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Sample records for micrornas show mutually

  1. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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)

  14. 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

  15. 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

  16. 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

  17. 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.…

  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. 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

    ... mutual), mutual marine insurance companies, mutual fire insurance companies issuing perpetual policies... Companies § 1.831-3 Tax on insurance companies (other than life or mutual), mutual marine insurance... insurance business within the United States, and all mutual marine insurance companies and mutual fire...

  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. 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

  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. 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.

  5. 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.

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. [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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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…

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  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. 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.

  17. 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

  18. 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.

  19. "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…

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. [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.

  13. 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...

  14. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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.

  17. 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.

  18. 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

    ... business within the United States, and all mutual marine insurance companies and mutual fire or flood insurance companies exclusively issuing perpetual policies or whose principal business is the issuance of...) Foreign insurance companies not carrying on an insurance business within the United States are not...

  19. 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

    ... insurance business within the United States, and all mutual marine insurance companies and mutual fire or flood insurance companies exclusively issuing perpetual policies or whose principal business is the...) Foreign insurance companies not carrying on an insurance business within the United States are not...

  20. 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...

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. [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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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

  2. 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.

  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. 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

  5. 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.

  6. 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

  7. 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

  8. [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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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…

  17. 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…

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  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. 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.

  13. 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.

  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. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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 Governing Facilities Used to Provide Commercial Mobile Radio Services § 90.165 Procedures for mutually exclusive applications. Mutually exclusive commercial mobile radio service applications are processed...

  3. 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.

  4. 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.

  5. 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

  6. 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

  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. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  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. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  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

    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.

  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 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

  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. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  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. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Degree of mutual ornamentation in birds is related to divorce rate.

    PubMed Central

    Kraaijeveld, Ken

    2003-01-01

    Many bird species have ornaments that are expressed equally in both sexes. I use comparative analysis to investigate why some monomorphic birds are highly ornamented, whereas others are drab. The results show a significant positive association between the degree of mutual ornamentation and divorce rate. This result is robust to the removal of the effects of phylogeny, site fidelity, residency, coloniality, nest type, mortality, body size and body-size dimorphism. The level of extra-pair paternity was not related to the degree of mutual ornamentation. I argue that these results are compatible with a process of mutual sexual selection, in which both sexes compete for access to mates. The coupled evolution of ornamentation and divorce rate, from the probable ancestral state of a high degree of ornamentation and a low divorce rate, appears to result mainly from a loss of ornamentation under mate fidelity. PMID:12964980

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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…

  18. 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...

  19. 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...

  20. 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...

  1. 47 CFR 22.131 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES PUBLIC MOBILE SERVICES Licensing Requirements and Procedures Applications and Notifications § 22... procedures in this section for processing mutually exclusive applications in the Public Mobile Services... 47 Telecommunication 2 2010-10-01 2010-10-01 false Procedures for mutually exclusive...

  2. 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…

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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

  4. 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…

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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).

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor.

    PubMed

    Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L; Lee, Chow H

    2017-03-03

    MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo, molecular beacons can also be employed to inhibit microRNAs in a specific manner.

  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. 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

  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. 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.

  11. 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.

  12. Modulation of microrna in two genetically disparate chicken lines showing different necrotic enteritis disease susceptibility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  14. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  15. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  16. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  17. Chemistry Game Shows

    NASA Astrophysics Data System (ADS)

    Campbell, Susan; Muzyka, Jennifer

    2002-04-01

    We present a technological improvement to the use of game shows to help students review for tests. Our approach uses HTML files interpreted with a browser on a computer attached to an LCD projector. The HTML files can be easily modified for use of the game in a variety of courses.

  18. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  19. Talk Show Science.

    ERIC Educational Resources Information Center

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  20. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  1. 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

  2. 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

  3. 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.

  4. NPK macronutrients and microRNA homeostasis.

    PubMed

    Kulcheski, Franceli R; Côrrea, Régis; Gomes, Igor A; de Lima, Júlio C; Margis, Rogerio

    2015-01-01

    Macronutrients are essential elements for plant growth and development. In natural, non-cultivated systems, the availability of macronutrients is not a limiting factor of growth, due to fast recycling mechanisms. However, their availability might be an issue in modern agricultural practices, since soil has been frequently over exploited. From a crop management perspective, the nitrogen (N), phosphorus (P), and potassium (K) are three important limiting factors and therefore frequently added as fertilizers. NPK are among the nutrients that have been reported to alter post-embryonic root developmental processes and consequently, impairs crop yield. To cope with nutrients scarcity, plants have evolved several mechanisms involved in metabolic, physiological, and developmental adaptations. In this scenario, microRNAs (miRNAs) have emerged as additional key regulators of nutrients uptake and assimilation. Some studies have demonstrated the intrinsic relation between miRNAs and their targets, and how they can modulate plants to deal with the NPK availability. In this review, we focus on miRNAs and their regulation of targets involved in NPK metabolism. In general, NPK starvation is related with miRNAs that are involved in root-architectural changes and uptake activity modulation. We further show that several miRNAs were discovered to be involved in plant-microbe symbiosis during N and P uptake, and in this way we present a global view of some studies that were conducted in the last years. The integration of current knowledge about miRNA-NPK signaling may help future studies to focus in good candidates genes for the development of important tools for plant nutritional breeding.

  5. NPK macronutrients and microRNA homeostasis

    PubMed Central

    Kulcheski, Franceli R.; Côrrea, Régis; Gomes, Igor A.; de Lima, Júlio C.; Margis, Rogerio

    2015-01-01

    Macronutrients are essential elements for plant growth and development. In natural, non-cultivated systems, the availability of macronutrients is not a limiting factor of growth, due to fast recycling mechanisms. However, their availability might be an issue in modern agricultural practices, since soil has been frequently over exploited. From a crop management perspective, the nitrogen (N), phosphorus (P), and potassium (K) are three important limiting factors and therefore frequently added as fertilizers. NPK are among the nutrients that have been reported to alter post-embryonic root developmental processes and consequently, impairs crop yield. To cope with nutrients scarcity, plants have evolved several mechanisms involved in metabolic, physiological, and developmental adaptations. In this scenario, microRNAs (miRNAs) have emerged as additional key regulators of nutrients uptake and assimilation. Some studies have demonstrated the intrinsic relation between miRNAs and their targets, and how they can modulate plants to deal with the NPK availability. In this review, we focus on miRNAs and their regulation of targets involved in NPK metabolism. In general, NPK starvation is related with miRNAs that are involved in root-architectural changes and uptake activity modulation. We further show that several miRNAs were discovered to be involved in plant–microbe symbiosis during N and P uptake, and in this way we present a global view of some studies that were conducted in the last years. The integration of current knowledge about miRNA-NPK signaling may help future studies to focus in good candidates genes for the development of important tools for plant nutritional breeding. PMID:26136763

  6. Identification of Dormancy-Associated MicroRNAs for the Design of Osteosarcoma-Targeted Dendritic Polyglycerol Nanopolyplexes.

    PubMed

    Tiram, Galia; Segal, Ehud; Krivitsky, Adva; Shreberk-Hassidim, Rony; Ferber, Shiran; Ofek, Paula; Udagawa, Taturo; Edry, Liat; Shomron, Noam; Roniger, Maayan; Kerem, Batsheva; Shaked, Yuval; Aviel-Ronen, Sarit; Barshack, Iris; Calderón, Marcelo; Haag, Rainer; Satchi-Fainaro, Ronit

    2016-02-23

    The presence of dormant, microscopic cancerous lesions poses a major obstacle for the treatment of metastatic and recurrent cancers. While it is well-established that microRNAs play a major role in tumorigenesis, their involvement in tumor dormancy has yet to be fully elucidated. We established and comprehensively characterized pairs of dormant and fast-growing human osteosarcoma models. Using these pairs of mouse tumor models, we identified three novel regulators of osteosarcoma dormancy: miR-34a, miR-93, and miR-200c. This report shows that loss of these microRNAs occurs during the switch from dormant avascular into fast-growing angiogenic phenotype. We validated their downregulation in patients' tumor samples compared to normal bone, making them attractive candidates for osteosarcoma therapy. Successful delivery of miRNAs is a challenge; hence, we synthesized an aminated polyglycerol dendritic nanocarrier, dPG-NH2, and designed dPG-NH2-microRNA polyplexes to target cancer. Reconstitution of these microRNAs using dPG-NH2 polyplexes into Saos-2 and MG-63 cells, which generate fast-growing osteosarcomas, reduced the levels of their target genes, MET proto-oncogene, hypoxia-inducible factor 1α, and moesin, critical to cancer angiogenesis and cancer cells' migration. We further demonstrate that these microRNAs attenuate the angiogenic capabilities of fast-growing osteosarcomas in vitro and in vivo. Treatment with each of these microRNAs using dPG-NH2 significantly prolonged the dormancy period of fast-growing osteosarcomas in vivo. Taken together, these findings suggest that nanocarrier-mediated delivery of microRNAs involved in osteosarcoma tumor-host interactions can induce a dormant-like state.

  7. The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction.

    PubMed

    Zou, Yan; Chiu, Hui; Domenger, Dorothée; Chuang, Chiou-Fen; Chang, Chieh

    2012-06-12

    miR-125 microRNAs, such as lin-4 in Caenorhabditis elegans, were among the first microRNAs discovered, are phylogenetically conserved, and have been implicated in regulating developmental timing. Here, we showed that loss-of-function mutations in lin-4 microRNA increased axon attraction mediated by the netrin homolog UNC-6. The absence of lin-4 microRNA suppressed the axon guidance defects of anterior ventral microtubule (AVM) neurons caused by loss-of-function mutations in slt-1, which encodes a repulsive guidance cue. Selective expression of lin-4 microRNA in AVM neurons of lin-4-null animals indicated that the effect of lin-4 on AVM axon guidance was cell-autonomous. Promoter reporter analysis suggested that lin-4 was likely expressed strongly in AVM neurons during the developmental time frame that the axons are guided to their targets. In contrast, the lin-4 reporter was barely detectable in anterior lateral microtubule (ALM) neurons, axon guidance of which is insensitive to netrin. In AVM neurons, the transcription factor LIN-14, a target of lin-4 microRNA, stimulated UNC-6-mediated ventral guidance of the AVM axon. LIN-14 promoted attraction of the AVM axon through the UNC-6 receptor UNC-40 [the worm homolog of vertebrate Deleted in Colorectal Cancer (DCC)] and its cofactor MADD-2, which signals through both the UNC-34 (Ena) and the CED-10 (Rac1) downstream pathways. LIN-14 stimulated UNC-6-mediated axon attraction in part by increasing UNC-40 abundance. Our study indicated that lin-4 microRNA reduced the activity of LIN-14 to terminate UNC-6-mediated axon guidance of AVM neurons.

  8. Differential MicroRNA Expression Profile in Myxomatous Mitral Valve Prolapse and Fibroelastic Deficiency Valves.

    PubMed

    Chen, Yei-Tsung; Wang, Juan; Wee, Abby S Y; Yong, Quek-Wei; Tay, Edgar Lik-Wui; Woo, Chin Cheng; Sorokin, Vitaly; Richards, Arthur Mark; Ling, Lieng-Hsi

    2016-05-18

    Myxomatous mitral valve prolapse (MMVP) and fibroelastic deficiency (FED) are two common variants of degenerative mitral valve disease (DMVD), which is a leading cause of mitral regurgitation worldwide. While pathohistological studies have revealed differences in extracellular matrix content in MMVP and FED, the molecular mechanisms underlying these two disease entities remain to be elucidated. By using surgically removed valvular specimens from MMVP and FED patients that were categorized on the basis of echocardiographic, clinical and operative findings, a cluster of microRNAs that expressed differentially were identified. The expressions of has-miR-500, -3174, -17, -1193, -646, -1273e, -4298, -203, -505, and -939 showed significant differences between MMVP and FED after applying Bonferroni correction (p < 0.002174). The possible involvement of microRNAs in the pathogenesis of DMVD were further suggested by the presences of in silico predicted target sites on a number of genes reported to be involved in extracellular matrix homeostasis and marker genes for cellular composition of mitral valves, including decorin (DCN), aggrecan (ACAN), fibromodulin (FMOD), α actin 2 (ACTA2), extracellular matrix protein 2 (ECM2), desmin (DES), endothelial cell specific molecule 1 (ESM1), and platelet/ endothelial cell adhesion molecule 1 (PECAM1), as well as inverse correlations of selected microRNA and mRNA expression in MMVP and FED groups. Our results provide evidence that distinct molecular mechanisms underlie MMVP and FED. Moreover, the microRNAs identified may be targets for the future development of diagnostic biomarkers and therapeutics.

  9. High-Salt Intake Suppressed MicroRNA-133a Expression in Dahl SS Rat Myocardium

    PubMed Central

    Guo, Tong-Shuai; Zhang, Jie; Mu, Jian-Jun; Liu, Fu-Qiang; Yuan, Zu-Yi; Ren, Ke-Yu; Wang, Dan

    2014-01-01

    Salt-sensitive individuals show earlier and more serious cardiac damage than nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to investigate the different functions of high-salt intake on salt-sensitive (SS) rats and Sprague-Dawley (SD) rats and the involvement of microRNA-133a in these roles. After high-salt intervention, the left ventricular mass (LVW) and left ventricular mass index (LVMI) of the salt-sensitive high salt (SHS) group were obviously higher than those of the salt-sensitive low salt (SLS) group. However, the difference between the Sprague-Dawley high salt (DHS) group and the Sprague-Dawley low salt (DLS) group was not significant. Compared with SLS group, collagen I and connective tissue growth factor (CTGF) in the heart of SHS group were significantly higher, whereas no statistical difference was observed between the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in the heart of both strains were significantly decreased, but that in the SHS group decreased more significantly. These results suggest that high salt intervention could down-regulate the expression of myocardial microRNA-133a, which may be one of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension. PMID:24937684

  10. An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans

    PubMed Central

    Kato, Masaomi; Kashem, Mohammed Abul; Cheng, Chao

    2016-01-01

    Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic – a mild and long-term – oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. PMID:27623524

  11. Differential MicroRNA Expression Profile in Myxomatous Mitral Valve Prolapse and Fibroelastic Deficiency Valves

    PubMed Central

    Chen, Yei-Tsung; Wang, Juan; Wee, Abby S. Y.; Yong, Quek-Wei; Tay, Edgar Lik-Wui; Woo, Chin Cheng; Sorokin, Vitaly; Richards, Arthur Mark; Ling, Lieng-Hsi

    2016-01-01

    Myxomatous mitral valve prolapse (MMVP) and fibroelastic deficiency (FED) are two common variants of degenerative mitral valve disease (DMVD), which is a leading cause of mitral regurgitation worldwide. While pathohistological studies have revealed differences in extracellular matrix content in MMVP and FED, the molecular mechanisms underlying these two disease entities remain to be elucidated. By using surgically removed valvular specimens from MMVP and FED patients that were categorized on the basis of echocardiographic, clinical and operative findings, a cluster of microRNAs that expressed differentially were identified. The expressions of has-miR-500, -3174, -17, -1193, -646, -1273e, -4298, -203, -505, and -939 showed significant differences between MMVP and FED after applying Bonferroni correction (p < 0.002174). The possible involvement of microRNAs in the pathogenesis of DMVD were further suggested by the presences of in silico predicted target sites on a number of genes reported to be involved in extracellular matrix homeostasis and marker genes for cellular composition of mitral valves, including decorin (DCN), aggrecan (ACAN), fibromodulin (FMOD), α actin 2 (ACTA2), extracellular matrix protein 2 (ECM2), desmin (DES), endothelial cell specific molecule 1 (ESM1), and platelet/ endothelial cell adhesion molecule 1 (PECAM1), as well as inverse correlations of selected microRNA and mRNA expression in MMVP and FED groups. Our results provide evidence that distinct molecular mechanisms underlie MMVP and FED. Moreover, the microRNAs identified may be targets for the future development of diagnostic biomarkers and therapeutics. PMID:27213335

  12. Expression analysis of multiple microRNAs in each patient with scleroderma.

    PubMed

    Koba, Shigeru; Jinnin, Masatoshi; Inoue, Kuniko; Nakayama, Wakana; Honda, Noritoshi; Makino, Katsunari; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Ihn, Hironobu

    2013-07-01

    In this study, we compared expression pattern of multiple microRNAs in individual patient with scleroderma with that in normal subject. Serum levels of six microRNAs (miR-7 g, miR-21, miR-29b, miR-125, miR-145 and miR-206) were evaluated using real-time PCR in 15 patients with scleroderma and 15 normal subjects. While levels of the six microRNAs were similar between the two groups, we found significant difference in the ranks between miRNAs in patients with scleroderma. Additionally, levels of let-7 g and miR-125b showed strong and significant correlation in normal subjects, but not in patients with scleroderma. Thus, miRNA expression pattern may be different in patients with scleroderma. We also found the combination of serum levels of miR-206 and miR-21 was more useful in distinguishing patients with scleroderma from normal subjects than either miR-206 or miR-21 alone. Our study is the first to demonstrate different expression profiles of multiple microRNAs in each patient with scleroderma and examine its clinical significance.

  13. Link Prediction in Weighted Networks: A Weighted Mutual Information Model

    PubMed Central

    Zhu, Boyao; Xia, Yongxiang

    2016-01-01

    The link-prediction problem is an open issue in data mining and knowledge discovery, which attracts researchers from disparate scientific communities. A wealth of methods have been proposed to deal with this problem. Among these approaches, most are applied in unweighted networks, with only a few taking the weights of links into consideration. In this paper, we present a weighted model for undirected and weighted networks based on the mutual information of local network structures, where link weights are applied to further enhance the distinguishable extent of candidate links. Empirical experiments are conducted on four weighted networks, and results show that the proposed method can provide more accurate predictions than not only traditional unweighted indices but also typical weighted indices. Furthermore, some in-depth discussions on the effects of weak ties in link prediction as well as the potential to predict link weights are also given. This work may shed light on the design of algorithms for link prediction in weighted networks. PMID:26849659

  14. A new mutually reinforcing network node and link ranking algorithm

    NASA Astrophysics Data System (ADS)

    Wang, Zhenghua; Dueñas-Osorio, Leonardo; Padgett, Jamie E.

    2015-10-01

    This study proposes a novel Normalized Wide network Ranking algorithm (NWRank) that has the advantage of ranking nodes and links of a network simultaneously. This algorithm combines the mutual reinforcement feature of Hypertext Induced Topic Selection (HITS) and the weight normalization feature of PageRank. Relative weights are assigned to links based on the degree of the adjacent neighbors and the Betweenness Centrality instead of assigning the same weight to every link as assumed in PageRank. Numerical experiment results show that NWRank performs consistently better than HITS, PageRank, eigenvector centrality, and edge betweenness from the perspective of network connectivity and approximate network flow, which is also supported by comparisons with the expensive N-1 benchmark removal criteria based on network efficiency. Furthermore, it can avoid some problems, such as the Tightly Knit Community effect, which exists in HITS. NWRank provides a new inexpensive way to rank nodes and links of a network, which has practical applications, particularly to prioritize resource allocation for upgrade of hierarchical and distributed networks, as well as to support decision making in the design of networks, where node and link importance depend on a balance of local and global integrity.

  15. Mutualism or parasitism? The variable outcome of cleaning symbioses

    PubMed Central

    Cheney, Karen L; Côté, Isabelle M

    2005-01-01

    The exact nature of many interspecific interactions remains unclear, with some evidence suggesting mutualism and other evidence pointing to parasitism for the same pair of interacting species. Here, we show spatial variation in the outcome of the cleaning relationship between Caribbean cleaning gobies (Elacatinus evelynae) and longfin damselfish (Stegastes diencaeus) over the distribution range of these species, and link this variation to the availability of ectoparasites. Cleaning interactions at sites with more ectoparasites were characterized by greater reductions in ectoparasite loads on damselfish clients and lower rates of removal of scales and mucus (i.e. cheating) by cleaning gobies, whereas the opposite was observed at sites where ectoparasite abundance was lower. For damselfish clients, cleaning was therefore clearly mutualistic in some locations, but sometimes neutral or even parasitic in others. Seasonal variability in ectoparasite abundance may ensure that locally low parasite availability, which promotes cleanerfish cheating, may be a transient condition at any given site. Conflicting conclusions about the nature of cleaning symbioses may, therefore, be explained by variation in ectoparasite abundance. PMID:17148155

  16. Finding Mutual Exclusion Invariants in Temporal Planning Domains

    NASA Technical Reports Server (NTRS)

    Bernardini, Sara; Smith, David E.

