System (ADS)

    Rueckert, D.; Clarkson, M. J.; Hill, D. L. G.; Hawkes, D. J.

    2000-03-01

    Non-rigid registration of multi-modality images is an important tool for assessing temporal and structural changesbetween images. For rigid registration, voxel similarity measures like mutual information have been shown to alignimages from different modalities accurately and robustly. For non-rigid registration, mutual information can besensitive to local variations of intensity which in MR images may be caused by RF inhomogeneity. The reasonfor the sensitivity of mutual information towards intensity variations stems from the fact that mutual informationignores any spatial information. In this paper we propose an extension of the mutual information framework whichincorporates spatial information about higher-order image structure into the registration process and has the potentialto improve the accuracy and robustness of non-rigid registration in the presence of intensity variations. We haveapplied the non-rigid registration algorithm to a number of simulated MR brain images of a digital phantom whichhave been degraded by a simulated intensity shading and a known deformation. In addition, we have applied thealgorithm for the non-rigid registration of eight pre- and post-operative brain MR images which were acquired withan interventional MR scanner and therefore have substantial intensity shading due to RF field inhomogeneities. Inall cases the second-order estimate of mutual information leads to robust and accurate registration.

  10. Modelling nutritional mutualisms: challenges and opportunities for data integration.

    PubMed

    Clark, Teresa J; Friel, Colleen A; Grman, Emily; Shachar-Hill, Yair; Friesen, Maren L

    2017-09-01

    Nutritional mutualisms are ancient, widespread, and profoundly influential in biological communities and ecosystems. Although much is known about these interactions, comprehensive answers to fundamental questions, such as how resource availability and structured interactions influence mutualism persistence, are still lacking. Mathematical modelling of nutritional mutualisms has great potential to facilitate the search for comprehensive answers to these and other fundamental questions by connecting the physiological and genomic underpinnings of mutualisms with ecological and evolutionary processes. In particular, when integrated with empirical data, models enable understanding of underlying mechanisms and generalisation of principles beyond the particulars of a given system. Here, we demonstrate how mathematical models can be integrated with data to address questions of mutualism persistence at four biological scales: cell, individual, population, and community. We highlight select studies where data has been or could be integrated with models to either inform model structure or test model predictions. We also point out opportunities to increase model rigour through tighter integration with data, and describe areas in which data is urgently needed. We focus on plant-microbe systems, for which a wealth of empirical data is available, but the principles and approaches can be generally applied to any nutritional mutualism. © 2017 John Wiley & Sons Ltd/CNRS.

  11. A novel obligate cultivation mutualism between damselfish and Polysiphonia algae.

    PubMed

    Hata, Hiroki; Kato, Makoto

    2006-12-22

    In cultivation mutualisms, farming animals prepare fields for cultivars, enhance their growth and harvest them. For example, in terrestrial ecosystems, plant-herbivore cultivation mutualisms arose between humans and their crops only relatively recently. We discovered an obligate cultivation mutualism between a damselfish and an alga in a coral reef ecosystem. The damselfish, Stegastes nigricans, manages algal farms through territorial defence against the invading grazers and through weeding of unpalatable algae. As a result, the algal farms of S. nigricans are dominated by one species, Polysiphonia sp. We performed an exhaustive survey of algal assemblages inside and outside the territories of five damselfish species around the Ryukyu Islands, Japan, using molecular and morphological characteristics. Polysiphonia sp. 1 grew exclusively inside the farms of S. nigricans, and never elsewhere. Since only Polysiphonia sp. 1 is harvested and consumed by the damselfish as a staple food, this interdependent relationship is an obligate cultivation mutualism. This is the first record of an obligate plant-herbivore cultivation mutualism in a marine ecosystem. Our data also suggest that three other Polysiphonia species are facultatively mutual with, commensal with, or parasitic on other damselfish species.

  12. A novel obligate cultivation mutualism between damselfish and Polysiphonia algae

    PubMed Central

    Hata, Hiroki; Kato, Makoto

    2006-01-01

    In cultivation mutualisms, farming animals prepare fields for cultivars, enhance their growth and harvest them. For example, in terrestrial ecosystems, plant–herbivore cultivation mutualisms arose between humans and their crops only relatively recently. We discovered an obligate cultivation mutualism between a damselfish and an alga in a coral reef ecosystem. The damselfish, Stegastes nigricans, manages algal farms through territorial defence against the invading grazers and through weeding of unpalatable algae. As a result, the algal farms of S. nigricans are dominated by one species, Polysiphonia sp. We performed an exhaustive survey of algal assemblages inside and outside the territories of five damselfish species around the Ryukyu Islands, Japan, using molecular and morphological characteristics. Polysiphonia sp. 1 grew exclusively inside the farms of S. nigricans, and never elsewhere. Since only Polysiphonia sp. 1 is harvested and consumed by the damselfish as a staple food, this interdependent relationship is an obligate cultivation mutualism. This is the first record of an obligate plant–herbivore cultivation mutualism in a marine ecosystem. Our data also suggest that three other Polysiphonia species are facultatively mutual with, commensal with, or parasitic on other damselfish species. PMID:17148297

  13. An invasive plant-fungal mutualism reduces arthropod diversity.

    PubMed

    Rudgers, Jennifer A; Clay, Keith

    2008-08-01

    Ecological theory holds that competition and predation are the most important biotic forces affecting the composition of communities. Here, we expand this framework by demonstrating that mutualism can fundamentally alter community and food web structure. In large, replicated field plots, we manipulated the mutualism between a dominant plant (Lolium arundinaceum) and symbiotic fungal endophyte (Neotyphodium coenophialum). The presence of the mutualism reduced arthropod abundance up to 70%, reduced arthropod diversity nearly 20%, shifted arthropod species composition relative to endophyte-free plots and suppressed the biomass and richness of other plant species in the community. Herbivorous arthropods were more strongly affected than carnivores, and for both herbivores and carnivores, effects of the mutualism appeared to propagate indirectly via organisms occurring more basally in the food web. The influence of the mutualism was as great or greater than previously documented effects of competition and predation on arthropod communities. Our work demonstrates that a keystone mutualism can significantly reduce arthropod biodiversity at a broad community scale.

  14. Spectral image analysis of mutual illumination between florescent objects.

    PubMed

    Tominaga, Shoji; Kato, Keiji; Hirai, Keita; Horiuchi, Takahiko

    2016-08-01

    This paper proposes a method for modeling and component estimation of the spectral images of the mutual illumination phenomenon between two fluorescent objects. First, we briefly describe the bispectral characteristics of a single fluorescent object, which are summarized as a Donaldson matrix. We suppose that two fluorescent objects with different bispectral characteristics are located close together under a uniform illumination. Second, we model the mutual illumination between two objects. It is shown that the spectral composition of the mutual illumination is summarized with four components: (1) diffuse reflection, (2) diffuse-diffuse interreflection, (3) fluorescent self-luminescence, and (4) interreflection by mutual fluorescent illumination. Third, we develop algorithms for estimating the spectral image components from the observed images influenced by the mutual illumination. When the exact Donaldson matrices caused by the mutual illumination influence are unknown, we have to solve a non-linear estimation problem to estimate both the spectral functions and the location weights. An iterative algorithm is then proposed to solve the problem based on the alternate estimation of the spectral functions and the location weights. In our experiments, the feasibility of the proposed method is shown in three cases: the known Donaldson matrices, weak interreflection, and strong interreflection.

  15. Signal-on fluorescence biosensor for microRNA-21 detection based on DNA strand displacement reaction and Mg(2+)-dependent DNAzyme cleavage.

    PubMed

    Yin, Huan-Shun; Li, Bing-Chen; Zhou, Yun-Lei; Wang, Hai-Yan; Wang, Ming-Hui; Ai, Shi-Yun

    2017-10-15

    MicroRNAs have been involved into many biological processes and are regarded as disease biomarkers. Simple, rapid, sensitive and selective method for microRNA detection is crucial for early diagnosis and therapy of diseases. In this work, sensitive fluorescence assay was developed for microRNA-21 detection based on DNA polymerase induced strand displacement amplification reaction, Mg(2+)-dependent DNAzyme catalysis reaction, and magnetic separation. In the presence of target microRNA-21, amounts of trigger DNA could be produced with DNA polymerase induced strand displacement amplification reaction, and the trigger DNA could be further hybridized with signal DNA, which was labeled with biotin and AMCA dye. After introduction of Mg(2+), trigger DNA could form DNAzyme to cleave signal DNA. After magnetic separation, the DNA fragment with AMCA dye could give fluorescence signal, which was related to microRNA-21 concentration. Based on the two efficient signal amplifications, the developed method showed high detection sensitivity with low detection limit of 0.27fM (3σ). In addition, this fluorescence strategy also possessed excellent detection specificity, and could be applied to analyze microRNA-21 expression level in serum of cancer patient. According to the obtained results, the developed fluorescence method might be a promising detection platform for microRNA-21 quantitative analysis in biomedical research and clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. MicroRNA regulation in heart and skeletal muscle over the freeze-thaw cycle in the freeze tolerant wood frog.