    2011-01-01

    We present a technique for automatically extracting temporal mutual exclusion invariants from PDDL2.2 planning instances. We first identify a set of invariant candidates by inspecting the domain and then check these candidates against properties that assure invariance. If these properties are violated, we show that it is sometimes possible to refine a candidate by adding additional propositions and turn it into a real invariant. Our technique builds on other approaches to invariant synthesis presented in the literature, but departs from their limited focus on instantaneous discrete actions by addressing temporal and numeric domains. To deal with time, we formulate invariance conditions that account for both the entire structure of the operators (including the conditions, rather than just the effects) and the possible interactions between operators. As a result, we construct a technique that is not only capable of identifying invariants for temporal domains, but is also able to find a broader set of invariants for non-temporal domains than the previous techniques.

  17. 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.

  18. 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].

  19. 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.

  20. A new mutually reinforcing network node and link ranking algorithm

    PubMed Central

    Wang, Zhenghua; Dueñas-Osorio, Leonardo; Padgett, Jamie E.

    2015-01-01

    This study proposes a novel Normalized Wide network Ranking algorithm (NWRank) that has the advantage of ranking nodes and links of a network simultaneously. This algorithm combines the mutual reinforcement feature of Hypertext Induced Topic Selection (HITS) and the weight normalization feature of PageRank. Relative weights are assigned to links based on the degree of the adjacent neighbors and the Betweenness Centrality instead of assigning the same weight to every link as assumed in PageRank. Numerical experiment results show that NWRank performs consistently better than HITS, PageRank, eigenvector centrality, and edge betweenness from the perspective of network connectivity and approximate network flow, which is also supported by comparisons with the expensive N-1 benchmark removal criteria based on network efficiency. Furthermore, it can avoid some problems, such as the Tightly Knit Community effect, which exists in HITS. NWRank provides a new inexpensive way to rank nodes and links of a network, which has practical applications, particularly to prioritize resource allocation for upgrade of hierarchical and distributed networks, as well as to support decision making in the design of networks, where node and link importance depend on a balance of local and global integrity. PMID:26492958

  1. Mutual synchronization between structure and central pattern generator

    NASA Astrophysics Data System (ADS)

    Hongu, Junichi; Iba, Daisuke

    2012-04-01

    This paper shows an evaluating method of synchronization between a structure and Central Pattern Generators (CPGs), which are embedded in a controller designed for an active mass damper. A neural oscillator composing the CPGs has nonlinear and entrainment properties. Therefore, the proposed controller has possibility to exhibit the characteristic of robustness, when the structural parameters, i.e. stiffness or damping, are changed by earthquakes and the like. Our earlier studies have proposed the new controller and ascertained the efficacy of vibration suppression. However, there has been no study to evaluate the controller's above-mentioned properties. For tuning into practical application, the reliability and robustness along with the controller's vibration mitigation performance must be analyzed. In this paper, phase reduction theory is tried to appraise the synchronization between a structure and the CPGs. In this case, the synchronization between the target structure and a single neural oscillator constituting the CPGs is required to be investigated. Therefore, the single neural oscillator's the harmonization characteristic with sinusoidal input is firstly examined, and the synchronization region is expressed using phase response curves. In addition, the mutual synchronization between the structure and the single neural oscillator is studied under sinusoidal input using the result of the harmonization characteristic.

  2. 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].

  3. 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.

  4. Fast registration algorithm using a variational principle for mutual information

    NASA Astrophysics Data System (ADS)

    Alexander, Murray E.; Summers, Randy

    2003-05-01

    A method is proposed for cross-modal image registration based on mutual information (MI) matching criteria. Both conventional and "normalized" MI are considered. MI may be expressed as a functional of a general image displacement field u. The variational principle for MI provides a field equation for u. The method employs a set of "registration points" consisting of a prescribed number of strongest edge points of the reference image, and minimizes an objective function D defined as the sum of the square residuals of the field equation for u at these points, where u is expressed as a sum over a set of basis functions (the affine model is presented here). D has a global minimum when the images are aligned, with a "basin of attraction" typically of width ~0.3 pixels. By pre-filtering with a low-pass filter, and using a multiresolution image pyramid, the basin may be significantly widened. The Levenberg-Marquardt algorithm is used to minimize D. Tests using randomly distributed misalignments of image pairs show that registration accuracy of 0.02 - 0.07 pixels is achieved, when using cubic B-splines for image representation, interpolation, and Parzen window estimation.

  5. A reliable RFID mutual authentication scheme for healthcare environments.

    PubMed

    Wu, Zhen-Yu; Chen, Lichin; Wu, Ju-Chuan

    2013-04-01

    Radio frequency identification (RFID) applications have the potential to increase the reliability of healthcare environments. However, there are obvious security and privacy concerns with regard to storing personal and medical data in RFID tags, and the lack of secure authentication systems in healthcare environments remains as a challenge the further use of this technology, one that touches on issues of confidentiality, unforgeability, location privacy, and scalability. This study proposes a novel mutual authentication protocol that considers all of these issues and solves the tradeoff between location privacy and scalability in healthcare environments. A formal proof and analysis is demonstrated to prove the effectiveness of the proposed scheme, and that high reliability has and can be easily deployed and managed. This study also provides a scenario example that applied proposed protocol in the newborn care and management. The result shows that the proposed scheme solves the related tradeoff problem, and is capable of providing both location privacy and scalability. To apply the authentication scheme proposed in this work would be able to increase confidence in future implementations of RFID systems in healthcare environments.

  6. Mutually unbiased bases as minimal Clifford covariant 2-designs

    NASA Astrophysics Data System (ADS)

    Zhu, Huangjun

    2015-06-01

    Mutually unbiased bases (MUBs) are interesting for various reasons. The most attractive example of (a complete set of) MUBs is the one constructed by Ivanović as well as Wootters and Fields, which is referred to as the canonical MUB. Nevertheless, little is known about anything that is unique to this MUB. We show that the canonical MUB in any prime power dimension is uniquely determined by an extremal orbit of the (restricted) Clifford group except in dimension 3, in which case the orbit defines a special symmetric informationally complete measurement (SIC), known as the Hesse SIC. Here the extremal orbit is the orbit with the smallest number of pure states. Quite surprisingly, this characterization does not rely on any concept that is related to bases or unbiasedness. As a corollary, the canonical MUB is the unique minimal 2-design covariant with respect to the Clifford group except in dimension 3. In addition, these MUBs provide an infinite family of highly symmetric frames and positive-operator-valued measures (POVMs), which are of independent interest.

  7. microRNA-140 Inhibits Inflammation and Stimulates Chondrogenesis in a Model of Interleukin 1β-induced Osteoarthritis

    PubMed Central

    Karlsen, Tommy A; de Souza, Gustavo Antonio; Ødegaard, Bjørn; Engebretsen, Lars; Brinchmann, Jan E

    2016-01-01

    Osteoarthritis is a serious disease of articular cartilage. The pathogenic factors contributing to this disorder are inflammation, extracellular matrix degradation and failure to rebuild the articular cartilage. Preclinical studies suggest that microRNA-140 may play a protective role in osteoarthritis development, but little is known about the mechanism by which this occurs. Here we present the results of forced expression of microRNA-140 in an in vitro model of osteoarthritis, evaluated by global proteomics analysis. We show that inflammation was reduced through the altered levels of multiple proteins involved in the nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 pathway. microRNA-140 upregulated many of the components involved in the synthesis of hyaline extracellular matrix and reduced the levels of aggrecanases and syndecan 4, thus potentially both increasing cartilage repair and reducing cartilage breakdown. These results show how forced expression of microRNA-140 is likely to counteract all three pathogenic processes, and support the idea that intra-articular injection of microRNA-140 may benefit patients suffering from early osteoarthritis. PMID:27727249

  8. MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer.

    PubMed

    Torruella-Loran, Ignasi; Laayouni, Hafid; Dobon, Begoña; Gallego, Alicia; Balcells, Ingrid; Garcia-Ramallo, Eva; Espinosa-Parrilla, Yolanda

    2016-10-01

    Nucleotide variants in microRNA regions have been associated with disease; nevertheless, few studies still have addressed the allele-dependent effect of these changes. We studied microRNA genetic variation in human populations and found that while low-frequency variants accumulate indistinctly in microRNA regions, the mature and seed regions tend to be depleted of high-frequency variants, probably as a result of purifying selection. Comparison of pairwise population fixation indexes among regions showed that the seed had higher population fixation indexes than the other regions, suggesting the existence of local adaptation in the seed region. We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B). We found differences in the expression between alleles and in the regulation of several genes involved in cancer, such as TP53, KIT, CDH1, CLH, and TERT, which may result in changes in regulatory networks related to tumorigenesis. Furthermore, luciferase-based assays showed that MIR499A could be regulating the cadherin CDH1 and the cell adhesion molecule CLH1 in an allele-dependent fashion. A better understanding of the effect of microRNA variants associated with disease could be key in our way to a more personalized medicine.

  9. TP53/MicroRNA Interplay in Hepatocellular Carcinoma

    PubMed Central

    Pollutri, Daniela; Gramantieri, Laura; Bolondi, Luigi; Fornari, Francesca

    2016-01-01

    The role of microRNAs as oncogenes and tumor suppressor genes has emerged in several cancers, including hepatocellular carcinoma (HCC). The pivotal tumor suppressive role of p53-axis is indicated by the presence of inactivating mutations in TP53 gene in nearly all cancers. A close interaction between these two players, as well as the establishment of complex p53/miRNAs loops demonstrated the strong contribution of p53-effector miRNAs in enhancing the p53-mediated tumor suppression program. On the other hand, the direct and indirect targeting of p53, as well as the regulation of its stability and activity by specific microRNAs, underlie the importance of the fine-tuning of p53 pathway, affecting the cell fate of damaged/transformed cells. The promising results of miRNAs-based therapeutic approaches in preclinical studies and their entrance in clinical trials demonstrate the feasibility of this strategy in several diseases, including cancer. Molecularly targeted drugs approved so far for HCC treatment show intrinsic or acquired resistances with disease progression in many cases, therefore the identification of effective and non-toxic agents for the treatment of HCC is actually an unmet clinical need. The knowledge of p53/miRNA inter-relations in HCC may provide useful elements for the identification of novel combined approaches in the context of the “personalized-medicine” era. PMID:27918441

  10. MicroRNA 329 Suppresses Angiogenesis by Targeting CD146

    PubMed Central

    Wang, Ping; Luo, Yongting; Duan, Hongxia; Xing, Shu; Zhang, Jianlin; Lu, Di; Feng, Jing; Yang, Dongling; Song, Lina

    2013-01-01

    CD146, an endothelial biomarker, has been shown to be aberrantly upregulated during pathological angiogenesis and functions as a coreceptor for vascular endothelial growth factor receptor 2 (VEGFR-2) to promote disease progression. However, the regulatory mechanisms of CD146 expression during angiogenesis remain unclear. Using a microRNA screening approach, we identified a novel negative regulator of angiogenesis, microRNA 329 (miR-329), that directly targeted CD146 and inhibited CD146-mediated angiogenesis in vitro and in vivo. Endogenous miR-329 expression was downregulated by VEGF and tumor necrosis factor alpha (TNF-α), resulting in the elevation of CD146 in endothelial cells. Upregulation of CD146 facilitated an endothelial response to VEGF-induced SRC kinase family (SKF)/p38 mitogen-activated protein kinase (MAPK)/NF-κB activation and consequently promoted endothelial cell migration and tube formation. Our animal experiments showed that treatment with miR-329 repressed excessive CD146 expression on blood vessels and significantly attenuated neovascularization in a mouse model of pathological angiogenesis. Our findings provide the first evidence that CD146 expression in angiogenesis is regulated by miR-329 and suggest that miR-329 could present a potential therapeutic tool for the treatment of angiogenic diseases. PMID:23878390

  11. TMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways.

    PubMed

    Chen-Plotkin, Alice S; Unger, Travis L; Gallagher, Michael D; Bill, Emily; Kwong, Linda K; Volpicelli-Daley, Laura; Busch, Johanna I; Akle, Sebastian; Grossman, Murray; Van Deerlin, Vivianna; Trojanowski, John Q; Lee, Virginia M-Y

    2012-08-15

    Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a fatal neurodegenerative disease with no available treatments. Mutations in the progranulin gene (GRN) causing impaired production or secretion of progranulin are a common Mendelian cause of FTLD-TDP; additionally, common variants at chromosome 7p21 in the uncharacterized gene TMEM106B were recently linked by genome-wide association to FTLD-TDP with and without GRN mutations. Here we show that TMEM106B is neuronally expressed in postmortem human brain tissue, and that expression levels are increased in FTLD-TDP brain. Furthermore, using an unbiased, microarray-based screen of >800 microRNAs (miRs), we identify microRNA-132 as the top microRNA differentiating FTLD-TDP and control brains, with <50% normal expression levels of three members of the microRNA-132 cluster (microRNA-132, microRNA-132*, and microRNA-212) in disease. Computational analyses, corroborated empirically, demonstrate that the top mRNA target of both microRNA-132 and microRNA-212 is TMEM106B; both microRNAs repress TMEM106B expression through shared microRNA-132/212 binding sites in the TMEM106B 3'UTR. Increasing TMEM106B expression to model disease results in enlargement and poor acidification of endo-lysosomes, as well as impairment of mannose-6-phosphate-receptor trafficking. Finally, endogenous neuronal TMEM106B colocalizes with progranulin in late endo-lysosomes, and TMEM106B overexpression increases intracellular levels of progranulin. Thus, TMEM106B is an FTLD-TDP risk gene, with microRNA-132/212 depression as an event which can lead to aberrant overexpression of TMEM106B, which in turn alters progranulin pathways. Evidence for this pathogenic cascade includes the striking convergence of two independent, genomic-scale screens on a microRNA:mRNA regulatory pair. Our findings open novel directions for elucidating miR-based therapies in FTLD-TDP.

  12. Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer

    PubMed Central

    Azizian, Azadeh; Epping, Ingo; Kramer, Frank; Jo, Peter; Bernhardt, Markus; Kitz, Julia; Salinas, Gabriela; Wolff, Hendrik A.; Grade, Marian; Beißbarth, Tim; Ghadimi, B. Michael; Gaedcke, Jochen

    2016-01-01

    Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs. Results: In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p < 0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage. Conclusion: Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients’ therapy if validated in a prospective study. PMID:27092493

  13. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show.

  14. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre.

  15. MicroRNAs to Pathways in Prostate Cancer Progression

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-12-1-0474 TITLE: “ MICRORNAS TO PATHWAYS IN PROSTATE CANCER...2013 – 29 th Sept,2014 4. TITLE AND SUBTITLE MicroRNAs to Pathways in Prostate Cancer Progression 5a. CONTRACT NUMBER - 5b. GRANT NUMBER W81XWH...the proposal focuses on a class of non-coding RNAs called microRNAs that function to suppress large networks of genes during cell fate transitions

  16. A general framework for effectiveness concepts in mutualisms.

    PubMed

    Schupp, Eugene W; Jordano, Pedro; Gómez, José María

    2017-03-28

    A core interest in studies of mutualistic interactions is the 'effectiveness' of mutualists in providing benefits to their partners. In plant-animal mutualisms it is widely accepted that the total effect of a mutualist on its partner is estimated as (1) a 'quantity' component multiplied by (2) a 'quality' component, although the meanings of 'effectiveness,' 'quantity,' and 'quality' and which terms are applied to these metrics vary greatly across studies. In addition, a similar quantity × quality = total effect approach has not been applied to other types of mutualisms, although it could be informative. Lastly, when a total effect approach has been applied, it has invariably been from a phytocentric perspective, focussing on the effects of animal mutualists on their plant partner. This lack of a common framework of 'effectiveness' of mutualistic interactions limits generalisation and the development of a broader understanding of the ecology and evolution of mutualisms. In this paper, we propose a general framework and demonstrate its utility by applying it to both partners in five different types of mutualisms: pollination, seed dispersal, plant protection, rhizobial, and mycorrhizal mutualisms. We then briefly discuss the flexibility of the framework, potential limitations, and relationship to other approaches.

  17. Persistence of pollination mutualisms in the presence of ants.

    PubMed

    Wang, Yuanshi; Wang, Shikun

    2015-01-01

    This paper considers plant-pollinator-ant systems in which the plant-pollinator interaction is mutualistic but ants have both positive and negative effects on plants. The ants also interfere with pollinators by preventing them from accessing plants. While a Beddington-DeAngelis (BD) formula can describe the plant-pollinator interaction, the formula is extended in this paper to characterize the pollination mutualism under the ant interference. Then, a plant-pollinator-ant system with the extended BD functional response is discussed, and global dynamics of the model demonstrate the mechanisms by which pollination mutualism can persist in the presence of ants. When the ant interference is strong, it can result in extinction of pollinators. Moreover, if the ants depend on pollination mutualism for survival, the strong interference could drive pollinators into extinction, which consequently lead to extinction of the ants themselves. When the ant interference is weak, a cooperation between plant-ant and plant-pollinator mutualisms could occur, which promotes survival of both ants and pollinators, especially in the case that ants (respectively, pollinators) cannot survive in the absence of pollinators (respectively, ants). Even when the level of ant interference remains invariant, varying ants' negative effect on plants can result in survival/extinction of both ants and pollinators. Therefore, our results provide an explanation for the persistence of pollination mutualism when there exist ants.

  18. Mutualism Disruption Threatens Global Plant Biodiversity: A Systematic Review

    PubMed Central

    Aslan, Clare E.; Zavaleta, Erika S.; Tershy, Bernie; Croll, Donald

    2013-01-01

    Background As global environmental change accelerates, biodiversity losses can disrupt interspecific interactions. Extinctions of mutualist partners can create “widow” species, which may face reduced ecological fitness. Hypothetically, such mutualism disruptions could have cascading effects on biodiversity by causing additional species coextinctions. However, the scope of this problem – the magnitude of biodiversity that may lose mutualist partners and the consequences of these losses – remains unknown. Methodology/Principal Findings We conducted a systematic review and synthesis of data from a broad range of sources to estimate the threat posed by vertebrate extinctions to the global biodiversity of vertebrate-dispersed and -pollinated plants. Though enormous research gaps persist, our analysis identified Africa, Asia, the Caribbean, and global oceanic islands as geographic regions at particular risk of disruption of these mutualisms; within these regions, percentages of plant species likely affected range from 2.1–4.5%. Widowed plants are likely to experience reproductive declines of 40–58%, potentially threatening their persistence in the context of other global change stresses. Conclusions Our systematic approach demonstrates that thousands of species may be impacted by disruption in one class of mutualisms, but extinctions will likely disrupt other mutualisms, as well. Although uncertainty is high, there is evidence that mutualism disruption directly threatens significant biodiversity in some geographic regions. Conservation measures with explicit focus on mutualistic functions could be necessary to bolster populations of widowed species and maintain ecosystem functions. PMID:23840571

  19. Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets.

    PubMed

    Bossel Ben-Moshe, Noa; Avraham, Roi; Kedmi, Merav; Zeisel, Amit; Yitzhaky, Assif; Yarden, Yosef; Domany, Eytan

    2012-11-01

    MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miR's targets is a considerable bioinformatic challenge of great importance for inferring the miR's function. Sequence-based prediction algorithms have high false-positive rates, are not in agreement, and are not biological context specific. Here we introduce CoSMic (Context-Specific MicroRNA analysis), an algorithm that combines sequence-based prediction with miR and mRNA expression data. CoSMic differs from existing methods--it identifies miRs that play active roles in the specific biological system of interest and predicts with less false positives their functional targets. We applied CoSMic to search for miRs that regulate the migratory response of human mammary cells to epidermal growth factor (EGF) stimulation. Several such miRs, whose putative targets were significantly enriched by migration processes were identified. We tested three of these miRs experimentally, and showed that they indeed affected the migratory phenotype; we also tested three negative controls. In comparison to other algorithms CoSMic indeed filters out false positives and allows improved identification of context-specific targets. CoSMic can greatly facilitate miR research in general and, in particular, advance our understanding of individual miRs' function in a specific context.

  20. Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets

    PubMed Central

    Bossel Ben-Moshe, Noa; Avraham, Roi; Kedmi, Merav; Zeisel, Amit; Yitzhaky, Assif; Yarden, Yosef; Domany, Eytan

    2012-01-01

    MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miR’s targets is a considerable bioinformatic challenge of great importance for inferring the miR’s function. Sequence-based prediction algorithms have high false-positive rates, are not in agreement, and are not biological context specific. Here we introduce CoSMic (Context-Specific MicroRNA analysis), an algorithm that combines sequence-based prediction with miR and mRNA expression data. CoSMic differs from existing methods—it identifies miRs that play active roles in the specific biological system of interest and predicts with less false positives their functional targets. We applied CoSMic to search for miRs that regulate the migratory response of human mammary cells to epidermal growth factor (EGF) stimulation. Several such miRs, whose putative targets were significantly enriched by migration processes were identified. We tested three of these miRs experimentally, and showed that they indeed affected the migratory phenotype; we also tested three negative controls. In comparison to other algorithms CoSMic indeed filters out false positives and allows improved identification of context-specific targets. CoSMic can greatly facilitate miR research in general and, in particular, advance our understanding of individual miRs’ function in a specific context. PMID:22977182

  1. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave

  2. A MicroRNA Precursor Surveillance System in Quality Control of MicroRNA Synthesis

    PubMed Central

    Liu, Xuhang; Zheng, Qi; Vrettos, Nicholas; Maragkakis, Manolis; Alexiou, Panagiotis; Gregory, Brian D.; Mourelatos, Zissimos

    2014-01-01

    Summary MicroRNAs (miRNAs) are essential for regulation of gene expression. Though numerous miRNAs have been identified by high throughput sequencing, few precursor miRNAs (pre-miRNAs) are experimentally validated. Here we report a strategy for constructing high-throughput sequencing libraries enriched for full-length pre-miRNAs. We find widespread and extensive uridylation of Argonaute bound pre-miRNAs, which is primarily catalyzed by two terminal uridylyltransferases: TUT7 and TUT4. Uridylation by TUT7/4 not only polishes pre-miRNA 3′ ends, but also facilitates their degradation by the exosome, preventing clogging of Ago with defective species. We show that the exosome exploits distinct substrate preferences of DIS3 and RRP6, its two catalytic subunits, to distinguish productive from defective pre-miRNAs. Furthermore, we identify a positive feedback loop formed by the exosome and TUT7/4 in triggering uridylation and degradation of Ago-bound pre-miRNAs. Our study reveals a pre-miRNA surveillance system that comprises TUT7, TUT4 and the exosome in quality control of miRNA synthesis. PMID:25175028

  3. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  4. 12 CFR Appendix A to Part 239 - Mutual Holding Company Model Charter

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Mutual Holding Company Model Charter A Appendix... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Pt. 239, App. A Appendix A to Part 239—Mutual Holding Company Model Charter FEDERAL MUTUAL HOLDING COMPANY CHARTER Section 1: Corporate...

  5. 12 CFR >appendix A to Part 239 - Mutual Holding Company Model Charter

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Mutual Holding Company Model Charter A... FEDERAL RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Pt. 239, App. A >Appendix A to Part 239—Mutual Holding Company Model Charter FEDERAL MUTUAL HOLDING COMPANY CHARTER Section...

  6. 12 CFR Appendix C to Part 239 - Mutual Holding Company Model Bylaws

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Mutual Holding Company Model Bylaws C Appendix... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Pt. 239, App. C Appendix C to Part 239—Mutual Holding Company Model Bylaws MODEL BYLAWS FOR MUTUAL HOLDING COMPANIES The term “trustees” may...

  7. 12 CFR Appendix A to Part 239 - Mutual Holding Company Model Charter

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Mutual Holding Company Model Charter A Appendix... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Pt. 239, App. A Appendix A to Part 239—Mutual Holding Company Model Charter FEDERAL MUTUAL HOLDING COMPANY CHARTER Section 1: Corporate...

  8. 12 CFR Appendix C to Part 239 - Mutual Holding Company Model Bylaws

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Mutual Holding Company Model Bylaws C Appendix... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Pt. 239, App. C Appendix C to Part 239—Mutual Holding Company Model Bylaws MODEL BYLAWS FOR MUTUAL HOLDING COMPANIES The term “trustees” may...

  9. 12 CFR Appendix C to Part 239 - Mutual Holding Company Model Bylaws

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Mutual Holding Company Model Bylaws C Appendix... RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Pt. 239, App. C Appendix C to Part 239—Mutual Holding Company Model Bylaws MODEL BYLAWS FOR MUTUAL HOLDING COMPANIES The term “trustees” may...

  10. MicroRNAs: Emerging Novel Clinical Biomarkers for Hepatocellular Carcinomas

    PubMed Central

    Anwar, Sumadi Lukman; Lehmann, Ulrich

    2015-01-01

    The discovery of small non-coding RNAs known as microRNAs has refined our view of the complexity of gene expression regulation. In hepatocellular carcinoma (HCC), the fifth most frequent cancer and the third leading cause of cancer death worldwide, dysregulation of microRNAs has been implicated in all aspects of hepatocarcinogenesis. In addition, alterations of microRNA expression have also been reported in non-cancerous liver diseases including chronic hepatitis and liver cirrhosis. MicroRNAs have been proposed as clinically useful diagnostic biomarkers to differentiate HCC from different liver pathologies and healthy controls. Unique patterns of microRNA expression have also been implicated as biomarkers for prognosis as well as to predict and monitor therapeutic responses in HCC. Since dysregulation has been detected in various specimens including primary liver cancer tissues, serum, plasma, and urine, microRNAs represent novel non-invasive markers for HCC screening and predicting therapeutic responses. However, despite a significant number of studies, a consensus on which microRNA panels, sample types, and methodologies for microRNA expression analysis have to be used has not yet been established. This review focuses on potential values, benefits, and limitations of microRNAs as new clinical markers for diagnosis, prognosis, prediction, and therapeutic monitoring in HCC. PMID:26295264

  11. Role of micro-RNA in colorectal cancer screening.

    PubMed

    Rodríguez-Montes, José Antonio; Menéndez Sánchez, Pablo

    2014-12-01

    MicroRNAs are involved in carcinogenesis through postranscriptional gene regulatory activity. These molecules are involved in various physiological and pathological functions, such as apoptosis, cell proliferation and differentiation, which indicates their functionality in carcinogenesis as tumour suppressor genes or oncogenes. Several studies have determined the presence of microRNAs in different neoplastic diseases such as colon, prostate, breast, stomach, pancreas, and lung cancer. There are promising data on the usefulness of quantifying microRNAs in different organic fluids and tissues. We have conducted a review of the determinations of microRNAs in the diagnosis of colorectal cancer.

  12. Sequence Fingerprints of MicroRNA Conservation

    PubMed Central

    Shi, Bing; Gao, Wei; Wang, Juan

    2012-01-01

    It is known that the conservation of protein-coding genes is associated with their sequences both various species, such as animals and plants. However, the association between microRNA (miRNA) conservation and their sequences in various species remains unexplored. Here we report the association of miRNA conservation with its sequence features, such as base content and cleavage sites, suggesting that miRNA sequences contain the fingerprints for miRNA conservation. More interestingly, different species show different and even opposite patterns between miRNA conservation and sequence features. For example, mammalian miRNAs show a positive/negative correlation between conservation and AU/GC content, whereas plant miRNAs show a negative/positive correlation between conservation and AU/GC content. Further analysis puts forward the hypothesis that the introns of protein-coding genes may be a main driving force for the origin and evolution of mammalian miRNAs. At the 5′ end, conserved miRNAs have a preference for base U, while less-conserved miRNAs have a preference for a non-U base in mammals. This difference does not exist in insects and plants, in which both conserved miRNAs and less-conserved miRNAs have a preference for base U at the 5′ end. We further revealed that the non-U preference at the 5′ end of less-conserved mammalian miRNAs is associated with miRNA function diversity, which may have evolved from the pressure of a highly sophisticated environmental stimulus the mammals encountered during evolution. These results indicated that miRNA sequences contain the fingerprints for conservation, and these fingerprints vary according to species. More importantly, the results suggest that although species share common mechanisms by which miRNAs originate and evolve, mammals may develop a novel mechanism for miRNA origin and evolution. In addition, the fingerprint found in this study can be predictor of miRNA conservation, and the findings are helpful in achieving a

  13. Role of microRNAs on adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity.

    PubMed

    Cruz, Kyria Jayanne Clímaco; de Oliveira, Ana Raquel Soares; Morais, Jennifer Beatriz Silva; Severo, Juliana Soares; Marreiro PhD, Dilina do Nascimento

    2017-03-01

    The aim of this review was to convey updated information on the role of microRNAs in adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity. Obesity is a chronic disease characterized by the presence of metabolic disorders (e.g., low-grade chronic inflammation), which contributes to the manifestation of insulin resistance. Diverse molecular mechanisms have been implicated in the development of these disorders, and microRNAs stand out as a contributing factor. They are a class of noncoding RNAs that regulate the expression of genes by inducing cleavage of mRNAs or via inhibition of protein translation. It is important to point out that obese individuals show alterations in the expression of microRNAs favoring manifestation of the metabolic disorders present in these patients, and these alterations may be reversed by the loss of weight. Therefore, microRNAs may be regarded as potential biomarkers of obesity-related disorders. Further studies on this topic may advance the understanding of the molecular basis of obesity, including the participation of microRNAs in the pathogenesis of this disease.

  14. Sexually Dimorphic Effects of Gestational Endocrine-Disrupting Chemicals on MicroRNA Expression in the Developing Rat Hypothalamus

    PubMed Central

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

    2015-01-01

    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. PMID:26190835

  15. The expression of a viral microRNA is regulated by clustering to allow optimal B cell transformation

    PubMed Central

    Haar, Janina; Contrant, Maud; Bernhardt, Katharina; Feederle, Regina; Diederichs, Sven; Pfeffer, Sébastien; Delecluse, Henri-Jacques

    2016-01-01

    The Epstein-Barr virus (EBV) transforms B cells by expressing latent proteins and the BHRF1 microRNA cluster. MiR-BHRF1–3, its most transforming member, belongs to the recently identified group of weakly expressed microRNAs. We show here that miR-BHRF1–3 displays an unusually low propensity to form a stem–loop structure, an effect potentiated by miR-BHRF1–3's proximity to the BHRF1 polyA site. Cloning miR-BHRF1–2 or a cellular microRNA, but not a ribozyme, 5′ of miR-BHRF1–3 markedly enhanced its expression. However, a virus carrying mutated miR-BHRF1–2 seed regions expressed miR-BHRF1–3 at normal levels and was fully transforming. Therefore, miR-BHRF1–2's role during transformation is independent of its seed regions, revealing a new microRNA function. Increasing the distance between miR-BHRF1–2 and miR-BHRF1–3 in EBV enhanced miR-BHRF1–3's expression but decreased its transforming potential. Thus, the expression of some microRNAs must be restricted to a narrow range, as achieved by placing miR-BHRF1–3 under the control of miR-BHRF1–2. PMID:26635399

  16. Kaposi's Sarcoma Herpesvirus MicroRNAs Induce Metabolic Transformation of Infected Cells

    PubMed Central

    Yogev, Ohad; Lagos, Dimitris; Enver, Tariq; Boshoff, Chris

    2014-01-01

    Altered cell metabolism is inherently connected with pathological conditions including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KS tumour cells display features of lymphatic endothelial differentiation and in their vast majority are latently infected with KSHV, while a small number are lytically infected, producing virions. Latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, the metabolic properties of KSHV-infected cells closely resemble the metabolic hallmarks of cancer cells. However, how and why KSHV alters host cell metabolism remains poorly understood. Here, we investigated the effect of KSHV infection on the metabolic profile of primary dermal microvascular lymphatic endothelial cells (LEC) and the functional relevance of this effect. We found that the KSHV microRNAs within the oncogenic cluster collaborate to decrease mitochondria biogenesis and to induce aerobic glycolysis in infected cells. KSHV microRNAs expression decreases oxygen consumption, increase lactate secretion and glucose uptake, stabilize HIF1α and decreases mitochondria copy number. Importantly this metabolic shift is important for latency maintenance and provides a growth advantage. Mechanistically we show that KSHV alters host cell energy metabolism through microRNA-mediated down regulation of EGLN2 and HSPA9. Our data suggest that the KSHV microRNAs induce a metabolic transformation by concurrent regulation of two independent pathways; transcriptional reprograming via HIF1 activation and reduction of mitochondria biogenesis through down regulation of the mitochondrial import machinery. These findings implicate viral microRNAs in the regulation of the cellular metabolism and highlight new potential avenues to inhibit viral latency. PMID:25255370

  17. Long-range RNA pairings contribute to mutually exclusive splicing.

    PubMed

    Yue, Yuan; Yang, Yun; Dai, Lanzhi; Cao, Guozheng; Chen, Ran; Hong, Weiling; Liu, Baoping; Shi, Yang; Meng, Yijun; Shi, Feng; Xiao, Mu; Jin, Yongfeng

    2016-01-01

    Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks.

  18. Sparse Bayesian Learning for DOA Estimation with Mutual Coupling

    PubMed Central

    Dai, Jisheng; Hu, Nan; Xu, Weichao; Chang, Chunqi

    2015-01-01

    Sparse Bayesian learning (SBL) has given renewed interest to the problem of direction-of-arrival (DOA) estimation. It is generally assumed that the measurement matrix in SBL is precisely known. Unfortunately, this assumption may be invalid in practice due to the imperfect manifold caused by unknown or misspecified mutual coupling. This paper describes a modified SBL method for joint estimation of DOAs and mutual coupling coefficients with uniform linear arrays (ULAs). Unlike the existing method that only uses stationary priors, our new approach utilizes a hierarchical form of the Student t prior to enforce the sparsity of the unknown signal more heavily. We also provide a distinct Bayesian inference for the expectation-maximization (EM) algorithm, which can update the mutual coupling coefficients more efficiently. Another difference is that our method uses an additional singular value decomposition (SVD) to reduce the computational complexity of the signal reconstruction process and the sensitivity to the measurement noise. PMID:26501284

  19. Arrays of mutually coupled receiver coils: theory and application.

    PubMed

    Wright, S M; Magin, R L; Kelton, J R

    1991-01-01

    Specialized receiver coils having a small sensitive region can provide an improvement in SNR for MR imaging and spectroscopy, at the expense of limiting the usable field of view. This work presents a technique for designing coil arrays that allows the size and location of the sensitive region to be selected remotely. Only one element of the coil array is directly connected to the receiver, allowing flexibility in system design and implementation. A method is presented for the analysis and design of mutually coupled coil arrays of any number of elements of arbitrary shape. The analysis includes mutual coupling effects between primary coils, to allow multiple primary coils to be used simultaneously. A controller system allows remote selection of the sensitive region and automatically matches the impedance of the array to the preamplifier. Results obtained using a mutually coupled coil array designed for spine imaging are shown.

  20. Homosexual mutuality: variation on a theme by Erik Erikson.

    PubMed

    Sohier, R

    The exploratory descriptive study described here was conducted in order to produce the initial empirical evidence to support reformulation of the theoretical construct of heterosexual mutuality (Erikson, 1975). Six persons were interviewed in depth on tape in order to locate them on one of four identity statuses constructed by Marcia (1964, 1966, 1973). The tool was modified and extended to meet the purposes of the study. The questions are directed toward illumination of conflictual moments in the life cycle when the ability to make appropriate decisions engenders character growth, and supports the personality integration of adulthood. An ability to make decisions results in personality integration. The small study provides evidence that there exists a homosexual mutuality (contrary to Erikson's position) which is no less valuable than heterosexual mutuality, and forms an equal basis for adult personality integration.

  1. Optical phase dynamics in mutually coupled diode laser systems exhibiting power synchronization

    NASA Astrophysics Data System (ADS)

    Pal, Vishwa; Prasad, Awadhesh; Ghosh, R.

    2011-12-01

    We probe the physical mechanism behind the known phenomenon of power synchronization of two diode lasers that are mutually coupled via their delayed optical fields. In a diode laser, the amplitude and the phase of the optical field are coupled by the so-called linewidth enhancement factor, α. In this work, we explore the role of optical phases of the electric fields in amplitude (and hence power) synchronization through α in such mutually delay-coupled diode laser systems. Our numerical results show that the synchronization of optical phases drives the powers of lasers to synchronized death regimes. We also find that as α varies for different diode lasers, the system goes through a sequence of in-phase amplitude-death states. Within the windows between successive amplitude-death regions, the cross-correlation between the field amplitudes exhibits a universal power-law behaviour with respect to α.

  2. Mutual potential between two rigid bodies with arbitrary shapes and mass distributions

    NASA Astrophysics Data System (ADS)

    Hou, Xiyun; Scheeres, Daniel J.; Xin, Xiaosheng

    2016-09-01

    Formulae to compute the mutual potential, force, and torque between two rigid bodies are given. These formulae are expressed in Cartesian coordinates using inertia integrals. They are valid for rigid bodies with arbitrary shapes and mass distributions. By using recursive relations, these formulae can be easily implemented on computers. Comparisons with previous studies show their superiority in computation speed. Using the algorithm as a tool, the planar problem of two ellipsoids is studied. Generally, potential truncated at the second order is good enough for a qualitative description of the mutual dynamics. However, for ellipsoids with very large non-spherical terms, higher order terms of the potential should be considered, at the cost of a higher computational cost. Explicit formulae of the potential truncated to the fourth order are given.

  3. Mutually exclusive sense–antisense transcription at FLC facilitates environmentally induced gene repression

    PubMed Central

    Rosa, Stefanie; Duncan, Susan; Dean, Caroline

    2016-01-01

    Antisense transcription through genic regions is pervasive in most genomes; however, its functional significance is still unclear. We are studying the role of antisense transcripts (COOLAIR) in the cold-induced, epigenetic silencing of Arabidopsis FLOWERING LOCUS C (FLC), a regulator of the transition to reproduction. Here we use single-molecule RNA FISH to address the mechanistic relationship of FLC and COOLAIR transcription at the cellular level. We demonstrate that while sense and antisense transcripts can co-occur in the same cell they are mutually exclusive at individual loci. Cold strongly upregulates COOLAIR transcription in an increased number of cells and through the mutually exclusive relationship facilitates shutdown of sense FLC transcription in cis. COOLAIR transcripts form dense clouds at each locus, acting to influence FLC transcription through changed H3K36me3 dynamics. These results may have general implications for other loci showing both sense and antisense transcription. PMID:27713408

  4. Mutual potential between two rigid bodies with arbitrary shapes and mass distributions

    NASA Astrophysics Data System (ADS)

    Hou, Xiyun; Scheeres, Daniel J.; Xin, Xiaosheng

    2017-03-01

    Formulae to compute the mutual potential, force, and torque between two rigid bodies are given. These formulae are expressed in Cartesian coordinates using inertia integrals. They are valid for rigid bodies with arbitrary shapes and mass distributions. By using recursive relations, these formulae can be easily implemented on computers. Comparisons with previous studies show their superiority in computation speed. Using the algorithm as a tool, the planar problem of two ellipsoids is studied. Generally, potential truncated at the second order is good enough for a qualitative description of the mutual dynamics. However, for ellipsoids with very large non-spherical terms, higher order terms of the potential should be considered, at the cost of a higher computational cost. Explicit formulae of the potential truncated to the fourth order are given.