    PubMed

    Bansal, Saumya; Luu, Bryan E; Storey, Kenneth B

    2016-02-01

    The North American wood frog, Rana sylvatica, is one of just a few anuran species that tolerates whole body freezing during the winter and has been intensely studied to identify the biochemical adaptations that support freeze tolerance. Among these adaptations is the altered expression of many genes, making freeze-responsive changes to gene regulatory mechanisms a topic of interest. The present study focuses on the potential involvement of microRNAs as one such regulatory mechanism and aims to better understand freeze/thaw stress-induced microRNA responses in the freeze-tolerant wood frog. Using quantitative PCR, relative levels of 53 microRNAs were measured in heart and skeletal muscle of control, 24 h frozen, and 8 h thawed frogs. MicroRNAs showed tissue specific expression patterns: 21 microRNAs decreased in the heart during thawing, whereas 16 microRNAs increased during freezing stress in skeletal muscle. These findings suggest that select genes may be activated and suppressed in heart and skeletal muscle, respectively, in response to freezing. Bioinformatics analysis using the DIANA miRPath program (v.2.0) predicted that the differentially expressed microRNAs may collectively regulate tissue-specific cellular pathways to promote survival of wood frogs undergoing freezing and thawing.

  17. Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C patients.

    PubMed

    Wang, Jiang-hua; Jiang, Dong; Rao, Hui-yng; Zhao, Jing-min; Wang, Yu; Wei, Lai

    2015-01-01

    MicroRNA-122 has been shown to be crucial for efficient HCV RNA replication in vitro. Pretreatment intrahepatic microRNA-122 levels in chronic hepatitis C (CHC) patients have been associated with the outcomes of interferon therapy. Here, we determined microRNA-122 serum levels in CHC patients and healthy donors using an absolute quantification approach and evaluated the correlation with liver inflammation grades and serum alanine aminotransferase (ALT) levels. Serum samples were collected from 105 treatment-naive CHC patients, 11 acute hepatitis patients, and 33 healthy donors. Serum microRNA-122 was measured using the TaqMan RT-qPCR. The cycle threshold values were converted to copy numbers by drawing a standard curve using a chemical synthetic standard. For accurate quantification, copy numbers were further normalized according to the recovery ratios of spiked-in cel-miR-39. Serum levels of microRNA-122 were significantly higher in acute hepatitis and CHC patients than in healthy donors (p<0.001). However, there was no significant association between microRNA-122 and ALT serum levels or liver inflammation grades. The present study showed that serum microRNA-122 was elevated in acute and chronic hepatitis patients. However, this biomarker for acute liver injury did not reflect the liver inflammation activity in CHC patients. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. No Evidence of Emotional Dysregulation or Aversion to Mutual Gaze in Preschoolers with Autism Spectrum Disorder: An Eye-Tracking Pupillometry Study.

    PubMed

    Nuske, Heather J; Vivanti, Giacomo; Dissanayake, Cheryl

    2015-11-01

    The 'gaze aversion hypothesis', suggests that people with Autism Spectrum Disorder (ASD) avoid mutual gaze because they experience it as hyper-arousing. To test this hypothesis we showed mutual and averted gaze stimuli to 23 mixed-ability preschoolers with ASD (M Mullen DQ = 68) and 21 typically-developing preschoolers, aged 2-5 years, using eye-tracking technology to measure visual attention and emotional arousal (i.e., pupil dilation). There were no group differences in attention to the eye region or pupil dilation. Both groups dilated their pupils more to mutual compared to averted gaze. More internalizing symptoms in the children with ASD related to less emotional arousal to mutual gaze. The pattern of results suggests that preschoolers with ASD are not dysregulated in their responses to mutual gaze.

  19. Isolation and characterization of vesicular and non-vesicular microRNAs circulating in sera of partially hepatectomized rats

    PubMed Central

    Castoldi, Mirco; Kordes, Claus; Sawitza, Iris; Häussinger, Dieter

    2016-01-01

    Circulating microRNAs are protected from degradation by their association with either vesicles or components of the RNAi machinery. Although increasing evidence indicates that cell-free microRNAs are transported in body fluids by different types of vesicles, current research mainly focuses on the characterization of exosome-associated microRNAs. However, as isolation and characterization of exosomes is challenging, it is yet unclear whether exosomes or other vesicular elements circulating in serum are the most reliable source for discovering disease-associated biomarkers. In this study, circulating microRNAs associated to the vesicular and non-vesicular fraction of sera isolated from partially hepatectomized rats were measured. Here we show that independently from their origin, levels of miR-122, miR-192, miR-194 and Let-7a are up-regulated two days after partial hepatectomy. The inflammation-associated miR-150 and miR-155 are up-regulated in the vesicular-fraction only, while the regeneration-associated miR-21 and miR-33 are up-regulated in the vesicular- and down-regulated in the non-vesicular fraction. Our study shows for the first time the modulation of non-vesicular microRNAs in animals recovering from partial hepatectomy, suggesting that, in the search for novel disease-associated biomarkers, the profiling of either vesicular or non-vesicular microRNAs may be more relevant than the analysis of microRNAs isolated from unfractionated serum. PMID:27535708

  20. MicroRNA sequencing and molecular mechanisms analysis of the effects of gold nanoparticles on human dermal fibroblasts.