  5. Plant-fungal ecology. Niche engineering demonstrates a latent capacity for fungal-algal mutualism.

    PubMed

    Hom, Erik F Y; Murray, Andrew W

    2014-07-04

    Mutualistic symbioses shape the evolution of species and ecosystems and catalyze the emergence of biological complexity, yet how such symbioses first form is unclear. We show that an obligate mutualism between the yeast Saccharomyces cerevisiae and the alga Chlamydomonas reinhardtii--two model eukaryotes with very different life histories--can arise spontaneously in an environment requiring reciprocal carbon and nitrogen exchange. This capacity for mutualism is phylogenetically broad, extending to other Chlamydomonas and fungal species. Furthermore, we witnessed the spontaneous association of Chlamydomonas algal cells physically interacting with filamentous fungi. These observations demonstrate that under specific conditions, environmental change induces free-living species to become obligate mutualists and establishes a set of experimentally tractable, phylogenetically related, synthetic systems for studying the evolution of symbiosis.

  6. Mutual Lewis acid-base interactions of cations and anions in ionic liquids.

    PubMed

    Holzweber, Markus; Lungwitz, Ralf; Doerfler, Denise; Spange, Stefan; Koel, Mihkel; Hutter, Herbert; Linert, Wolfgang

    2013-01-02

    Solute properties are known to be strongly influenced by solvent molecules due to solvation. This is due to mutual interaction as both the properties of the solute and of the solvent strongly depend on each other. The present paper is based on the idea that ionic liquids are cations solvated by anions and anions solvated by cations. To show this (in this system strongly pronounced) interaction the long time established donor-acceptor concept for solvents and ions in solution by Viktor Gutmann is extended to ionic liquids. A number of solvent parameters, such as the Kamlet-Abboud-Taft and the Dimroth-Reichardt E(T) scale for ionic liquids neglect this mutual influence, which, however, seems to be in fact necessary to get a proper description of ionic liquid properties. It is shown how strong such parameters vary when the influence of the counter ion is taken into account. Furthermore, acceptor and donor numbers for ionic liquids are presented.

  7. PRL-3 and E-cadherin show mutual interactions and participate in lymph node metastasis formation in gastric cancer.

    PubMed

    Pryczynicz, Anna; Guzińska-Ustymowicz, Katarzyna; Niewiarowska, Katarzyna; Cepowicz, Dariusz; Kemona, Andrzej

    2014-07-01

    E-cadherin, a transmembrane adhesion molecule, and phosphatase of regenerating liver 3 (PRL-3) protein, a member of the family of tyrosine phosphatases, seem to be responsible for cancer cell migration. Therefore, the study objective was to determine a correlation between PRL-3 and E-cadherin, to assess their expression in neoplastic tissue and normal mucosa of the stomach, to analyze their effect on cancer advancement, and to evaluate their potential as prognostic markers in gastric cancer. The expressions of PRL-3 and E-cadherin were assessed immunohistochemically in 71 patients with gastric cancer. Positive expression of PRL-3 was observed in 42.2 % of gastric cancer cases, whereas E-cadherin expression was abnormal in 38 % of cases. The study revealed that the positive PRL-3 expression and abnormal E-cadherin expression were associated with mucinous gastric carcinoma and lymph node involvement. The former was also related to the infiltrating type of tumor and abnormal E-cadherin expression. The expression of PRL-3, but not of E-cadherin, was associated with shorter survival of patients. PRL-3 and E-cadherin exhibit interactions in gastric cancer and are involved in the formation of lymph node metastases. The PRL-3 protein can be an independent predictive factor of overall survival in gastric cancer patients.

  8. Differentially expressed plasma microRNAs and the potential regulatory function of Let-7b in chronic thromboembolic pulmonary hypertension.

    PubMed

    Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X-J; Wang, Jun; Wang, Chen

    2014-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by

  9. Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X.-J.; Wang, Jun; Wang, Chen

    2014-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by

  10. MicroRNA networks regulate development of brown adipocytes.

    PubMed

    Trajkovski, Mirko; Lodish, Harvey

    2013-09-01

    Brown adipose tissue (BAT) is specialized for heat generation and energy expenditure as a defense against cold and obesity; in both humans and mice increased amounts of BAT are associated with a lean phenotype and resistance to development of the metabolic syndrome and its complications. Here we summarize recent research showing that several BAT-expressed microRNAs (miRNAs) play important roles in regulating differentiation and metabolism of brown and beige adipocytes; we discuss the key mRNA targets downregulated by these miRNAs and show how these miRNAs affect directly or indirectly transcription factors important for BAT development. We suggest that these miRNAs could be part of novel therapeutics to increase BAT in humans.

  11. Spatial heterogeneity and host repression in fig-fig wasp mutualism.

    PubMed

    Wang, RuiWu; Wen, XiaoLan; Chen, Chun; Shi, Lei; Compton, Stephen G

    2015-05-01

    It is generally believed that physical heterogeneity in common resource or evolutionary restraint can sufficiently prevent direct conflict between host and symbionts in mutualism systems. Our data on fig/fig wasp reciprocal mutualism (Ficus racemosa), however, show that structural barriers of female flowers or genetic constraints of pollinators previously hypothesized exist, but cannot sufficiently maintain the mutualism stability. The results show that a positive relationship between seed and wasp production could be maintained in warm season, which might be because of density dependence restraint among foundresses and their low oviposition and pollination efficiency, keeping common resource (female flowers) utilization unsaturated. Whilst, a negative correlation between wasp offspring and viable seed production was also observed in cold season, which might be that the increased oviposition and pollination efficiency maximized the common resource utilization. The fitness trade-off between fig and pollinator wasps is greatly affected by environmental or ecological variations. The local stability might result from temporal low exploitation efficiency of pollinators together with interference competition among pollinators. We suggest that host repression through the active regulation of bract closure, which can create interference competition among the foundresses and prevent extra more foundresses sequential entry in fruit cavities, would help the figs avoiding the cost of over-exploitation. This essentially takes the same role as sanctioning of cheating or competitive behaviors.

  12. Rapid evolution of stability and productivity at the origin of a microbial mutualism

    SciTech Connect

    Hillesland, Kristina L.; Stahl, David A.

    2009-12-01

    Mutualistic interactions are taxonomically and functionally diverse. Despite their ubiquity, the basic ecological and evolutionary processes underlying their origin and maintenance are poorly understood. A major reason for this has been the lack of an experimentally tractable model system. We examine the evolution of an experimentally imposed obligate mutualism between sulfate-reducing and methanogenic microorganisms that have no known history of prior interaction. Twenty-four independent pairings (cocultures) of the bacterium Desulfovibrio vulgaris and the archaeon Methanococcus maripaludis were established and followed for 300 community doublings in two environments, one allowing for the development of a heterogeneous distribution of resources and the other not. Evolved cocultures grew up to 80percent faster and were up to 30percent more productive (biomass yield per mole substrate) than the ancestors. The evolutionary process was marked by periods of significant instability leading to extinction of two of the cocultures, but resulted in more stable, efficient, and productive mutualisms for most replicated pairings. Comparisons of evolved cocultures with those assembled from one evolved and one ancestral mutualist showed that evolution of both species contributed to improved productivity. Surprisingly, however, overall improvements in growth rate and yield were less than the sum of individual contributions, suggesting antagonistic interactions between mutations from the coevolved populations. Physical constraints on the transfer of metabolites in the evolution environment affected the evolution of M. maripaludis but not D. vulgaris. Together, these results show that challenges can imperil nascent obligate mutualisms and demonstrate the evolutionary responses that enable their persistence and future evolution.

  13. Analysis of the Mutual Inductance Particle Velocimeter (MIPV)

    DTIC Science & Technology

    1974-11-01

    yKeU’v-T-.-’j-i^fi.T mmmmmm AD/A-004 219 ANALYSIS OF THE MUTUAL INDUCTANCE PARTICLE VELOCIMETER (MIPV) Joseph D. Renick Air Force...REPORT DOCUMENTATION PAGE 1. REPORT NUMBER AFWL-TR-74-205 2. GOVT ACCESSION NO 4. TITLE fand SubtUU.) ANALYSIS OF THE MUTUAL INDUCTANCE...Resistance as a Function of Stress for Several Metals 109 C-2 Geometry for One-Dimensional Shock Response Analysis HI C-3 Shock Equilibration of

  14. Analysis and Synthesis of Microstrip Antennas Including Mutual Coupling

    DTIC Science & Technology

    1988-09-01

    E N 11. TITLE (/b*I* Secwfty OuodlCaUOn~) Analysis and Synthesis of Microstrip Antennas Including Mutual Coupling 12. PERSONAL AUTHOR(S) K~oichiro...GROUP SUB-GROUP Array Antennas, Microstrip Antennas, Array Analysis, Array Synthesis, Array Theory, Microwave Network Analysi! 19. ABSTRACT (Continue...VIRGI-J~NIA TECH ANALYSIS AND SYNTHESIS OF [. MICROSTRIP ANTENNAS INCLUDING MUTUAL COUPLING o0000 0 0 a o 0 0 0 0 0 o 0 00 0 00 o00000 0o000 0 0 0 a 0 0 0o

  15. Biochemical Machines for the Interconversion of Mutual Information and Work

    NASA Astrophysics Data System (ADS)

    McGrath, Thomas; Jones, Nick S.; ten Wolde, Pieter Rein; Ouldridge, Thomas E.

    2017-01-01

    We propose a physically realizable information-driven device consisting of an enzyme in a chemical bath, interacting with pairs of molecules prepared in correlated states. These correlations persist without direct interaction and thus store free energy equal to the mutual information. The enzyme can harness this free energy, and that stored in the individual molecular states, to do chemical work. Alternatively, the enzyme can use the chemical driving to create mutual information. A modified system can function without external intervention, approaching biological systems more closely.

  16. Separability criteria via sets of mutually unbiased measurements.

    PubMed

    Liu, Lu; Gao, Ting; Yan, Fengli

    2015-08-17

    Mutually unbiased measurements (MUMs) are generalized from the concept of mutually unbiased bases (MUBs) and include the complete set of MUBs as a special case, but they are superior to MUBs as they do not need to be rank one projectors. We investigate entanglement detection using sets of MUMs and derive separability criteria for multipartite qudit systems, arbitrary high-dimensional bipartite systems of a d1-dimensional subsystem and a d2-dimensional subsystem, and multipartite systems of multi-level subsystems. These criteria are of the advantages of more effective and wider application range than previous criteria. They provide experimental implementation in detecting entanglement of unknown quantum states.

  17. microRNAs and cholesterol metabolism

    PubMed Central

    Moore, Kathryn J.; Rayner, Katey J.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2010-01-01

    Cholesterol metabolism is tightly regulated at the cellular level. In addition to classic transcriptional regulation of cholesterol metabolism (e.g., by SREBP and LXR), members of a class of non-coding RNAs termed microRNAs (miRNAs) have recently been identified to be potent post-transcriptional regulators of lipid metabolism genes, including cholesterol homeostasis. We and others have recently shown that miR-33 regulates cholesterol efflux and HDL biogenesis by downregulating the expression of the ABC transporters, ABCA1 and ABCG1. In addition to miR-33, miR-122 and miR-370 have been shown to play important roles in regulating cholesterol and fatty acid metabolism. These new data suggest important roles of microRNAs in the epigenetic regulation of cholesterol metabolism and have opened new avenues for the treatment of dyslipidemias. PMID:20880716

  18. MicroRNA inhibition fine-tunes and provides robustness to the restriction point switch of the cell cycle

    PubMed Central

    del Rosario, Ricardo C. H.; Damasco, Joseph Ray Clarence G.; Aguda, Baltazar D.

    2016-01-01

    The restriction point marks a switch in G1 from growth factor-dependent to growth factor-independent progression of the cell cycle. The proper regulation of this switch is important for normal cell processes; aberrations could result in a number of diseases such as cancer, neurodegenerative disorders, stroke and myocardial infarction. To further understand the regulation of the restriction point, we extended a mathematical model of the Rb-E2F pathway to include members of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs play an essential role in fine-tuning and providing robustness to the switch. We also demonstrate how microRNA regulation can steer cells in or out of cancer states. PMID:27610602

  19. Entanglement and nonclassicality: A mutual impression

    NASA Astrophysics Data System (ADS)

    Gholipour, H.; Shahandeh, F.

    2016-06-01

    We find a sufficient condition to imprint the single-mode bosonic phase-space nonclassicality onto a bipartite state as modal entanglement and vice versa using an arbitrary beam splitter. Surprisingly, the entanglement produced or detected in this way depends only on the nonclassicality of the marginal input or output states, regardless of their purity and separability. In this way, our result provides a sufficient condition for generating entangled states of arbitrary high temperature and arbitrary large number of particles. We also study the evolution of the entanglement within a lossy Mach-Zehnder interferometer and show that unless both modes are totally lost, the entanglement does not diminish.

  20. Viral hemorrhagic septicemia virus (VHSV) infection-mediated sequential changes in microRNAs profile of Epithelioma papulosum cyprini (EPC) cells.

    PubMed

    Najib, Abdellaoui; Kim, Min Sun; Kim, Ki Hong

    2017-02-01

    MicroRNAs are small non-coding RNAs and are involved in the regulation of wide biological processes. Viral hemorrhagic septicemia virus (VHSV) is the causative agent of viral hemorrhagic septicemia (VHS) disease causing a heavy loss in aquaculture farms. In this study, we tried to explore the effect of VHSV infection on microRNAs profile of Epithelioma papulosum cyprini (EPC) cells at different points of time (0, 3, 12, 24, and 48 h post infection). A total of 355 conserved microRNAs and 3 novel microRNAs were identified, and among them, 103 microRNAs were differentially expressed. The number of differentially expressed microRNAs was highly increased at 24 h.p.i compared to 3 h.p.i and 12 h.p.i., suggesting that EPC cells might not actively respond to VHSV infection at an early infection period, which can allow viruses to transcript and translate their genes enough to produce viral particles that can infect to another cells. Among the differentially expressed microRNAs, 2 miRNAs (miR-735 and miR-738) that were reported only in fish species were highly upregulated, and based on the target prediction, they could regulate several immune pathways. Furthermore, the present results showed the upregulation of representative immune regulating microRNAs such as miR-146a, miR-155, and miR-99. The target prediction of differentially expressed miRNAs, GO, and KEGG pathways analysis revealed that several biological processes and different pathways were affected by the viral infection. The present dynamical changing patterns of differentially expressed microRNAs in response to the progression of VHSV infection suggest that microRNA profile that was analyzed at one time point cannot provide enough information for the interpretation of the disease mechanism. Considering the wide and complex interactions between microRNAs and genes expression, the present results provide the basis for the understanding of VHSV infection-mediated cellular responses and for future investigations

  1. Effects of short-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on microRNA expression in zebrafish embryos

    SciTech Connect

    Jenny, Matthew J.; Aluru, Neelakanteswar; Hahn, Mark E.

    2012-10-15

    Although many drugs and environmental chemicals are teratogenic, the mechanisms by which most toxicants disrupt embryonic development are not well understood. MicroRNAs, single-stranded RNA molecules of ∼ 22 nt that regulate protein expression by inhibiting mRNA translation and promoting mRNA sequestration or degradation, are important regulators of a variety of cellular processes including embryonic development and cellular differentiation. Recent studies have demonstrated that exposure to xenobiotics can alter microRNA expression and contribute to the mechanisms by which environmental chemicals disrupt embryonic development. In this study we tested the hypothesis that developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a well-known teratogen, alters microRNA expression during zebrafish development. We exposed zebrafish embryos to DMSO (0.1%) or TCDD (5 nM) for 1 h at 30 hours post fertilization (hpf) and measured microRNA expression using several methods at 36 and 60 hpf. TCDD caused strong induction of CYP1A at 36 hpf (62-fold) and 60 hpf (135-fold) as determined by real-time RT-PCR, verifying the effectiveness of the exposure. MicroRNA expression profiles were determined using microarrays (Agilent and Exiqon), next-generation sequencing (SOLiD), and real-time RT-PCR. The two microarray platforms yielded results that were similar but not identical; both showed significant changes in expression of miR-451, 23a, 23b, 24 and 27e at 60 hpf. Multiple analyses were performed on the SOLiD sequences yielding a total of 16 microRNAs as differentially expressed by TCDD in zebrafish embryos. However, miR-27e was the only microRNA to be identified as differentially expressed by all three methods (both microarrays, SOLiD sequencing, and real-time RT-PCR). These results suggest that TCDD exposure causes modest changes in expression of microRNAs, including some (miR-451, 23a, 23b, 24 and 27e) that are critical for hematopoiesis and cardiovascular

  2. Increased microRNA-155 and decreased microRNA-146a may promote ocular inflammation and proliferation in Graves' ophthalmopathy.

    PubMed

    Li, Kaijun; Du, Yi; Jiang, Ben-Li; He, Jian-Feng

    2014-04-18

    Graves' ophthalmopathy is an inflammatory autoimmune disease of the orbit, characterized by inflammation and proliferation of the orbital tissue caused by CD4+T cells and orbital fibroblasts. Despite recent substantial findings regarding its cellular and molecular foundations, the pathogenesis of Graves' ophthalmopathy remains unclear. Accumulating data suggest that microRNAs play important roles in the pathophysiology of autoimmunity and proliferation. Specifically, microRNA-155 (miR-155) can promote autoimmune inflammation by enhancing inflammatory T cell development. In contrast to miR-155, microRNA-146a (miR-146a) can inhibit the immune response by suppressing T cell activation. Furthermore, miR-155 and miR-146a are involved in cell proliferation, differentiation, and many other life processes. Thus, miR-155 and miR-146a, with opposite impacts on inflammatory responses carried out by T lymphocytes, appear to have multiple targets in the pathogenesis of Graves' ophthalmopathy. Our previous work showed that the expression of miR-146a was significantly decreased in peripheral blood mononuclear cells from Graves' ophthalmopathy patients compared with normal subjects. Accordingly, we proposed that the expression of miR-155 increased and the expression of miR-146a decreased in the target cells (CD4+T cells and orbital fibroblasts), thus promoting ocular inflammation and proliferation in Graves' ophthalmopathy. The proposed hypothesis warrants further investigation of the function of the differentially expressed microRNAs, which may shed new light on the pathogenesis of Graves' ophthalmopathy and lead to new strategies for its management.

  3. A Mutual Support Group for Young Problem Gamblers

    ERIC Educational Resources Information Center

    Binde, Per

    2012-01-01

    A Swedish mutual support group for young problem gamblers is described and discussed. During the study period, 116 weekly meetings occurred, usually involving six to ten participants; in total, 69 problem gamblers (66 male and three female), aged 17-25, and 23 partners and friends attended the meetings. Half the gamblers had problems with Internet…

  4. 77 FR 48566 - The Hartford Mutual Funds, Inc., et al.;

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION The Hartford Mutual Funds, Inc., et al.; Notice of Application August 8, 2012. AGENCY: Securities and Exchange Commission (``Commission''). ACTION: Notice of an application under section 6(c) of...

  5. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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... not available in other bands. During the initial filing window, frequency coordination is not...

  6. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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... not available in other bands. During the initial filing window, frequency coordination is not...

  7. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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... not available in other bands. During the initial filing window, frequency coordination is not...

  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... not available in other bands. During the initial filing window, frequency coordination is not...

  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... not available in other bands. During the initial filing window, frequency coordination is not...

  10. Mutual Funds as a Form of Collective Investment in Russia

    ERIC Educational Resources Information Center

    Tershukova, Marina B.; Savinov, Oleg G.; Zhegalova, Elena V.; Zhuruhinc, Georgy I.; Zhegalova, Alexandra S.

    2016-01-01

    The relevance of the research problem inspired with the fact nowadays there is a need for theoretical generalization based on international experience the essence of the collective investment system and the rationale for prioritizing the mutual funds development as the most attractive form of collective investment. The goal of the article lies in…

  11. Is Action Research Necessarily Collaborative? Changing Mutuality within a Project

    ERIC Educational Resources Information Center

    Sousa, Francisco

    2016-01-01

    This article reports a study on collaboration within an action research project that was conducted by university researchers and elementary school teachers in the Azores, Portugal. More specifically, it examines how different kinds of participants worked together in different phases of the project. The notion of mutuality (i.e., the relative…

  12. Mutual Intercultural Relations among University Students in Canada

    ERIC Educational Resources Information Center

    Gui, Yongxia; Safdar, Saba; Berry, John

    2016-01-01

    The current study examies the views of both international and domestic students in Canada using the conceptual and empirical framework from the MIRIPS (Mutual Intercultural Relations in Plural Societies) project (http://www.victoria.ac.nz/cacr/research/mirips). Two hypotheses were examined. First is the "multiculturalism hypothesis"…

  13. Mutual information area laws for thermal free fermions

    NASA Astrophysics Data System (ADS)

    Bernigau, H.; Kastoryano, M. J.; Eisert, J.

    2015-02-01

    We provide a rigorous and asymptotically exact expression of the mutual information of translationally invariant free fermionic lattice systems in a Gibbs state. In order to arrive at this result, we introduce a novel framework for computing determinants of Töplitz operators with smooth symbols, and for treating Töplitz matrices with system size dependent entries. The asymptotically exact mutual information for a partition of the 1D lattice satisfies an area law, with a prefactor which we compute explicitly. As examples, we discuss the fermionic XX model in one dimension and free fermionic models on the torus in higher dimensions in detail. Special emphasis is put on the discussion of the temperature dependence of the mutual information, scaling like the logarithm of the inverse temperature, hence confirming an expression suggested by conformal field theory. We also comment on the applicability of the formalism to treat open systems driven by quantum noise. In the appendix, we derive useful bounds to the mutual information in terms of purities. Finally, we provide a detailed error analysis for finite system sizes. This analysis is valuable in its own right for the abstract theory of Töplitz determinants.

  14. Mutual Aid: A Key to Survival for Black Americans

    ERIC Educational Resources Information Center

    Norman, Alex J.

    1977-01-01

    In the Brotherhood Crusade, a black mutual aid, self-help organization, Los Angeles blacks joined together to effect independence within the professions and the social service delivery systems, rejecting incorporation into the United Way, the major L.A. fund-raising organization. This article presents findings of a study of Crusade participants.…

  15. 12 CFR 563.74 - Mutual capital certificates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... dividend may be paid if such payment would constitute a violation of 12 U.S.C. 1828(b); (v) Not be... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Mutual capital certificates. 563.74 Section 563... of filing of the application are in accordance with the provisions of this section. (b)...

  16. 12 CFR 563.74 - Mutual capital certificates.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... dividend may be paid if such payment would constitute a violation of 12 U.S.C. 1828(b); (v) Not be... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Mutual capital certificates. 563.74 Section 563... of filing of the application are in accordance with the provisions of this section. (b)...

  17. 12 CFR 544.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... by the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  18. 12 CFR 144.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the institution... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  19. 12 CFR 544.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... by the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  20. 12 CFR 144.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the institution... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  1. 12 CFR 544.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... by the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  2. 12 CFR 144.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the institution... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  3. 12 CFR 544.5 - Federal mutual savings association bylaws.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... by the association. (3) Corporate governance procedures. A Federal mutual association may elect to follow the corporate governance procedures of the laws of the state where the main office of the... corporate governance procedures, and shall file a copy of such bylaws, which are effective upon...

  4. Using Mutual Information for Adaptive Item Comparison and Student Assessment

    ERIC Educational Resources Information Center

    Liu, Chao-Lin

    2005-01-01

    The author analyzes properties of mutual information between dichotomous concepts and test items. The properties generalize some common intuitions about item comparison, and provide principled foundations for designing item-selection heuristics for student assessment in computer-assisted educational systems. The proposed item-selection strategies…

  5. International Mutual Recognition: Progress and Prospects. Working Paper.

    ERIC Educational Resources Information Center

    Hager, Paul

    Increasing the mobility of service providers, including professionals, via mutual recognition (of regulatory systems) agreements (MRAs) has become a significant issue worldwide. Despite increasing interest in MRAs, it may be argued that MRAs are but one of a larger range of major developments that have fueled current interest in occupational…

  6. Mutual Suppression: Comment on Paulhus et Al. (2004)

    ERIC Educational Resources Information Center

    Nickerson, Carol

    2008-01-01

    Paulhus, Robins, Trzesniewski, and Tracy ("Multivariate Behavioral Research," 2004, 39, 305-328) suggested that the three types of two-predictor suppression situations--classical suppression, cooperative suppression, and net suppression--can all be considered special cases of mutual suppression, in that the magnitude of each of the two…

  7. The blind leading the blind: Mutual refinement of approximate theories

    NASA Technical Reports Server (NTRS)

    Kedar, Smadar T.; Bresina, John L.; Dent, C. Lisa

    1991-01-01

    The mutual refinement theory, a method for refining world models in a reactive system, is described. The method detects failures, explains their causes, and repairs the approximate models which cause the failures. The approach focuses on using one approximate model to refine another.

  8. Mutual Information Item Selection in Adaptive Classification Testing

    ERIC Educational Resources Information Center

    Weissman, Alexander

    2007-01-01

    A general approach for item selection in adaptive multiple-category classification tests is provided. The approach uses mutual information (MI), a special case of the Kullback-Leibler distance, or relative entropy. MI works efficiently with the sequential probability ratio test and alleviates the difficulties encountered with using other local-…

  9. Multi-Transiting Systems and Exoplanet Mutual Events

    NASA Astrophysics Data System (ADS)

    Coughlin, Jared; Ragozzine, D.; Holman, M. J.

    2011-01-01

    Until recently, studies of transiting exoplanets- planets that cross in front of their host star- have focused almost exclusively upon systems where there is only one transiting planet. Those studies that have considered additional planets have mostly done so with the goal of determining the perturbing effects that additional planets would have upon the orbit, and therefore the light curve, of the transiting planet. This work considers, in detail, a specific type of event known as an exoplanet mutual event. Such events occur when one planet passes in front of another. While such events can occur whether or not these planets are transiting, predicting and understanding these events is best done in systems with multiple transiting planets. We estimate, through an ensemble simulation, how frequently exoplanet mutual events occur and which systems are most likely to undergo exoplanet mutual events. We also investigate what information can be learned about not only the planets themselves but also the orbital architecture in such systems. We conclude that while ODT (overlapping double-transit) events occur with a much lower frequency than PPO (planet-planet occultation) events, ODT mutual events are capable of producing detectable signals, that Kepler will detect a few, and recommend that candidate systems for these events, such as KOI 191, be observed in short cadence(Steffen et. al 2010, Holman et. al 2010). This work is supported in part by the NSF REU and DOD ASSURE programs under NSF grant no. 0754568 and by the Smithsonian Institution.

  10. Mutual information in a dilute, asymmetric neural network model

    NASA Astrophysics Data System (ADS)

    Greenfield, Elliot

    We study the computational properties of a neural network consisting of binary neurons with dilute asymmetric synaptic connections. This simple model allows us to simulate large networks which can reflect more of the architecture and dynamics of real neural networks. Our main goal is to determine the dynamical behavior that maximizes the network's ability to perform computations. To this end, we apply information theory, measuring the average mutual information between pairs of pre- and post-synaptic neurons. Communication of information between neurons is an essential requirement for collective computation. Previous workers have demonstrated that neural networks with asymmetric connections undergo a transition from ordered to chaotic behavior as certain network parameters, such as the connectivity, are changed. We find that the average mutual information has a peak near the order-chaos transition, implying that the network can most efficiently communicate information between cells in this region. The mutual information peak becomes increasingly pronounced when the basic model is extended to incorporate more biologically realistic features, such as a variable threshold and nonlinear summation of inputs. We find that the peak in mutual information near the phase transition is a robust feature of the system for a wide range of assumptions about post-synaptic integration.

  11. A Swedish Mutual Support Society of Problem Gamblers

    ERIC Educational Resources Information Center

    Binde, Per

    2012-01-01

    Mutual support societies for problem gamblers have existed in Sweden for 20 years. They have helped more people with gambling problems than any other institution inside or outside the Swedish health care system. This paper outlines the background of these societies and describes the meetings of one of them. Data come from interviews with members…

  12. Antagonists in Mutual Antipathies: A Person-Oriented Approach

    ERIC Educational Resources Information Center

    Guroglu, Berna; Haselager, Gerbert J. T.; van Lieshout, Cornelis F. M.; Scholte, Ron H. J.

    2009-01-01

    This study investigated the heterogeneity of mutual antipathy relationships. Separate cluster analyses of peer interactions of early adolescents (mean age 11 years) and adolescents (mean age of 14) yielded 3 "types of individuals" in each age group, namely Prosocial, Antisocial, and Withdrawn. Prevalence analysis of the 6 possible combinations of…

  13. Evolution of the Fusarium–Euwallacea ambrosia beetle mutualism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Euwallacea – Fusarium mutualistic symbiosis represents one of the independent evolutionary origins of fungus-farming. Diversification time estimates place the evolutionary origin of this mutualism in the early Miocene approximately 21 million years ago. Fusarium is best known as one of the most ...

  14. Synchronization and symmetry breaking in mutually coupled fiber lasers.

    PubMed

    Rogers-Dakin, Elizabeth A; García-Ojalvo, Jordi; DeShazer, David J; Roy, Rajarshi

    2006-04-01

    We experimentally study the synchronization and the emergence of leader-follower dynamics in two time-delayed mutually coupled fiber ring lasers. We utilize spatiotemporal representations of time series to establish the roles of leader and follower in the synchronized dynamics.

  15. Synchronization and symmetry breaking in mutually coupled fiber lasers

    NASA Astrophysics Data System (ADS)

    Rogers-Dakin, Elizabeth A.; García-Ojalvo, Jordi; Deshazer, David J.; Roy, Rajarshi

    2006-04-01

    We experimentally study the synchronization and the emergence of leader-follower dynamics in two time-delayed mutually coupled fiber ring lasers. We utilize spatiotemporal representations of time series to establish the roles of leader and follower in the synchronized dynamics.

  16. Ecological genomics of mutualism decline in nitrogen-fixing bacteria

    PubMed Central

    Klinger, Christie R.; Lau, Jennifer A.

    2016-01-01

    Anthropogenic changes can influence mutualism evolution; however, the genomic regions underpinning mutualism that are most affected by environmental change are generally unknown, even in well-studied model mutualisms like the interaction between legumes and their nitrogen (N)-fixing rhizobia. Such genomic information can shed light on the agents and targets of selection maintaining cooperation in nature. We recently demonstrated that N-fertilization has caused an evolutionary decline in mutualistic partner quality in the rhizobia that form symbiosis with clover. Here, population genomic analyses of N-fertilized versus control rhizobium populations indicate that evolutionary differentiation at a key symbiosis gene region on the symbiotic plasmid (pSym) contributes to partner quality decline. Moreover, patterns of genetic variation at selected loci were consistent with recent positive selection within N-fertilized environments, suggesting that N-rich environments might select for less beneficial rhizobia. By studying the molecular population genomics of a natural bacterial population within a long-term ecological field experiment, we find that: (i) the N environment is indeed a potent selective force mediating mutualism evolution in this symbiosis, (ii) natural variation in rhizobium partner quality is mediated in part by key symbiosis genes on the symbiotic plasmid, and (iii) differentiation at selected genes occurred in the context of otherwise recombining genomes, resembling eukaryotic models of adaptation. PMID:26962142

  17. Changes in microRNAs expression profile of olive flounder (Paralichthys olivaceus) in response to viral hemorrhagic septicemia virus (VHSV) infection.

    PubMed

    Najib, Abdellaoui; Kim, Min Sun; Choi, Seung Hyuk; Kang, Yue Jai; Kim, Ki Hong

    2016-04-01

    To know the effect of viral hemorrhagic septicemia virus (VHSV) infection on the cellular microRNA expression profile in olive flounder (Paralichthys olivaceus), fish were infected with VHSV, and cellular microRNAs expression was analyzed at 0 (control), 6, 12, 24, 48 and 72 h post-infection (h.p.i.) by the high-throughput sequencing. A total of 372 mature miRNAs were identified, and, among them, 63 miRNAs were differentially expressed during VHSV infection. The differentially expressed microRNAs number was greatly increased from 24 h.p.i. compared to the number at 6 and 12 h.p.i., suggesting that the alteration of microRNAs expression by VHSV infection may be related to the progression of VHSV disease. The target prediction analysis, the GO enrichment analysis, and the KEGG pathway analysis of the predicted target genes showed that various biological pathways could be affected by VHSV infection through the down-regulation or up-regulation of host miRNAs. The present results provide a basic information on the microRNAs related to VHSV infection in olive flounder. Considering broad effects of microRNAs on various biological pathways, data in this study can be used to interpret the mechanism of VHSV pathogenesis, which, vice versa, can be used to develop control measures against VHSV.

  18. Three Drosophila Hox Complex microRNAs Do Not Have Major Effects on Expression of Evolutionarily Conserved Hox Gene Targets during Embryogenesis

    PubMed Central

    Lemons, Derek; Paré, Adam; McGinnis, William

    2012-01-01

    The discovery of microRNAs has resulted in a major expansion of the number of molecules known to be involved in gene regulation. Elucidating the functions of animal microRNAs has posed a significant challenge as their target interactions with messenger RNAs do not adhere to simple rules. Of the thousands of known animal microRNAs, relatively few microRNA:messenger RNA regulatory interactions have been biologically validated in an normal organismal context. Here we present evidence that three microRNAs from the Hox complex in Drosophila (miR-10-5p, miR-10-3p, miR-iab-4-5p) do not have significant effects during embryogenesis on the expression of Hox genes that contain high confidence microRNAs target sites in the 3′ untranslated regions of their messenger RNAs. This is significant, in that it suggests that many predicted microRNA-target interactions may not be biologically relevant, or that the outcomes of these interactions may be so subtle that mutants may only show phenotypes in specific contexts, such as in environmental stress conditions, or in combinations with other microRNA mutations. PMID:22393361

  19. Comparative evaluation of multiresolution optimization strategies for multimodality image registration by maximization of mutual information.

    PubMed

    Maes, F; Vandermeulen, D; Suetens, P

    1999-12-01

    Maximization of mutual information of voxel intensities has been demonstrated to be a very powerful criterion for three-dimensional medical image registration, allowing robust and accurate fully automated affine registration of multimodal images in a variety of applications, without the need for segmentation or other preprocessing of the images. In this paper, we investigate the performance of various optimization methods and multiresolution strategies for maximization of mutual information, aiming at increasing registration speed when matching large high-resolution images. We show that mutual information is a continuous function of the affine registration parameters when appropriate interpolation is used and we derive analytic expressions of its derivatives that allow numerically exact evaluation of its gradient. Various multiresolution gradient- and non-gradient-based optimization strategies, such as Powell, simplex, steepest-descent, conjugate-gradient, quasi-Newton and Levenberg-Marquardt methods, are evaluated for registration of computed tomography (CT) and magnetic resonance images of the brain. Speed-ups of a factor of 3 on average compared to Powell's method at full resolution are achieved with similar precision and without a loss of robustness with the simplex, conjugate-gradient and Levenberg-Marquardt method using a two-level multiresolution scheme. Large data sets such as 256(2) x 128 MR and 512(2) x 48 CT images can be registered with subvoxel precision in <5 min CPU time on current workstations.

  20. Robust Feature Selection from Microarray Data Based on Cooperative Game Theory and Qualitative Mutual Information

    PubMed Central

    Mortazavi, Atiyeh; Moattar, Mohammad Hossein

    2016-01-01

    High dimensionality of microarray data sets may lead to low efficiency and overfitting. In this paper, a multiphase cooperative game theoretic feature selection approach is proposed for microarray data classification. In the first phase, due to high dimension of microarray data sets, the features are reduced using one of the two filter-based feature selection methods, namely, mutual information and Fisher ratio. In the second phase, Shapley index is used to evaluate the power of each feature. The main innovation of the proposed approach is to employ Qualitative Mutual Information (QMI) for this purpose. The idea of Qualitative Mutual Information causes the selected features to have more stability and this stability helps to deal with the problem of data imbalance and scarcity. In the third phase, a forward selection scheme is applied which uses a scoring function to weight each feature. The performance of the proposed method is compared with other popular feature selection algorithms such as Fisher ratio, minimum redundancy maximum relevance, and previous works on cooperative game based feature selection. The average classification accuracy on eleven microarray data sets shows that the proposed method improves both average accuracy and average stability compared to other approaches. PMID:27127506

  1. Conflict of interest in a mutualism: documenting the elusive fig wasp-seed trade-off

    PubMed Central

    Herre, E. A.; West, S. A.

    1997-01-01

    The generally accepted view that mutualisms represent reciprocal exploitations implies a greater or lesser degree of inherent tension between the partners. This view emphasizes the importance of identifying conflicts of interest between the partners, and then attempting to quantify the effects of factors that influence costs and benefits to each. The natural history of the speciose fig-fig wasp pollination mutualisms permits such measurements. However, previous attempts to document the presumed tensions, which are expected to result in a negative relationship between the production of viable seeds and pollinator wasp offspring, have met with mixed results, casting doubt on the existence of the conflict. Here, we present hierarchical analyses of 929 fruits sampled from 30 crops representing nine species of monoecious New World figs. These analyses control for the confounding influences of variation in (1) pollination intensity (numbers of foundress pollinators); (2) flower number per fruit; and (3) the proportion of those flowers that develop, on seed and wasp production, both among and within crops. We thereby show that a negative relationship between the production of viable seeds and wasps is, in fact, ubiquitous, thus documenting this underlying tension inherent in the mutualism. We suggest that complex interactions of variables that influence costs and benefits are likely to be a general property of most mutualistic systems.

  2. The demographic consequences of mutualism: ants increase host-plant fruit production but not population growth.

    PubMed

    Ford, Kevin R; Ness, Joshua H; Bronstein, Judith L; Morris, William F

    2015-10-01

    The impact of mutualists on a partner's demography depends on how they affect the partner's multiple vital rates and how those vital rates, in turn, affect population growth. However, mutualism studies rarely measure effects on multiple vital rates or integrate them to assess the ultimate impact on population growth. We used vital rate data, population models and simulations of long-term population dynamics to quantify the demographic impact of a guild of ant species on the plant Ferocactus wislizeni. The ants feed at the plant's extrafloral nectaries and attack herbivores attempting to consume reproductive organs. Ant-guarded plants produced significantly more fruit, but ants had no significant effect on individual growth or survival. After integrating ant effects across these vital rates, we found that projected population growth was not significantly different between unguarded and ant-guarded plants because population growth was only weakly influenced by differences in fruit production (though strongly influenced by differences in individual growth and survival). However, simulations showed that ants could positively affect long-term plant population dynamics through services provided during rare but important events (herbivore outbreaks that reduce survival or years of high seedling recruitment associated with abundant precipitation). Thus, in this seemingly clear example of mutualism, the interaction may actually yield no clear benefit to plant population growth, or if it does, may only do so through the actions of the ants during rare events. These insights demonstrate the value of taking a demographic approach to studying the consequences of mutualism.

  3. Robust Feature Selection from Microarray Data Based on Cooperative Game Theory and Qualitative Mutual Information.

    PubMed

    Mortazavi, Atiyeh; Moattar, Mohammad Hossein

    2016-01-01

    High dimensionality of microarray data sets may lead to low efficiency and overfitting. In this paper, a multiphase cooperative game theoretic feature selection approach is proposed for microarray data classification. In the first phase, due to high dimension of microarray data sets, the features are reduced using one of the two filter-based feature selection methods, namely, mutual information and Fisher ratio. In the second phase, Shapley index is used to evaluate the power of each feature. The main innovation of the proposed approach is to employ Qualitative Mutual Information (QMI) for this purpose. The idea of Qualitative Mutual Information causes the selected features to have more stability and this stability helps to deal with the problem of data imbalance and scarcity. In the third phase, a forward selection scheme is applied which uses a scoring function to weight each feature. The performance of the proposed method is compared with other popular feature selection algorithms such as Fisher ratio, minimum redundancy maximum relevance, and previous works on cooperative game based feature selection. The average classification accuracy on eleven microarray data sets shows that the proposed method improves both average accuracy and average stability compared to other approaches.