    PubMed

    Huang, Yan; Lü, Xiaoying; Qu, Yinghua; Yang, Yamin; Wu, Si

    2015-01-01

    The aim of this study is to investigate the mechanism of the effects of gold nanoparticles (GNPs) on human dermal fibroblasts (HDFs) at the microRNA level. First, 20-nm GNPs were synthesized and their effect on HDF proliferation was assayed. SOLiD sequencing technology was then utilized to obtain the microRNA expression profile after GNP treatment. The microRNA expression data were compared with previously obtained mRNA and protein expression data to identify the microRNA target mRNAs/proteins. Moreover, bioinformatics analyses and validation experiments were conducted. Lastly, the roles of GNPs and silver nanoparticle (SNPs) on HDFs were compared at the microRNA level. The results showed that GNPs were not cytotoxic as 202 microRNAs were differentially expressed after treatment with 200 μm GNPs for 1, 4 and 8 h. Bioinformatics analyses revealed that these dysregulated miRNAs mainly functioned in metabolic processes and participated in 71 biological pathways, including two key pathways in which the differentially expressed miRNA, target mRNAs and proteins were simultaneously joined, the mRNA processing pathway and MAPK signaling pathway. Biological experiments in cells confirmed that GNPs affected energy metabolism but did not induce apoptosis, destroy the cytoskeleton or induce reactive oxygen species (ROS) production. Comparing the mechanism of the effects of GNPs and SNPs on HDFs at the microRNA level, it was found that, unlike SNPs, GNPs impacted the cell cycle, weakened the ATP synthesis inhibition and cytoskeleton damage, suppressed apoptosis, and did not lead to cytotoxicity. The difference in ROS production by these two nanoparticles might partially explain the fact that GNPs showed no cytotoxic effects on HDFs, unlike SNPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  2. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  3. Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Maes, Olivier C.; Xu, Suying; Hada, Megumi; Wu, Honglu; Wang, Eugenia

    2007-01-01

    Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2

  4. Modulation of microrna in two genetically disparate chicken lines showing different necrotic enteritis disease susceptibility

    USDA-ARS?s Scientific Manuscript database

    Necrotic enteritis (NE) is a re-emerging disease as a result of an increased restriction on the use of antibiotics in poultry. However, the molecular mechanisms underlying the pathology of NE are unclear. Therefore, we carried out small RNA transcriptome analysis in an experimentally induced NE m...

  5. Exploring the mutual enhancement between droughts and heatwaves in Europe

    NASA Astrophysics Data System (ADS)

    Samaniego, L. E.; Kumar, R.; Thober, S.; Pan, M.; Prudhomme, C.; Sheffield, J.; Wanders, N.; Wood, E. F.

    2016-12-01

    Extensive analyses of past and future changes in essential hydrologicalvariables such as soil moisture based on climate and/or land surfacemodel projections have been carried out during the last decades. Recentstudies, however, showed that no comprehensive picture of theanticipated changes has evolved basically due to the large uncertaintiesin both observed and projected changes as well as their coarser spatialresolution. So far, concluding statements cannot be drawn, in particularfor droughts and heat waves, although the key role of soil moisture foramplifying heat waves and its skill for predicting temperature has beenidentified. In this study, we hypothesized that the mutual enhancementbetween droughts and heat waves is intensified as the climate warms. Putdifferently, a drought can make a hot day hotter while a heat wave canexacerbate a moderate drought event into an extreme one. Europe, in particular, has endured large scale drought-heat-wave eventsduring the recent past (e.g., 2003), which have induced enormoussocio-economic losses as well as casualties. Testing thepreviously posed hypothesis within the Pan-EU domain has been limitedmainly by the availability of reliable and high-resolution data sets. The EDgE project commissioned by the ECMWF (C3S) provides a uniqueopportunity to test this hypothesis. High-resolution multi-modelhydrologic simulations over the Pan-EU domain at a scale of 5x5 km2 havebeen completed for the historical period 1955-2015 with the mHM(www.ufz.de/mhm) and PCR-GLOBWB. Noah-MP and VIC simulations will beaccomplished soon. Using these multi-model unprecedented simulations, daily soil moistureindex and temperature anomalies from 1955 to 2015 will beestimated. The stochastic relationships between these variables will beinvestigated with empirical copulas. The main goal of this study is totest whether a significant Granger causality existsbetween soil moisture and temperature anomaly fields over thePan-EU. The advantage of this testing

  6. MicroRNAs in skin tissue engineering.

    PubMed

    Miller, Kyle J; Brown, David A; Ibrahim, Mohamed M; Ramchal, Talisha D; Levinson, Howard