  4. An efficient and adaptive mutual authentication framework for heterogeneous wireless sensor network-based applications.

    PubMed

    Kumar, Pardeep; Ylianttila, Mika; Gurtov, Andrei; Lee, Sang-Gon; Lee, Hoon-Jae

    2014-02-11

    Robust security is highly coveted in real wireless sensor network (WSN) applications since wireless sensors' sense critical data from the application environment. This article presents an efficient and adaptive mutual authentication framework that suits real heterogeneous WSN-based applications (such as smart homes, industrial environments, smart grids, and healthcare monitoring). The proposed framework offers: (i) key initialization; (ii) secure network (cluster) formation (i.e., mutual authentication and dynamic key establishment); (iii) key revocation; and (iv) new node addition into the network. The correctness of the proposed scheme is formally verified. An extensive analysis shows the proposed scheme coupled with message confidentiality, mutual authentication and dynamic session key establishment, node privacy, and message freshness. Moreover, the preliminary study also reveals the proposed framework is secure against popular types of attacks, such as impersonation attacks, man-in-the-middle attacks, replay attacks, and information-leakage attacks. As a result, we believe the proposed framework achieves efficiency at reasonable computation and communication costs and it can be a safeguard to real heterogeneous WSN applications.

  5. Influence of mutual coupling between ICRH antenna straps on the load resilience of hybrid couplers

    SciTech Connect

    Lamalle, P. U.; Messiaen, A.

    2007-09-28

    The mutual coupling present between ICRF antenna straps can strongly reduce the performance of quadrature hybrid couplers when used as 'ELM dump' circuits. An analytical study of this effect shows that during resistive ELM-like load perturbations of a matched circuit configuration, the fraction of the reflected power returned to the generator through the hybrid has a lower bound that rapidly increases with the ratio {xi}{approx} (mutual reactance between straps)/(strap input resistance). At very low levels of mutual the reflected power is efficiently diverted to the dummy load. However when {xi} becomes of order 1, which readily occurs at low resistive loading, the load resilience of the quadrature hybrid coupler becomes inhibited. Illustrations based on matching circuit simulations for the JET ITER-like ICRF antenna are presented. The behaviour of the hybrids is found the same with the load resilient 'conjugate T' circuit as in the case of 'classic' tuners. The insertion of decoupling circuits between the tuners and the antenna significantly improves the load resilience.

  6. Seed odor mediates an obligate ant–plant mutualism in Amazonian rainforests

    PubMed Central

    Youngsteadt, Elsa; Nojima, Satoshi; Häberlein, Christopher; Schulz, Stefan; Schal, Coby

    2008-01-01

    Seed dispersal mutualisms are essential for the survival of diverse plant species and communities worldwide. Among invertebrates, only ants have a major role in seed dispersal, and thousands of plant species produce seeds specialized for ant dispersal in “diffuse” multispecies interactions. An outstanding but poorly understood ant–seed mutualism occurs in the Amazonian rainforest, where arboreal ants collect seeds of several epiphyte species and cultivate them in nutrient-rich nests, forming abundant and conspicuous hanging gardens known as ant-gardens (AGs). AG ants and plants are dominant members of lowland Amazonian ecosystems, and their interaction is both specific and obligate, but the means by which ants locate, recognize, and accept their mutualist seeds while rejecting other seeds is unknown. Here we address the chemical and behavioral basis of the AG interaction. We show that workers of the AG ant Camponotus femoratus are attracted to odorants emanating from seeds of the AG plant Peperomia macrostachya, and that chemical cues also elicit seed-carrying behavior. We identify five compounds from P. macrostachya seeds that, as a blend, attract C. femoratus workers. This report of attractive odorants from ant-dispersed seeds illustrates the intimacy and complexity of the AG mutualism and begins to illuminate the chemical basis of this important and enigmatic interaction. PMID:18212122

  7. Influence of mutual coupling between ICRH antenna straps on the load resilience of hybrid couplers

    NASA Astrophysics Data System (ADS)

    Lamalle, P. U.; Messiaen, A.

    2007-09-01

    The mutual coupling present between ICRF antenna straps can strongly reduce the performance of quadrature hybrid couplers when used as "ELM dump" circuits. An analytical study of this effect shows that during resistive ELM-like load perturbations of a matched circuit configuration, the fraction of the reflected power returned to the generator through the hybrid has a lower bound that rapidly increases with the ratio ξ˜ (mutual reactance between straps)/(strap input resistance). At very low levels of mutual the reflected power is efficiently diverted to the dummy load. However when ξ becomes of order 1, which readily occurs at low resistive loading, the load resilience of the quadrature hybrid coupler becomes inhibited. Illustrations based on matching circuit simulations for the JET ITER-like ICRF antenna are presented. The behaviour of the hybrids is found the same with the load resilient `conjugate T' circuit as in the case of `classic' tuners. The insertion of decoupling circuits between the tuners and the antenna significantly improves the load resilience.

  8. An Efficient and Adaptive Mutual Authentication Framework for Heterogeneous Wireless Sensor Network-Based Applications

    PubMed Central

    Kumar, Pardeep; Ylianttila, Mika; Gurtov, Andrei; Lee, Sang-Gon; Lee, Hoon-Jae

    2014-01-01

    Robust security is highly coveted in real wireless sensor network (WSN) applications since wireless sensors' sense critical data from the application environment. This article presents an efficient and adaptive mutual authentication framework that suits real heterogeneous WSN-based applications (such as smart homes, industrial environments, smart grids, and healthcare monitoring). The proposed framework offers: (i) key initialization; (ii) secure network (cluster) formation (i.e., mutual authentication and dynamic key establishment); (iii) key revocation; and (iv) new node addition into the network. The correctness of the proposed scheme is formally verified. An extensive analysis shows the proposed scheme coupled with message confidentiality, mutual authentication and dynamic session key establishment, node privacy, and message freshness. Moreover, the preliminary study also reveals the proposed framework is secure against popular types of attacks, such as impersonation attacks, man-in-the-middle attacks, replay attacks, and information-leakage attacks. As a result, we believe the proposed framework achieves efficiency at reasonable computation and communication costs and it can be a safeguard to real heterogeneous WSN applications. PMID:24521942

  9. Mutualism Breakdown by Amplification of Wolbachia Genes

    PubMed Central

    Chrostek, Ewa; Teixeira, Luis

    2015-01-01

    Most insect species are associated with vertically transmitted endosymbionts. Because of the mode of transmission, the fitness of these symbionts is dependent on the fitness of the hosts. Therefore, these endosymbionts need to control their proliferation in order to minimize their cost for the host. The genetic bases and mechanisms of this regulation remain largely undetermined. The maternally inherited bacteria of the genus Wolbachia are the most common endosymbionts of insects, providing some of them with fitness benefits. In Drosophila melanogaster, Wolbachia wMelPop is a unique virulent variant that proliferates massively in the hosts and shortens their lifespan. The genetic bases of wMelPop virulence are unknown, and their identification would allow a better understanding of how Wolbachia levels are regulated. Here we show that amplification of a region containing eight Wolbachia genes, called Octomom, is responsible for wMelPop virulence. Using Drosophila lines selected for carrying Wolbachia with different Octomom copy numbers, we demonstrate that the number of Octomom copies determines Wolbachia titers and the strength of the lethal phenotype. Octomom amplification is unstable, and reversion of copy number to one reverts all the phenotypes. Our results provide a link between genotype and phenotype in Wolbachia and identify a genomic region regulating Wolbachia proliferation. We also prove that these bacteria can evolve rapidly. Rapid evolution by changes in gene copy number may be common in endosymbionts with a high number of mobile elements and other repeated regions. Understanding wMelPop pathogenicity and variability also allows researchers to better control and predict the outcome of releasing mosquitoes transinfected with this variant to block human vector-borne diseases. Our results show that transition from a mutualist to a pathogen may occur because of a single genomic change in the endosymbiont. This implies that there must be constant selection on

  10. Mutualism breakdown by amplification of Wolbachia genes.

    PubMed

    Chrostek, Ewa; Teixeira, Luis

    2015-02-01

    Most insect species are associated with vertically transmitted endosymbionts. Because of the mode of transmission, the fitness of these symbionts is dependent on the fitness of the hosts. Therefore, these endosymbionts need to control their proliferation in order to minimize their cost for the host. The genetic bases and mechanisms of this regulation remain largely undetermined. The maternally inherited bacteria of the genus Wolbachia are the most common endosymbionts of insects, providing some of them with fitness benefits. In Drosophila melanogaster, Wolbachia wMelPop is a unique virulent variant that proliferates massively in the hosts and shortens their lifespan. The genetic bases of wMelPop virulence are unknown, and their identification would allow a better understanding of how Wolbachia levels are regulated. Here we show that amplification of a region containing eight Wolbachia genes, called Octomom, is responsible for wMelPop virulence. Using Drosophila lines selected for carrying Wolbachia with different Octomom copy numbers, we demonstrate that the number of Octomom copies determines Wolbachia titers and the strength of the lethal phenotype. Octomom amplification is unstable, and reversion of copy number to one reverts all the phenotypes. Our results provide a link between genotype and phenotype in Wolbachia and identify a genomic region regulating Wolbachia proliferation. We also prove that these bacteria can evolve rapidly. Rapid evolution by changes in gene copy number may be common in endosymbionts with a high number of mobile elements and other repeated regions. Understanding wMelPop pathogenicity and variability also allows researchers to better control and predict the outcome of releasing mosquitoes transinfected with this variant to block human vector-borne diseases. Our results show that transition from a mutualist to a pathogen may occur because of a single genomic change in the endosymbiont. This implies that there must be constant selection on

  11. Control in mutualisms: combined implications of partner choice and bargaining roles.

    PubMed

    Golubski, Antonio J; Klausmeier, Christopher A

    2010-12-21

    When two species form a mutualistic association, the degree of control that each has over the interaction may be pivotal in determining the relative benefit each obtains. We incorporate the capacity for partner choice into a model of mutualism based on the exchange of goods and/or services, where one guild of mutualists plays the role of proposer (proposing a price at which the goods and/or services will be exchanged) and the other plays the role of responder (accepting or rejecting the deal). We show how the payoff structure in this scenario and other closely related ones correspond to the ultimatum and demand games of economics. In the model, there are both costs and benefits to a guild whose players have control over interactions. Control over interactions in the sense of being able to exercise partner choice can benefit a guild by selecting for mutualism in its partners, but is most effective in selecting against moderately exploitative partners, and so can give highly exploitative partners an advantage. This can generate dynamics similar to taxon cycles or those seen in models with competition-colonization tradeoffs, wherein increasingly more mutualistic partners (acting as superior competitors) are selected for up to a tipping point, at which highly exploitative strategies (akin to superior colonizers) gain an advantage. Control over interactions in the sense of being able to appropriate 'surplus' payoffs in each interaction, which is selected for within-guild and is equivalent to playing the role of responders, selects against high demands (and so for mutualism) in the guild with control. Combining the two mechanisms, a high degree of mutualism in both guilds and coexistence of more mutualistic and more exploitative strategies within each are both consistent with control over the interaction being highly skewed toward one side that does what is in its own short-term interests.

  12. Diet-responsive microRNAs are likely exogenous

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a recent report Title "et al". fostered miRNA-375 and miR-200c knock-out pups to wild-type dams and arrived at the conclusion that milk microRNAs are bioavailable in trace amounts at best and that postprandial concentrations of microRNAs are too low to elicit biological effects. Their take home m...

  13. Magnetic Ligation Method for Quantitative Detection of MicroRNAs

    PubMed Central

    Liong, Monty; Im, Hyungsoon; Majmudar, Maulik D.; Aguirre, Aaron D.; Sebas, Matthew; Lee, Hakho; Weissleder, Ralph

    2014-01-01

    A magnetic ligation method is utilized for the detection of microRNAs amongst a complex biological background without polymerase chain reaction or nucleotide modification. The sandwich probes assay can be adapted to analyze a panel of microRNAs associated with cardiovascular diseases in heart tissue samples. PMID:24532323

  14. MicroRNA Transcriptome Profiles During Swine Skeletal Muscle Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MicroRNA (miR) are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells,...

  15. Suppressive effect of microRNA-143 in retinoblastoma

    PubMed Central

    Wang, Li-Lun; Hu, Hai-Feng; Feng, Yan-Qin

    2016-01-01

    AIM To investigate microRNA-143 expression and effect on suppression of retinoblastoma (RB) cells. METHODS The expression of microRNA-143 was investigated and compared in normal human retina tissue samples and in RB cell lines of Y79 and Weri1. The microRNA-143 mimics were transfected into the RB cell lines separately, and its effect on RB cell lines was detected using reverse-transcription quantitative polymerase chain reaction and Western blotting methods. RESULTS The microRNA-143 expression was significantly suppressed in RB cell lines. Overexpression of microRNA-143 significantly lowered cell viability and invasion of the RB cell lines, and increased the number of apoptotic cells. Meanwhile, the Bax expression was up-regulated and much higher in the microRNA-143 mimics transfected group than that in the negative control and the microRNA-143 inhibitor groups. CONCLUSION MicroRNA-143 exhibits suppressive effects in RB. The current study provides the perspective of a potential therapeutic treatment for RB. PMID:27990360

  16. MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme.

    PubMed

    Li, Wen-Bo; Ma, Min-Wang; Dong, Li-Jie; Wang, Fei; Chen, Lu-Xia; Li, Xiao-Rong

    2011-09-15

    Aberrant expression of microRNAs (miRNAs) has been implicated in cancer initiation and progression. In this study, we found that microRNA-34a (miR-34a) is significantly downregulated in glioblastoma multiforme (GBM) specimens compared with normal brain tissues. Growth curve and colony formation assays revealed that miR-34a suppresses proliferation of U373MG and SHG44 glioblastoma cells. Overexpression of miR-34a could induce apoptosis of glioblastoma cells. Also, we identified notch1 as a direct target gene of miR-34a. Knockdown of notch1 showed similar cellular functions as overexpression of miR-34a both in vitro and in vivo. Collectively, our findings show that miR-34a is downregulated in GBM cells and inhibits GBM growth by targeting notch1.

  17. MicroRNA precursors are not structurally robust but plastic.

    PubMed

    Rodrigo, Guillermo; Elena, Santiago F

    2013-01-01

    Robustness is considered a ubiquitous property of living systems at all levels of organization, and small noncoding RNA (sncRNA) is a genuine model for its study at the molecular level. In this communication, we question whether microRNA precursors (pre-miRNAs) are actually structurally robust, as previously suggested. We found that natural pre-miRNAs are not more robust than expected under an appropriate null model. On the contrary, we found that eukaryotic pre-miRNAs show a significant enrichment in conformational flexibility at the thermal equilibrium of the molecule, that is, in their plasticity. Our results further support the selection for functional diversification and evolvability in sncRNAs.

  18. Circulating micrornas as potential biomarkers of muscle atrophy

    NASA Astrophysics Data System (ADS)

    Wang, Fei

    2016-07-01

    Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P < 0.01). And, the level of miR-1 and miR-23a were all elevated in the serum of hindlimb unloaded mice (P < 0.01). miR-23a levels were negatively correlated with both muscle mass and muscle fiber cross section area in muscle atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

  19. A microRNA code for prostate cancer metastasis

    PubMed Central

    Bonci, D; Coppola, V; Patrizii, M; Addario, A; Cannistraci, A; Francescangeli, F; Pecci, R; Muto, G; Collura, D; Bedini, R; Zeuner, A; Valtieri, M; Sentinelli, S; Benassi, M S; Gallucci, M; Carlini, P; Piccolo, S; De Maria, R

    2016-01-01

    Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment. PMID:26073083

  20. The Role of MicroRNAs in Diabetic Nephropathy

    PubMed Central

    Kong, Lili; Cui, Wenpeng; Li, Xiangqi; Tan, Yi; Miao, Lining

    2014-01-01

    Diabetic nephropathy (DN), as one of the chronic complications of diabetes, is the major cause of end-stage renal disease. However, the pathogenesis of this disease is not fully understood. In recent years, research on microRNAs (miRNAs) has become a hotspot because of their critical role in regulating posttranscriptional levels of protein-coding genes that may serve as key pathogenic factors in diseases. Several miRNAs were found to participate in the pathogenesis of DN, while others showed renal protective effects. Therefore, targeting miRNAs that are involved in DN may have a good prospect in the treatment of the disease. The aim of this review is to summarize DN-related miRNAs and provide potential targets for diagnostic strategies and therapeutic intervention. PMID:25258717

  1. Control of cell proliferation by microRNAs in plants.

    PubMed

    Rodriguez, Ramiro E; Schommer, Carla; Palatnik, Javier F

    2016-12-01

    Plants have the ability to generate different and new organs throughout their life cycle. Organ growth is mostly determined by the combinatory effects of cell proliferation and cell expansion. Still, organ size and shape are adjusted constantly by environmental conditions and developmental timing. The plasticity of plant development is further illustrated by the diverse organ forms found in nature. MicroRNAs (miRNAs) are known to control key biological processes in plants. In this review, we will discuss recent findings showing the participation of miRNA networks in the regulation of cell proliferation and organ growth. It has become clear that miRNA networks play both integrative and specific roles in the control of organ development in Arabidopsis thaliana. Furthermore, recent work in different species demonstrated a broad role for miR396 in the control of organ size, and that specific tuning of the miR396 network can improve crop yield.

  2. Expression of Serum microRNAs is Altered During Acute Graft-versus-Host Disease

    PubMed Central

    Crossland, Rachel E.; Norden, Jean; Juric, Mateja Kralj; Green, Kile; Pearce, Kim F.; Lendrem, Clare; Greinix, Hildegard T.; Dickinson, Anne M.

    2017-01-01

    Acute graft-versus-host disease (aGvHD) is the most frequent and serious complication following hematopoietic stem cell transplantation (HSCT), with a high mortality rate. A clearer understanding of the molecular pathogenesis may allow for improved therapeutic options or guide personalized prophylactic protocols. Circulating microRNAs are expressed in body fluids and have recently been associated with the etiology of aGvHD, but global expression profiling in a HSCT setting is lacking. This study profiled expression of n = 799 mature microRNAs in patient serum, using the NanoString platform, to identify microRNAs that showed altered expression at aGvHD diagnosis. Selected microRNAs (n = 10) were replicated in independent cohorts of serum samples taken at aGvHD diagnosis (n = 42) and prior to disease onset (day 14 post-HSCT, n = 47) to assess their prognostic potential. Sera from patients without aGvHD were used as controls. Differential microRNAs were investigated in silico for predicted networks and mRNA targets. Expression analysis identified 61 microRNAs that were differentially expressed at aGvHD diagnosis. miR-146a (p = 0.03), miR-30b-5p (p = 0.007), miR-374-5p (p = 0.02), miR-181a (p = 0.03), miR-20a (p = 0.03), and miR-15a (p = 0.03) were significantly verified in an independent cohort (n = 42). miR-146a (p = 0.01), miR-20a (p = 0.03), miR-18 (p = 0.03), miR-19a (p = 0.03), miR-19b (p = 0.01), and miR-451 (p = 0.01) were differentially expressed 14 days post-HSCT in patients who later developed aGvHD (n = 47). High miR-19b expression was associated with improved overall survival (OS) (p = 0.008), whereas high miR-20a and miR-30b-5p were associated with lower rates of non-relapse mortality (p = 0.05 and p = 0.008) and improved OS (p = 0.016 and p = 0.021). Pathway analysis associated the candidate microRNAs with hematological and inflammatory disease. Circulating

  3. Evolutionary origin of insect–Wolbachia nutritional mutualism

    PubMed Central

    Nikoh, Naruo; Hosokawa, Takahiro; Moriyama, Minoru; Oshima, Kenshiro; Hattori, Masahira; Fukatsu, Takema

    2014-01-01

    Obligate insect–bacterium nutritional mutualism is among the most sophisticated forms of symbiosis, wherein the host and the symbiont are integrated into a coherent biological entity and unable to survive without the partnership. Originally, however, such obligate symbiotic bacteria must have been derived from free-living bacteria. How highly specialized obligate mutualisms have arisen from less specialized associations is of interest. Here we address this evolutionary issue by focusing on an exceptional insect–Wolbachia nutritional mutualism. Although Wolbachia endosymbionts are ubiquitously found in diverse insects and generally regarded as facultative/parasitic associates for their insect hosts, a Wolbachia strain associated with the bedbug Cimex lectularius, designated as wCle, was shown to be essential for host’s growth and reproduction via provisioning of B vitamins. We determined the 1,250,060-bp genome of wCle, which was generally similar to the genomes of insect-associated facultative Wolbachia strains, except for the presence of an operon encoding the complete biotin synthetic pathway that was acquired via lateral gene transfer presumably from a coinfecting endosymbiont Cardinium or Rickettsia. Nutritional and physiological experiments, in which wCle-infected and wCle-cured bedbugs of the same genetic background were fed on B-vitamin–manipulated blood meals via an artificial feeding system, demonstrated that wCle certainly synthesizes biotin, and the wCle-provisioned biotin significantly contributes to the host fitness. These findings strongly suggest that acquisition of a single gene cluster consisting of biotin synthesis genes underlies the bedbug–Wolbachia nutritional mutualism, uncovering an evolutionary transition from facultative symbiosis to obligate mutualism facilitated by lateral gene transfer in an endosymbiont lineage. PMID:24982177

  4. Evolutionary origin of insect-Wolbachia nutritional mutualism.

    PubMed

    Nikoh, Naruo; Hosokawa, Takahiro; Moriyama, Minoru; Oshima, Kenshiro; Hattori, Masahira; Fukatsu, Takema

    2014-07-15

    Obligate insect-bacterium nutritional mutualism is among the most sophisticated forms of symbiosis, wherein the host and the symbiont are integrated into a coherent biological entity and unable to survive without the partnership. Originally, however, such obligate symbiotic bacteria must have been derived from free-living bacteria. How highly specialized obligate mutualisms have arisen from less specialized associations is of interest. Here we address this evolutionary issue by focusing on an exceptional insect-Wolbachia nutritional mutualism. Although Wolbachia endosymbionts are ubiquitously found in diverse insects and generally regarded as facultative/parasitic associates for their insect hosts, a Wolbachia strain associated with the bedbug Cimex lectularius, designated as wCle, was shown to be essential for host's growth and reproduction via provisioning of B vitamins. We determined the 1,250,060-bp genome of wCle, which was generally similar to the genomes of insect-associated facultative Wolbachia strains, except for the presence of an operon encoding the complete biotin synthetic pathway that was acquired via lateral gene transfer presumably from a coinfecting endosymbiont Cardinium or Rickettsia. Nutritional and physiological experiments, in which wCle-infected and wCle-cured bedbugs of the same genetic background were fed on B-vitamin-manipulated blood meals via an artificial feeding system, demonstrated that wCle certainly synthesizes biotin, and the wCle-provisioned biotin significantly contributes to the host fitness. These findings strongly suggest that acquisition of a single gene cluster consisting of biotin synthesis genes underlies the bedbug-Wolbachia nutritional mutualism, uncovering an evolutionary transition from facultative symbiosis to obligate mutualism facilitated by lateral gene transfer in an endosymbiont lineage.

  5. MicroRNAs control neurobehavioral development and function in zebrafish

    PubMed Central

    Tal, Tamara L.; Franzosa, Jill A.; Tilton, Susan C.; Philbrick, Kenneth A.; Iwaniec, Urszula T.; Turner, Russell T.; Waters, Katrina M.; Tanguay, Robert L.

    2012-01-01

    microRNAs (miRNAs) have emerged as regulators of a broad spectrum of neurodevelopmental processes, including brain morphogenesis, neuronal differentiation, and survival. While the role of miRNAs in establishing and maintaining the developing nervous system is widely appreciated, the developmental neurobehavioral role of miRNAs has yet to be defined. Here we show that transient disruption of brain morphogenesis by ethanol exposure results in behavioral hyperactivity in larval zebrafish challenged with changes in lighting conditions. Aberrations in swimming activity persist in juveniles that were developmentally exposed to ethanol. During early neurogenesis, multiple gene expression profiling studies revealed widespread changes in mRNA and miRNA abundance in ethanol-exposed embryos. Consistent with a role for miRNAs in neurobehavioral development, target prediction analyses identified multiple miRNAs misexpressed in the ethanol-exposed cohorts that were also predicted to target inversely expressed transcripts known to influence brain morphogenesis. In vivo knockdown of miR-9/9* or miR-153c persistently phenocopied the effect of ethanol on larval and juvenile swimming behavior. Structural analyses performed on adults showed that repression of miR-153c during development impacts craniofacial skeletal development. Together, these data support an integral role for miRNAs in the establishment of vertebrate neurobehavioral and skeletal systems.—Tal, T. L., Franzosa, J. A., Tilton, S. C., Philbrick, K. A., Iwaniec, U. T., Turner, R. T., Waters, K. M., Tanguay, R. L. MicroRNAs control neurobehavioral development and function in zebrafish. PMID:22253472

  6. Function of Klotho and is MicroRNA in Prostate Cancer and Aging

    DTIC Science & Technology

    2008-10-01

    completely absent in prostate cancer samples whereas all of non- cancer tissues investigated showed strong staining for this miRNA , suggesting that...CONTRACT NUMBER Function of Klotho and is MicroRNA in Prostate Cancer and Aging 5b. GRANT NUMBER W81XWH-07-1-0264 5c. PROGRAM ELEMENT NUMBER 6...ABSTRACT We have observed the expression of CD164, IGFR, and Klotho proteins in human prostate cancer tissue microarrays as determined by

  7. MicroRNA-7 Promotes Glycolysis to Protect against 1-Methyl-4-phenylpyridinium-induced Cell Death.

    PubMed

    Chaudhuri, Amrita Datta; Kabaria, Savan; Choi, Doo Chul; Mouradian, M Maral; Junn, Eunsung

    2015-05-08

    Parkinson disease is associated with decreased activity of the mitochondrial electron transport chain. This defect can be recapitulated in vitro by challenging dopaminergic cells with 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin that inhibits complex I of electron transport chain. Consequently, oxidative phosphorylation is blocked, and cells become dependent on glycolysis for ATP production. Therefore, increasing the rate of glycolysis might help cells to produce more ATP to meet their energy demands. In the present study, we show that microRNA-7, a non-coding RNA that protects dopaminergic neuronal cells against MPP(+)-induced cell death, promotes glycolysis in dopaminergic SH-SY5Y and differentiated human neural progenitor ReNcell VM cells, as evidenced by increased ATP production, glucose consumption, and lactic acid production. Through a series of experiments, we demonstrate that targeted repression of RelA by microRNA-7, as well as subsequent increase in the neuronal glucose transporter 3 (Glut3), underlies this glycolysis-promoting effect. Consistently, silencing Glut3 expression diminishes the protective effect of microRNA-7 against MPP(+). Further, microRNA-7 fails to prevent MPP(+)-induced cell death when SH-SY5Y cells are cultured in a low glucose medium, as well as when differentiated ReNcell VM cells or primary mouse neurons are treated with the hexokinase inhibitor, 2-deoxy-d-glucose, indicating that a functional glycolytic pathway is required for this protective effect. In conclusion, microRNA-7, by down-regulating RelA, augments Glut3 expression, promotes glycolysis, and subsequently prevents MPP(+)-induced cell death. This protective effect of microRNA-7 could be exploited to correct the defects in oxidative phosphorylation in Parkinson disease.

  8. Correlation between EGFR amplification and the expression of microRNA-200c in primary glioblastoma multiforme.

    PubMed

    Serna, Eva; Lopez-Gines, Concha; Monleon, Daniel; Muñoz-Hidalgo, Lisandra; Callaghan, Robert C; Gil-Benso, Rosario; Martinetto, Horacio; Gregori-Romero, Aurelia; Gonzalez-Darder, Jose; Cerda-Nicolas, Miguel

    2014-01-01

    Extensive infiltration of the surrounding healthy brain tissue is a critical feature in glioblastoma. Several miRNAs have been related to gliomagenesis, some of them related with the EGFR pathway. We have evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns, studied by fluorescence in situ hybridization in tissue microarrays, of 30 cases of primary glioblastoma multiforme, whose clinicopathological and immunohistochemical features have also been analyzed. MicroRNA-200c showed a very significant difference between tumors having or not EGFR amplification. This microRNA plays an important role in epithelial-mesenchymal transition, but its implication in the behavior of glioblastoma is largely unknown. With respect to EGFR status our cases were categorized into three groups: high level EGFR amplification, low level EGFR amplification, and no EGFR amplification. Our results showed that microRNA-200c and E-cadherin expression are down-regulated, while ZEB1 is up-regulated, when tumors showed a high level of EGFR amplification. Conversely, ZEB1 mRNA expression levels were significantly lower in the group of tumors without EGFR amplification. Tumors with a low level of EGFR amplification showed ZEB1 expression levels comparable to those detected in the group with a high level of amplification. In this study we provide what is to our knowledge the first report of association between microRNA-200c and EGFR amplification in glioblastomas.

  9. Comparative profiling of microRNAs in the winged and wingless English grain aphid, Sitobion avenae (F.) (Homoptera: Aphididae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    English green aphid, Sitobion avenae (F.), show a classic polyphenic wing dimorphism among isogenic adults that is an intriguing model for the study of morphological plasticity in response to the environment. Short non-coding microRNA (miRNA) molecules regulate gene expression by post-transcriptiona...

  10. 26 CFR 1.831-1 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, and...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... insurance companies not carrying on an insurance business within the United States, and all mutual marine...) Foreign insurance companies not carrying on an insurance business within the United States are not taxable... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Tax on insurance companies (other than life...

  11. 26 CFR 1.831-1 - Tax on insurance companies (other than life or mutual), mutual marine insurance companies, and...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... foreign insurance companies not carrying on an insurance business within the United States, and all mutual... Code. (d) Foreign insurance companies not carrying on an insurance business within the United States... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Tax on insurance companies (other than life...

  12. Regulation of cardiac microRNAs by serum response factor.

    PubMed

    Zhang, Xiaomin; Azhar, Gohar; Helms, Scott A; Wei, Jeanne Y

    2011-02-08

    Serum response factor (SRF) regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg) led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg) resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  13. MicroRNA Modulation in Obesity and Periodontitis

    PubMed Central

    Perri, R.; Nares, S.; Zhang, S.; Barros, S.P.; Offenbacher, S.

    2012-01-01

    The aim of this pilot investigation was to determine if microRNA expression differed in the presence or absence of obesity, comparing gingival biopsies obtained from patients with or without periodontal disease. Total RNA was extracted from gingival biopsy samples collected from 20 patients: 10 non-obese patients (BMI < 30 kg/m2) and 10 obese patients (BMI > 30 kg/m2), each group with 5 periodontally healthy sites and 5 chronic periodontitis sites. MicroRNA expression patterns were assessed with a quantitative microRNA PCR array to survey 88 candidate microRNA species. Four microRNA databases were used to identify potential relevant mRNA target genes of differentially expressed microRNAs. Two microRNA species (miR-18a, miR-30e) were up-regulated among obese individuals with a healthy periodontium. Two microRNA species (miR-30e, miR-106b) were up-regulated in non-obese individuals with periodontal disease. In the presence of periodontal disease and obesity, 9 of 11 listed microRNAs were significantly up-regulated (miR-15a, miR-18a, miR-22, miR-30d, miR-30e, miR-103, miR-106b, miR-130a, miR-142-3p, miR-185, and miR-210). Predicted targets include 69 different mRNAs from genes that comprise cytokines, chemokines, specific collagens, and regulators of glucose and lipid metabolism. The expression of specific microRNA species in obesity, which could also target and post-transcriptionally modulate cytokine mRNA, provides new insight into possible mechanisms of how risk factors might modify periodontal inflammation and may represent novel therapeutic targets. PMID:22043006

  14. MicroRNA in 2012: Biotherapeutic potential of microRNAs in rheumatic diseases.

    PubMed

    Pers, Yves-Marie; Jorgensen, Christian

    2013-02-01

    A number of microRNAs have been implicated in the pathogenesis of various rheumatic diseases, and evidence in support of the therapeutic potential of microRNA-based strategies for these conditions is growing, as demonstrated by several new findings published in 2012.

  15. Technology in MicroRNA Profiling: Circulating MicroRNAs as Noninvasive Cancer Biomarkers in Breast Cancer.

    PubMed

    Pimentel, Fernando; Bonilla, Patricia; Ravishankar, Yashwanth G; Contag, Alec; Gopal, Nimish; LaCour, Sarah; Lee, Trenton; Niemz, Angelika

    2015-10-01

    This report describes technologies to identify and quantify microRNAs (miRNAs) as potential cancer biomarkers, using breast cancer as an example. Most breast cancer patients are not diagnosed until the disease has advanced to later stages, which decreases overall survival rates. Specific miRNAs are up- or downregulated in breast cancer patients at various stages, can be detected in plasma and serum, and have shown promising preliminary clinical sensitivity and specificity for early cancer diagnosis or staging. Nucleic acid testing methods to determine relative concentrations of selected miRNAs include reverse transcription, followed by quantitative PCR (RT-qPCR), microarrays, and next-generation sequencing (NGS). Of these methods, NGS is the most powerful approach for miRNA biomarker discovery, whereas RT-qPCR shows the most promise for eventual clinical diagnostic applications.

  16. Synchronization in networks of mutually delay-coupled phase-locked loops

    NASA Astrophysics Data System (ADS)

    Pollakis, Alexandros; Wetzel, Lucas; Jörg, David J.; Rave, Wolfgang; Fettweis, Gerhard; Jülicher, Frank

    2014-11-01

    Electronic components that perform tasks in a concerted way rely on a common time reference. For instance, parallel computing demands synchronous clocking of multiple cores or processors to reliably carry out joint computations. Here, we show that mutually coupled phase-locked loops (PLLs) enable synchronous clocking in large-scale systems with transmission delays. We present a phase description of coupled PLLs that includes filter kernels and delayed signal transmission. We find that transmission delays in the coupling enable the existence of stable synchronized states, while instantaneously coupled PLLs do not tend to synchronize. We show how filtering and transmission delays govern the collective frequency and the time scale of synchronization.

  17. Urinary MicroRNA-30c-5p and MicroRNA-192-5p as potential biomarkers of ischemia-reperfusion-induced kidney injury.

    PubMed

    Zou, Yan-Fang; Wen, Dan; Zhao, Qian; Shen, Ping-Yan; Shi, Hao; Zhao, Qiang; Chen, Yong-Xi; Zhang, Wen

    2017-03-01

    Early detection of acute kidney injury is difficult due to lack of known biomarkers; previous studies have tried to identify new biomarkers for detecting acute kidney injury at an early stage. MicroRNA, a 21-23 nucleotide noncoding RNA molecule, has emerged as a desirable marker in the diagnosis and prognosis of various diseases. This study aims to identify the expression profile of microRNA in ischemia-reperfusion-induced kidney injury and determine the possibility of using the candidate microRNA as biomarker for the detection of I/R-induced kidney injury. Based on the established rat model of I/R-induced kidney injury, a microarray analysis of rat urine was performed at the beginning of operation (0 h) as well as 72 h post operation. To validate the results, urine samples from 71 patients who underwent cardiac surgery were collected, after which urinalysis was conducted to determine the microRNA concentration. An alternative expression profile of microRNAs was detected in rat urine. The quantitative validation of microRNA showed that the expression of miR-30c-5p, miR-192-5p, and miR-378a-3p was elevated significantly in urine post operation, which was consistent with those of the microarray analysis and earlier than kidney injury molecule-1 (KIM-1). In patients with acute kidney injury, increased levels of miR-30c-5p and miR-192-5p were also detected 2 h post operation, and miR-30c-5p showed preferable diagnostic value compared with protein-based biomarkers. In conclusion, an aberrant expression profile of microRNA was detected in rat urine based on the established ischemia-reperfusion animal model. Both miR-30c-5p and miR-192-5p served as important potential diagnostic markers for I/R-induced kidney injury. Impact statement Firstly, one differentiating factor in our study is that the candidate miRNAs were screened in a controlled animal model rather than in patients with acute kidney injury (AKI) to ensure the purity of the cause of disease and to avoid

  18. Pollination and seed predation by moths on Silene and allied Caryophyllaceae: evaluating a model system to study the evolution of mutualisms.

    PubMed

    Kephart, Susan; Reynolds, Richard J; Rutter, Matthew T; Fenster, Charles B; Dudash, Michele R

    2006-01-01

    Nursery pollinators, and the plants they use as hosts for offspring development, function as exemplary models of coevolutionary mutualism. The two pre-eminent examples--fig wasps and yucca moths--show little variation in the interaction: the primary pollinator is an obligate mutualist. By contrast, nursery pollination of certain Caryophyllaceae, including Silene spp., by two nocturnal moth genera, Hadena and Perizoma, ranges from antagonistic to potentially mutualistic, offering an opportunity to test hypotheses about the factors that promote or discourage the evolution of mutualism. Here, we review nursery pollination and host-plant interactions in over 30 caryophyllaceous plants, based on published studies and a survey of researchers investigating pollination, seed predation, and moth morphology and behavior. We detected little direct evidence of mutualism in these moth-plant interactions, but found traits and patterns in both that are nonetheless consistent with the evolution of mutualism and merit further attention.

  19. Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks

    PubMed Central

    McSweeney, K. Melodi; Gussow, Ayal B.; Bradrick, Shelton S.; Dugger, Sarah A.; Gelfman, Sahar; Wang, Quanli; Petrovski, Slavé; Frankel, Wayne N.; Boland, Michael J.; Goldstein, David B.

    2016-01-01

    Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons. These results support the utility of MEAs in developing in vitro models of neuroexcitability disorders, such as epilepsy, and further suggest that MEAs provide an effective tool for the rapid identification of microRNAs that promote seizures when dysregulated. PMID:27516621

  20. DNA damage modulates interactions between microRNAs and the 26S proteasome

    PubMed Central

    Tsimokha, Anna S; Kulichkova, Valentina A.; Karpova, Elena V.; Zaykova, Julia J.; Aksenov, Nikolai D; Vasilishina, Anastasia A.; Kropotov, Andrei V.; Antonov, Alexey; Barlev, Nikolai A.

    2014-01-01

    26S proteasomes are known as major non-lysosomal cellular machines for coordinated and specific destruction of ubiquitinylated proteins. The proteolytic activities of proteasomes are controlled by various post-translational modifications in response to environmental cues, including DNA damage. Besides proteolysis, proteasomes also associate with RNA hydrolysis and splicing. Here, we extend the functional diversity of proteasomes by showing that they also dynamically associate with microRNAs (miRNAs) both in the nucleus and cytoplasm of cells. Moreover, DNA damage induced by an anti-cancer drug, doxorubicin, alters the repertoire of proteasome-associated miRNAs, enriching the population of miRNAs that target cell cycle checkpoint regulators and DNA repair proteins. Collectively, these data uncover yet another potential mode of action for proteasomes in the cell via their dynamic association with microRNAs. PMID:25004448

  1. Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks.

    PubMed

    McSweeney, K Melodi; Gussow, Ayal B; Bradrick, Shelton S; Dugger, Sarah A; Gelfman, Sahar; Wang, Quanli; Petrovski, Slavé; Frankel, Wayne N; Boland, Michael J; Goldstein, David B

    2016-10-01

    Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons. These results support the utility of MEAs in developing in vitro models of neuroexcitability disorders, such as epilepsy, and further suggest that MEAs provide an effective tool for the rapid identification of microRNAs that promote seizures when dysregulated.