    2015-07-01

    35.2 million annual cases in the U.S. require clinical intervention for major skin loss. To meet this demand, the field of skin tissue engineering has grown rapidly over the past 40 years. Traditionally, skin tissue engineering relies on the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a three-dimensional substrate matrix, or scaffold, and exposed to the proper molecular, physical, and/or electrical signals to encourage growth and differentiation. However, clinically available bioengineered skin equivalents (BSEs) suffer from a number of drawbacks, including time required to generate autologous BSEs, poor allogeneic BSE survival, and physical limitations such as mass transfer issues. Additionally, different types of skin wounds require different BSE designs. MicroRNA has recently emerged as a new and exciting field of RNA interference that can overcome the barriers of BSE design. MicroRNA can regulate cellular behavior, change the bioactive milieu of the skin, and be delivered to skin tissue in a number of ways. While it is still in its infancy, the use of microRNAs in skin tissue engineering offers the opportunity to both enhance and expand a field for which there is still a vast unmet clinical need. Here we give a review of skin tissue engineering, focusing on the important cellular processes, bioactive mediators, and scaffolds. We further discuss potential microRNA targets for each individual component, and we conclude with possible future applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. microRNA in Human Reproduction.

    PubMed

    Eisenberg, Iris; Kotaja, Noora; Goldman-Wohl, Debra; Imbar, Tal

    2015-01-01

    microRNAs constitute a large family of approximately 21-nucleotide-long, noncoding RNAs. They emerged more than 20 years ago as key posttranscriptional regulators of gene expression. The regulatory role of these small RNA molecules has recently begun to be explored in the human reproductive system. microRNAs have been shown to play an important role in control of reproductive functions, especially in the processes of oocyte maturation, folliculogenesis, corpus luteum function, implantation, and early embryonic development. Knockout of Dicer, the cytoplasmic enzyme that cleaves the pre-miRNA to its mature form, results in postimplantation embryonic lethality in several animal models, attributing to these small RNA vital functions in reproduction and development. Another intriguing characteristic of microRNAs is their presence in body fluids in a remarkably stable form that is protected from endogenous RNase activity. In this chapter we will describe the current knowledge on microRNAs, specifically relating to human gonadal cells. We will focus on their role in the ovarian physiologic process and ovulation dysfunction, regulation of spermatogenesis and male fertility, and putative involvement in human normal and aberrant trophoblast differentiation and invasion through the process of placentation.

  8. MicroRNAs in Thyroid Cancer

    PubMed Central

    2011-01-01

    Context: Traditionally, factors predisposing to diseases are either genetic (“nature”) or environmental, also known as lifestyle-related (“nurture”). Papillary thyroid cancer is an example of a disease where the respective roles of these factors are surprisingly unclear. Evidence Acquisition: Original articles and reviews summarizing our current understanding of the role of microRNA in thyroid tumorigenesis are reviewed and evaluated. Conclusion: The genetic predisposition to papillary thyroid cancer appears to consist of a variety of gene mutations that are mostly either of low penetrance and common or of high penetrance but rare. Moreover, they likely interact with each other and with environmental factors. The culpable genes may not be of the traditional, protein-coding type. A limited number of noncoding candidate genes have indeed been described, and we propose here that the failure to find mutations in traditional protein-coding genes is not coincidental. Instead, a more likely hypothesis is that changes in the expression of multiple regulatory RNA genes, e.g. microRNAs, may be a major mechanism. Our review of the literature strongly supports this notion in that a polymorphism in one microRNAs (miR-146a) predisposes to thyroid carcinoma, whereas numerous other microRNAs are involved in signaling (mainly PTEN/PI3K/AKT and T3/THRB) that is central to thyroid carcinogenesis. PMID:21865360

  9. Novel microRNA families expanded in the human genome.

    PubMed

    Du, Zhi-Qiang; Yang, Cai-Xia; Rothschild, Max F; Ross, Jason W

    2013-02-12

    Most studies on the origin and evolution of microRNA in the human genome have been focused on its relationship with repetitive elements and segmental duplications. However, duplication events at a smaller scale (<1 kb) could also contribute to microRNA expansion, as demonstrated in this study. Using comparative genome analysis and bioinformatics methods, we found nine novel expanded microRNA families enriched in short duplicated sequences in the human genome. Furthermore, novel genomic regions were found to contain microRNA paralogs for microRNA families previously analyzed to be related to segmental duplications. We found that for microRNA families expanded in the human genome, 14 families are specific to the primate lineage, and nine are non-specific, respectively. Two microRNA families (hsa-mir-1233 and hsa-mir-622) appear to be further expanded in the human genome, and were confirmed by fluorescence in situ hybridization. These novel microRNA families expanded in the human genome were mostly embedded in or close to proteins with conserved functions. Furthermore, besides the Alu element, L1 elements could also contribute to the origination of microRNA paralog families. Together, we found that small duplication events could also contribute to microRNA expansion, which could provide us novel insights on the evolution of human genome structure and function.