  2. Spatially weighted mutual information image registration for image guided radiation therapy

    SciTech Connect

    Park, Samuel B.; Rhee, Frank C.; Monroe, James I.; Sohn, Jason W.

    2010-09-15

    SWMI registration with a Gaussian weight function (SWMI-GW) was tested between two different imaging modalities: CT and MRI image sets. Results: SWMI-GW converges 10% faster than registration using mutual information with an ROI. SWMI-GW as well as SWMI with SOI-based weight function (SWMI-SOI) shows better compensation of the target organ's deformation and neighboring critical organs' deformation. SWMI-GW was also used to successfully fuse MRI and CT images. Conclusions: Rigid-body image registration using our SWMI-GW and SWMI-SOI as cost functions can achieve better registration results in (a) designated image region(s) as well as faster convergence. With the theoretical foundation established, we believe SWMI could be extended to larger clinical testing.

  3. Mutual Regioselective Inhibition of Human UGT1A1-Mediated Glucuronidation of Four Flavonoids

    PubMed Central

    Ma, Guo; Wu, Baojian; Gao, Song; Yang, Zhen; Ma, Yong; Hu, Ming

    2013-01-01

    UDP-glucuronosyltransferase (UGT) 1A1-catalyzed glucuronidation is an important elimination pathway of flavonoids, and mutually inhibitory interactions may occur when two or more flavonoids are co-administered. Our recent research suggested that glucuronidation of flavonoids displayed distinct positional preferences, but whether this will lead to the mutually regioselective inhibition of UGT1A1-mediated glucuronidation of flavonoids is unknown. Therefore, we chose three monohydroxyflavone isomers 3-hydroxyflavone (3HF), 7-hydroxyflavone (7HF), 4′-hydroxyflavone (4′HF) and one trihydroxyflavone 3,7,4′-trihydroxyflavone (3,7,4′THF) as the model compounds to characterize the possible mutually regioselective inhibition of glucuronidation using expressed human UGT1A1. Apparent kinetic parameters [e.g., reaction velocity (V), Michaelis-Menten constant (Km), maximum rate of metabolism (Vmax), concentration at which inhibitor achieve 50% inhibition or IC50] and the Lineweaver-Burk plots were used to evaluate the apparent kinetic mechanisms of inhibition of glucuronidation. The results showed that UGT1A1-mediated glucuronidation of three monohydroxyflavones (i.e., 3HF, 7HF and 4′HF) and 3,7,4′THF was mutually inhibitory, and the mechanisms of inhibition appeared to be the mixed-typed inhibition. Specifically, the inhibitory effects displayed certain positional preference. Glucuronidation of 3HF was more easily inhibited by 3,7,4′THF than that of 7HF or 4′HF. Compared to 7-O-glucuronidation of 3,7,4′THF, 3-O-glucuronidation of 3,7,4′THF was more inhibited by 3HF and 4′HF, whereas glucuronidation at both 3-OH and 7-OH positions of 3,7,4′THF was more easily inhibited by 7HF than by 3HF and 4′HF. In conclusion, 3HF, 7HF, 4′HF and 3,7,4′THF were both substrates and inhibitors of UGT1A1, and they exhibited mutually regioselective inhibition of UGT1A1-mediated glucuronidation via a mixed-type inhibitory mechanism. PMID:23786524

  4. MicroRNAs in renal fibrosis

    PubMed Central

    Chung, Arthur C.-K.; Lan, Hui Y.

    2015-01-01

    MicroRNAs (miRNAs) are endogenous short non-coding RNAs that regulate most of important cellular processes by inhibiting gene expression through the post-transcriptional repression of their target mRNAs. In kidneys, miRNAs have been associated in renal development, homeostasis, and physiological functions. Results from clinical and experimental animal studies demonstrate that miRNAs play essential roles in the pathogenesis of various renal diseases. Chronic kidney diseases (CKD) is characterized by renal fibrosis. Transforming growth factor beta (TGF-β) is recognized as a major mediator of renal fibrosis because it is able to stimulate the accumulation of extracellular matrix (ECM) proteins to impair normal kidney function. Recently, emerging evidence demonstrate the relationship between TGF-β signaling and miRNAs expression during renal diseases. TGF-β regulates expression of several microRNAs, such as miR-21, miR-192, miR-200, miR-433, and miR-29. MiR-21, miR-192, and miR-433 which are positively induced by TGF-β signaling play a pathological role in kidney diseases. In contrast, members in both miR-29 and miR-200 families which are inhibited by TGF-β signaling protect kidneys from renal fibrosis by suppressing the deposition of ECM and preventing epithelial-to-mesenchymal transition, respectively. Clinically, the presence of miRNAs in blood and urine has been examined to be early biomarkers for detecting renal diseases. From experimental animal studies of CKD, targeting microRNAs also provides evidence about therapeutic potential of miRNAs during renal diseases. Now, it comes to the stage to examine the exact mechanisms of miRNAs during the initiation and progression of renal diseases. Therefore, determining the function of miRNAs in renal fibrosis may facilitate the development of both early diagnosis and treatment of renal diseases. PMID:25750628

  5. microRNAs and Fragile X Syndrome.

    PubMed

    Lin, Shi-Lung

    2015-01-01

    Fragile X syndrome (FXS) is one of the major causes for autism and mental retardation in humans. The etiology of FXS is linked to the expansion of the CGG trinucleotide repeats, r(CGG), suppressing the fragile X mental retardation 1 (FMR1) gene on the X chromosome, resulting in a loss of fragile X mental retardation protein (FMRP) expression, which is required for regulating normal neuronal connectivity and plasticity. Recent studies have further identified that microRNAs are involved in the mechanisms underlying FXS pathogenesis at three different developmental stages. During early embryogenesis before the blastocyst stage, an embryonic stem cell (ESC)-specific microRNA, miR-302, interferes with FMR1 mRNA translation to maintain the stem cell status and inhibit neural development. After blastocyst, the downregulation of miR-302 releases FMRP synthesis and subsequently leads to neuronal development; yet, in FXS, certain r(CGG)-derived microRNAs, such as miR-fmr1s, are expressed and accumulated and then induce DNA hypermethylation on the FMR1 gene promoter regions, resulting in transcriptional inactivation of the FMR1 gene and the loss of FMRP. In normal neuronal development, FMRP is an RNA-binding protein responsible for interacting with miR-125 and miR-132 to regulate the signaling of Group 1 metabotropic glutamate receptor (mGluR1) and N-methyl-D-aspartate receptor (NMDAR), respectively, and consequently affecting synaptic plasticity. As a result, the loss of FMRP impairs these signaling controls and eventually causes FXS-associated disorders, such as autism and mental retardation. Based on these current findings, this chapter will summarize the etiological causes of FXS and further provides significant insights into the molecular mechanisms underlying microRNA-mediated FXS pathogenesis and the related therapy development.

  6. MicroRNA biogenesis pathways in cancer

    PubMed Central

    Lin, Shuibin; Gregory, Richard I.

    2016-01-01

    MicroRNAs (miRNAs) are critical regulators of gene expression. Amplification and overexpression of individual ‘oncomiRs’ or genetic loss of tumour suppressor miRNAs are associated with human cancer and are sufficient to drive tumorigenesis in mouse models. Furthermore, global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic. This, together with the recent identification of novel miRNA regulatory factors and pathways, highlights the importance of miRNA dysregulation in cancer. PMID:25998712

  7. A sense-able microRNA

    PubMed Central

    Pasquinelli, Amy E.

    2016-01-01

    In this issue of Genes & Development, Drexel and colleagues (pp. 2042–2047) present a beautiful example of how microRNAs (miRNAs) can regulate tissue-specific gene expression in a biologically relevant setting. They found that miR-791 is expressed in only three types of carbon dioxide (CO2)-sensing neurons in Caenorhabditis elegans, and its primary function there seems to be repression of two target genes that interfere with the behavioral response to CO2. Interestingly, these two targets are broadly expressed across other tissues. Thus, restricted miRNA expression can lead to target repression in select tissues to promote distinct cellular physiologies. PMID:27798846

  8. Identification of plant microRNA homologs.

    PubMed

    Dezulian, Tobias; Remmert, Michael; Palatnik, Javier F; Weigel, Detlef; Huson, Daniel H

    2006-02-01

    MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that regulate gene and protein expression in plants and animals. MiRNAs have so far been identified mostly by specific cloning of small RNA molecules, complemented by computational methods. We present a computational identification approach that is able to identify candidate miRNA homologs in any set of sequences, given a query miRNA. The approach is based on a sequence similarity search step followed by a set of structural filters.

  9. MicroRNAs in gastric cancer metastasis.

    PubMed

    Shi, Zhaoqi; Wei, Qingxia; She, Junjun

    2014-01-01

    Gastric cancer (GC) is common worldwide and has a high rate of metastasis. The underlying molecular mechanism of metastasis are not entirely clear. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally and are reported to be involved in multiple steps of tumor metastasis. Clarifying their roles in GC metastasis will improve understanding of this disease. Here, we review the involvement of miRNAs in multiple steps of GC metastasis, including epithelial-mesenchymal transitions, anoikis, angiogenesis, invasion, and migration. The clinical application of miRNAs as prognostic biomarkers in GC is also discussed.

  10. Block-circulant matrices with circulant blocks, Weil sums, and mutually unbiased bases. II. The prime power case

    SciTech Connect

    Combescure, Monique

    2009-03-15

    In our previous paper [Combescure, M., 'Circulant matrices, Gauss sums and the mutually unbiased bases. I. The prime number case', Cubo A Mathematical Journal (unpublished)] we have shown that the theory of circulant matrices allows to recover the result that there exists p+1 mutually unbiased bases in dimension p, p being an arbitrary prime number. Two orthonormal bases B, B{sup '} of C{sup d} are said mutually unbiased if for all b(set-membership sign)B, for all b{sup '}(set-membership sign)B{sup '} one has that |b{center_dot}b{sup '}|=1/{radical}(d) (b{center_dot}b{sup '} Hermitian scalar product in C{sup d}). In this paper we show that the theory of block-circulant matrices with circulant blocks allows to show very simply the known result that if d=p{sup n} (p a prime number and n any integer) there exists d+1 mutually unbiased bases in C{sup d}. Our result relies heavily on an idea of Klimov et al. [''Geometrical approach to the discrete Wigner function,'' J. Phys. A 39, 14471 (2006)]. As a subproduct we recover properties of quadratic Weil sums for p{>=}3, which generalizes the fact that in the prime case the quadratic Gauss sum properties follow from our results.

  11. Abiotic mediation of a mutualism drives herbivore abundance.

    PubMed

    Mooney, Emily H; Phillips, Joseph S; Tillberg, Chadwick V; Sandrow, Cheryl; Nelson, Annika S; Mooney, Kailen A

    2016-01-01

    Species abundance is typically determined by the abiotic environment, but the extent to which such effects occur through the mediation of biotic interactions, including mutualisms, is unknown. We explored how light environment (open meadow vs. shaded understory) mediates the abundance and ant tending of the aphid Aphis helianthi feeding on the herb Ligusticum porteri. Yearly surveys consistently found aphids to be more than 17-fold more abundant on open meadow plants than on shaded understory plants. Manipulations demonstrated that this abundance pattern was not due to the direct effects of light environment on aphid performance, or indirectly through host plant quality or the effects of predators. Instead, open meadows had higher ant abundance and per capita rates of aphid tending and, accordingly, ants increased aphid population growth in meadow but not understory environments. The abiotic environment thus drives the abundance of this herbivore exclusively through the mediation of a protection mutualism.

  12. Refining and Mutual Separation of Rare Earths Using Biomass Wastes

    NASA Astrophysics Data System (ADS)

    Inoue, Katsutoshi; Alam, Shafiq

    2013-10-01

    Two different types of adsorption gels were prepared from biomass wastes. The first gel was produced from astringent persimmon peel rich in persimmon tannin, a polyphenol compound, which was prepared by means of simple dehydration condensation reaction using concentrated sulfuric acid for crosslinking. This adsorption gel was intended to be employed for the removal of radioactive elements, uranium (U(VI)) and thorium (Th(IV)), from rare earths. The second gel was prepared from chitosan, a basic polysaccharide, produced from shells of crustaceans such as crabs, shrimps, prawns, and other biomass wastes generated in marine product industry, by immobilizing functional groups of complexanes such as ethylendiaminetetraacetic acid and diethylentriaminepentaacetic acid (DTPA). This gel was developed for the mutual separation of rare earths. Of the two adsorption gels evaluated, the DTPA immobilized chitosan exhibited the most effective mutual separation among light rare earths.

  13. Integrated semiconductor twin-microdisk laser under mutually optical injection

    SciTech Connect

    Zou, Ling-Xiu; Liu, Bo-Wen; Lv, Xiao-Meng; Yang, Yue-De; Xiao, Jin-Long; Huang, Yong-Zhen

    2015-05-11

    We experimentally study the characteristics of an integrated semiconductor twin-microdisk laser under mutually optical injection through a connected optical waveguide. Based on the lasing spectra, four-wave mixing, injection locking, and period-two oscillation states are observed due to the mutually optical injection by adjusting the injected currents applied to the two microdisks. The enhanced 3 dB bandwidth is realized for the microdisk laser at the injection locking state, and photonic microwave is obtained from the electrode of the microdisk laser under the period-two oscillation state. The plentifully dynamical states similar as semiconductor lasers subject to external optical injection are realized due to strong optical interaction between the two microdisks.

  14. Bias reduction in the estimation of mutual information.

    PubMed

    Zhu, Jie; Bellanger, Jean-Jacques; Shu, Huazhong; Yang, Chunfeng; Le Bouquin Jeannès, Régine

    2014-11-01

    This paper deals with the control of bias estimation when estimating mutual information from a nonparametric approach. We focus on continuously distributed random data and the estimators we developed are based on a nonparametric k-nearest-neighbor approach for arbitrary metrics. Using a multidimensional Taylor series expansion, a general relationship between the estimation error bias and the neighboring size for the plug-in entropy estimator is established without any assumption on the data for two different norms. The theoretical analysis based on the maximum norm developed coincides with the experimental results drawn from numerical tests made by Kraskov et al. [Phys. Rev. E 69, 066138 (2004)PLEEE81539-375510.1103/PhysRevE.69.066138]. To further validate the novel relation, a weighted linear combination of distinct mutual information estimators is proposed and, using simulated signals, the comparison of different strategies allows for corroborating the theoretical analysis.

  15. Bias reduction in the estimation of mutual information

    NASA Astrophysics Data System (ADS)

    Zhu, Jie; Bellanger, Jean-Jacques; Shu, Huazhong; Yang, Chunfeng; Le Bouquin Jeannès, Régine

    2014-11-01

    This paper deals with the control of bias estimation when estimating mutual information from a nonparametric approach. We focus on continuously distributed random data and the estimators we developed are based on a nonparametric k -nearest-neighbor approach for arbitrary metrics. Using a multidimensional Taylor series expansion, a general relationship between the estimation error bias and the neighboring size for the plug-in entropy estimator is established without any assumption on the data for two different norms. The theoretical analysis based on the maximum norm developed coincides with the experimental results drawn from numerical tests made by Kraskov et al. [Phys. Rev. E 69, 066138 (2004), 10.1103/PhysRevE.69.066138]. To further validate the novel relation, a weighted linear combination of distinct mutual information estimators is proposed and, using simulated signals, the comparison of different strategies allows for corroborating the theoretical analysis.

  16. Role of mutual punishment in the snowdrift game

    NASA Astrophysics Data System (ADS)

    Yang, Han-Xin; Wang, Zhen

    2015-09-01

    The effects of punishment on cooperation have drawn increasing attention. In this paper, we propose a new mechanism of punishment, in which an individual will punish each neighbor if their strategies are different, and vice versa. We incorporate the mutual punishment into the snowdrift game. Results for well-mixed and structured populations have shown that, for no punishment or small values of punishment fine, the fraction of cooperators continuously decreases with the temptation to defect. However, for large values of punishment fine, there exists an abrupt transition point, at which the fraction of cooperators suddenly drops from 1 to 0. Compared to no punishment, mutual punishment promotes cooperation when the temptation to defect is small but inhibits cooperation when the temptation to defect is large. For weak (strong) temptation to defect, the cooperation level increases (decreases) with the punishment fine. For moderate temptation to defect, there exists an optimal value of the punishment fine that leads to the highest cooperation level.

  17. Kepler-108: A Mutually Inclined Giant Planet System

    NASA Astrophysics Data System (ADS)

    Mills, Sean M.; Fabrycky, Daniel C.

    2017-01-01

    The vast majority of well studied giant-planet systems, including the solar system, are nearly coplanar, which implies dissipation within a primordial gas disk. However, intrinsic instability may lead to planet–planet scattering, which often produces non-coplanar, eccentric orbits. Planet scattering theories have been developed to explain observed high-eccentricity systems and also hot Jupiters; thus far their predictions for mutual inclination (I) have barely been tested. Here we characterize a highly mutually inclined (I={24}-8+11°), moderately eccentric (e≳ 0.1) giant planet system: Kepler-108. This system consists of two approximately Saturn-mass planets with periods of approximately 49 and 190 days around a star with a wide (∼300 au) binary companion in an orbital configuration inconsistent with a purely disk migration origin.

  18. Circumstances for Pluto-Charon mutual events in 1987

    NASA Technical Reports Server (NTRS)

    Tholen, David J.; Buie, Marc W.; Swift, Catherine E.

    1987-01-01

    Circumstances are tabulated for 88 Pluto-Charon mutual events occurring during the 1987 opposition. Charon is predicted to be completely obscured either by Pluto or Pluto's shadow during each passage behind Pluto during this opposition, providing several opportunities to study Pluto uncontaminated by the light of Charon. The duration of these total events is predicted to be from 32 to 79 min. The mutual-event season is now expected to conclude during the 1990 opposition. Two new stars have been selected as comparison stars for events occurring prior to opposition in 1987. Standardization of the primary comparison stars used in 1985 and 1986 has yielded the following magnitudes: B = 12.6044 + or - 0.0015 and V = 11.7956 + or - 0.0017 (1985 Primary); B = 13.1238 + or 0.0008 and V = 12.3885 + or - 0.0014 (1986 Primary).

  19. Onset of fights and mutual assessment in ant founding queens.

    PubMed

    Berthelot, Kévin; Portugal, Felipe Ramon; Jeanson, Raphaël

    2017-03-01

    In animals, the progress and outcome of contests can be influenced by an individual's own condition, their opponent's condition or a combination of the two. The use of chemical information to assess the quality of rivals has been underestimated despite its central role in the regulation of social interactions in many taxa. Here, we studied pairwise contests between founding queens of the ant Lasius niger to investigate whether the decision to engage in agonistic interactions relies on self-assessment or mutual assessment. Queens modulated their aggressive behaviours depending on both their own status and their opponent's status. We found no influence of lipid stores or size on the onset of fights. However, differences in cuticular chemical signatures linked to fertility status accurately predicted the probability of behaving aggressively in pairs. Our study thus suggests that ant queens could rely on mutual assessment via chemical cues to make informed decisions about fight initiation.

  20. Improving quantum state estimation with mutually unbiased bases.

    PubMed

    Adamson, R B A; Steinberg, A M

    2010-07-16

    When used in quantum state estimation, projections onto mutually unbiased bases have the ability to maximize information extraction per measurement and to minimize redundancy. We present the first experimental demonstration of quantum state tomography of two-qubit polarization states to take advantage of mutually unbiased bases. We demonstrate improved state estimation as compared to standard measurement strategies and discuss how this can be understood from the structure of the measurements we use. We experimentally compared our method to the standard state estimation method for three different states and observe that the infidelity was up to 1.84 ± 0.06 times lower by using our technique than it was by using standard state estimation methods.