  10. Staufen Negatively Modulates MicroRNA Activity in Caenorhabditis elegans

    PubMed Central

    Ren, Zhiji; Veksler-Lublinsky, Isana; Morrissey, David; Ambros, Victor

    2016-01-01

    The double-stranded RNA-binding protein Staufen has been implicated in various posttranscriptional gene regulatory processes. Here, we demonstrate that the Caenorhabditis elegans homolog of Staufen, STAU-1, functionally interacts with microRNAs. Loss-of-function mutations of stau-1 significantly suppress phenotypes of let-7 family microRNA mutants, a hypomorphic allele of dicer, and a lsy-6 microRNA partial loss-of-function mutant. Furthermore, STAU-1 modulates the activity of lin-14, a target of lin-4 and let-7 family microRNAs, and this modulation is abolished when the 3′ untranslated region of lin-14 is removed. Deep sequencing of small RNA cDNA libraries reveals no dramatic change in the levels of microRNAs or other small RNA populations between wild-type and stau-1 mutants, with the exception of certain endogenous siRNAs in the WAGO pathway. The modulation of microRNA activity by STAU-1 does not seem to be associated with the previously reported enhanced exogenous RNAi (Eri) phenotype of stau-1 mutants, since eri-1 exhibits the opposite effect on microRNA activity. Altogether, our results suggest that STAU-1 negatively modulates microRNA activity downstream of microRNA biogenesis, possibly by competing with microRNAs for binding on the 3′ untranslated region of target mRNAs. PMID:26921297

  11. microRNA target prediction programs predict many false positives.

    PubMed

    Pinzón, Natalia; Li, Blaise; Martinez, Laura; Sergeeva, Anna; Presumey, Jessy; Apparailly, Florence; Seitz, Hervé

    2017-02-01

    According to the current view, each microRNA regulates hundreds of genes. Computational tools aim at identifying microRNA targets, usually selecting evolutionarily conserved microRNA binding sites. While the false positive rates have been evaluated for some prediction programs, that information is rarely put forward in studies making use of their predictions. Here, we provide evidence that such predictions are often biologically irrelevant. Focusing on miR-223-guided repression, we observed that it is often smaller than inter-individual variability in gene expression among wild-type mice, suggesting that most predicted targets are functionally insensitive to that microRNA. Furthermore, we found that human haplo-insufficient genes tend to bear the most highly conserved microRNA binding sites. It thus appears that biological functionality of microRNA binding sites depends on the dose-sensitivity of their host gene and that, conversely, it is unlikely that every predicted microRNA target is dose-sensitive enough to be functionally regulated by microRNAs. We also observed that some mRNAs can efficiently titrate microRNAs, providing a reason for microRNA binding site conservation for inefficiently repressed targets. Finally, many conserved microRNA binding sites are conserved in a microRNA-independent fashion: Sequence elements may be conserved for other reasons, while being fortuitously complementary to microRNAs. Collectively, our data suggest that the role of microRNAs in normal and pathological conditions has been overestimated due to the frequent overlooking of false positive rates. © 2017 Pinzón et al.; Published by Cold Spring Harbor Laboratory Press.

  12. microRNA target prediction programs predict many false positives

    PubMed Central

    Pinzón, Natalia; Martinez, Laura; Sergeeva, Anna; Presumey, Jessy; Apparailly, Florence

    2017-01-01

    According to the current view, each microRNA regulates hundreds of genes. Computational tools aim at identifying microRNA targets, usually selecting evolutionarily conserved microRNA binding sites. While the false positive rates have been evaluated for some prediction programs, that information is rarely put forward in studies making use of their predictions. Here, we provide evidence that such predictions are often biologically irrelevant. Focusing on miR-223-guided repression, we observed that it is often smaller than inter-individual variability in gene expression among wild-type mice, suggesting that most predicted targets are functionally insensitive to that microRNA. Furthermore, we found that human haplo-insufficient genes tend to bear the most highly conserved microRNA binding sites. It thus appears that biological functionality of microRNA binding sites depends on the dose-sensitivity of their host gene and that, conversely, it is unlikely that every predicted microRNA target is dose-sensitive enough to be functionally regulated by microRNAs. We also observed that some mRNAs can efficiently titrate microRNAs, providing a reason for microRNA binding site conservation for inefficiently repressed targets. Finally, many conserved microRNA binding sites are conserved in a microRNA-independent fashion: Sequence elements may be conserved for other reasons, while being fortuitously complementary to microRNAs. Collectively, our data suggest that the role of microRNAs in normal and pathological conditions has been overestimated due to the frequent overlooking of false positive rates. PMID:28148562

  13. Indirect defense in a highly specific ant-plant mutualism.

    PubMed

    Grangier, Julien; Dejean, Alain; Malé, Pierre-Jean G; Orivel, Jérôme

    2008-10-01

    Although associations between myrmecophytes and their plant ants are recognized as a particularly effective form of protective mutualism, their functioning remains incompletely understood. This field study examined the ant-plant Hirtella physophora and its obligate ant associate Allomerus decemarticulatus. We formulated two hypotheses on the highly specific nature of this association: (1) Ant presence should be correlated with a marked reduction in the amount of herbivory on the plant foliage; (2) ant activity should be consistent with the "optimal defense" theory predicting that the most vulnerable and valuable parts of the plant are the best defended. We validated the first hypothesis by demonstrating that for ant-excluded plants, expanding leaves, but also newly matured ones in the long term, suffered significantly more herbivore damage than ant-inhabited plants. We showed that A. decemarticulatus workers represent both constitutive and inducible defenses for their host, by patrolling its foliage and rapidly recruiting nestmates to foliar wounds. On examining how these activities change according to the leaves' developmental stage, we found that the number of patrolling ants dramatically decreased as the leaves matured, while leaf wounds induced ant recruitment regardless of the leaf's age. The resulting level of these indirect defenses was roughly proportional to leaf vulnerability and value during its development, thus validating our second hypothesis predicting optimal protection. This led us to discuss the factors influencing ant activity on the plant's surface. Our study emphasizes the importance of studying both the constitutive and inducible components of indirect defense when evaluating its efficacy and optimality.

  14. Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate.

    PubMed

    Giacometti, Simone; Benbahouche, Nour El Houda; Domanski, Michal; Robert, Marie-Cécile; Meola, Nicola; Lubas, Michal; Bukenborg, Jakob; Andersen, Jens S; Schulze, Wiebke M; Verheggen, Celine; Kudla, Grzegorz; Jensen, Torben Heick; Bertrand, Edouard

    2017-03-14

    The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3'-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3'-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis.

  15. NSECT sinogram sampling optimization by normalized mutual information

    NASA Astrophysics Data System (ADS)

    Viana, Rodrigo S.; Galarreta-Valverde, Miguel A.; Mekkaoui, Choukri; Yoriyaz, Hélio; Jackowski, Marcel P.

    2015-03-01

    Neutron Stimulated Emission Computed Tomography (NSECT) is an emerging noninvasive imaging technique that measures the distribution of isotopes from biological tissue using fast-neutron inelastic scattering reaction. As a high-energy neutron beam illuminates the sample, the excited nuclei emit gamma rays whose energies are unique to the emitting nuclei. Tomographic images of each element in the spectrum can then be reconstructed to represent the spatial distribution of elements within the sample using a first generation tomographic scan. NSECT's high radiation dose deposition, however, requires a sampling strategy that can yield maximum image quality under a reasonable radiation dose. In this work, we introduce an NSECT sinogram sampling technique based on the Normalized Mutual Information (NMI) of the reconstructed images. By applying the Radon Transform on the ground-truth image obtained from a carbon-based synthetic phantom, different NSECT sinogram configurations were simulated and compared by using the NMI as a similarity measure. The proposed methodology was also applied on NSECT images acquired using MCNP5 Monte Carlo simulations of the same phantom to validate our strategy. Results show that NMI can be used to robustly predict the quality of the reconstructed NSECT images, leading to an optimal NSECT acquisition and a minimal absorbed dose by the patient.

  16. Temperature dependences of rate coefficients for electron catalyzed mutual neutralization.

    PubMed

    Shuman, Nicholas S; Miller, Thomas M; Friedman, Jeffrey F; Viggiano, Albert A; Maeda, Satoshi; Morokuma, Keiji

    2011-07-14

    The flowing afterglow technique of variable electron and neutral density attachment mass spectrometry (VENDAMS) has recently yielded evidence for a novel plasma charge loss process, electron catalyzed mutual neutralization (ECMN), i.e., A(+) + B(-) + e(-) → A + B + e(-). Here, rate constants for ECMN of two polyatomic species (POCl(3)(-) and POCl(2)(-)) and one diatomic species (Br(2)(-)) each with two monatomic cations (Ar(+)and Kr(+)) are measured using VENDAMS over the temperature range 300 K-500 K. All rate constants show a steep negative temperature dependence, consistent with that expected for a three body process involving two ions and an electron. No variation in rate constants as a function of the cation type is observed outside of uncertainty; however, rate constants of the polyatomic anions (~1 × 10(-18) cm(6) s(-1) at 300 K) are measurably higher than that for Br(2)(-) [(5.5 ± 2) × 10(-19) cm(6) s(-1) at 300 K].

  17. Temperature dependences of rate coefficients for electron catalyzed mutual neutralization

    SciTech Connect

    Shuman, Nicholas S.; Miller, Thomas M.; Friedman, Jeffrey F.; Viggiano, Albert A.; Maeda, Satoshi; Morokuma, Keiji

    2011-07-14

    The flowing afterglow technique of variable electron and neutral density attachment mass spectrometry (VENDAMS) has recently yielded evidence for a novel plasma charge loss process, electron catalyzed mutual neutralization (ECMN), i.e., A{sup +}+ B{sup -}+ e{sup -}{yields} A + B + e{sup -}. Here, rate constants for ECMN of two polyatomic species (POCl{sub 3}{sup -} and POCl{sub 2}{sup -}) and one diatomic species (Br{sub 2}{sup -}) each with two monatomic cations (Ar{sup +}and Kr{sup +}) are measured using VENDAMS over the temperature range 300 K-500 K. All rate constants show a steep negative temperature dependence, consistent with that expected for a three body process involving two ions and an electron. No variation in rate constants as a function of the cation type is observed outside of uncertainty; however, rate constants of the polyatomic anions ({approx}1 x 10{sup -18} cm{sup 6} s{sup -1} at 300 K) are measurably higher than that for Br{sub 2}{sup -}[(5.5 {+-} 2) x 10{sup -19} cm{sup 6} s{sup -1} at 300 K].

  18. Mutual information-based feature selection for radiomics

    NASA Astrophysics Data System (ADS)

    Oubel, Estanislao; Beaumont, Hubert; Iannessi, Antoine

    2016-03-01

    Background The extraction and analysis of image features (radiomics) is a promising field in the precision medicine era, with applications to prognosis, prediction, and response to treatment quantification. In this work, we present a mutual information - based method for quantifying reproducibility of features, a necessary step for qualification before their inclusion in big data systems. Materials and Methods Ten patients with Non-Small Cell Lung Cancer (NSCLC) lesions were followed over time (7 time points in average) with Computed Tomography (CT). Five observers segmented lesions by using a semi-automatic method and 27 features describing shape and intensity distribution were extracted. Inter-observer reproducibility was assessed by computing the multi-information (MI) of feature changes over time, and the variability of global extrema. Results The highest MI values were obtained for volume-based features (VBF). The lesion mass (M), surface to volume ratio (SVR) and volume (V) presented statistically significant higher values of MI than the rest of features. Within the same VBF group, SVR showed also the lowest variability of extrema. The correlation coefficient (CC) of feature values was unable to make a difference between features. Conclusions MI allowed to discriminate three features (M, SVR, and V) from the rest in a statistically significant manner. This result is consistent with the order obtained when sorting features by increasing values of extrema variability. MI is a promising alternative for selecting features to be considered as surrogate biomarkers in a precision medicine context.

  19. Temperature dependences of rate coefficients for electron catalyzed mutual neutralization

    NASA Astrophysics Data System (ADS)

    Shuman, Nicholas S.; Miller, Thomas M.; Friedman, Jeffrey F.; Viggiano, Albert A.; Maeda, Satoshi; Morokuma, Keiji

    2011-07-01

    The flowing afterglow technique of variable electron and neutral density attachment mass spectrometry (VENDAMS) has recently yielded evidence for a novel plasma charge loss process, electron catalyzed mutual neutralization (ECMN), i.e., A+ + B- + e- → A + B + e-. Here, rate constants for ECMN of two polyatomic species (POCl3- and POCl2-) and one diatomic species (Br2-) each with two monatomic cations (Ar+and Kr+) are measured using VENDAMS over the temperature range 300 K-500 K. All rate constants show a steep negative temperature dependence, consistent with that expected for a three body process involving two ions and an electron. No variation in rate constants as a function of the cation type is observed outside of uncertainty; however, rate constants of the polyatomic anions (˜1 × 10-18 cm6 s-1 at 300 K) are measurably higher than that for Br2- [(5.5 ± 2) × 10-19 cm6 s-1 at 300 K].

  20. Mutual optical intensity propagation through non-ideal mirrors.

    PubMed

    Meng, Xiangyu; Shi, Xianbo; Wang, Yong; Reininger, Ruben; Assoufid, Lahsen; Tai, Renzhong

    2017-09-01

    The mutual optical intensity (MOI) model is extended to include the propagation of partially coherent radiation through non-ideal mirrors. The propagation of the MOI from the incident to the exit plane of the mirror is realised by local ray tracing. The effects of figure errors can be expressed as phase shifts obtained by either the phase projection approach or the direct path length method. Using the MOI model, the effects of figure errors are studied for diffraction-limited cases using elliptical cylinder mirrors. Figure errors with low spatial frequencies can vary the intensity distribution, redistribute the local coherence function and distort the wavefront, but have no effect on the global degree of coherence. The MOI model is benchmarked against HYBRID and the multi-electron Synchrotron Radiation Workshop (SRW) code. The results show that the MOI model gives accurate results under different coherence conditions of the beam. Other than intensity profiles, the MOI model can also provide the wavefront and the local coherence function at any location along the beamline. The capability of tuning the trade-off between accuracy and efficiency makes the MOI model an ideal tool for beamline design and optimization.