A catalog of stability-associated sequence elements in 3' UTRs of yeast mRNAs

BACKGROUND: In recent years, intensive computational efforts have been directed towards the discovery of promoter motifs that correlate with mRNA expression profiles. Nevertheless, it is still not always possible to predict steady-state mRNA expression levels based on promoter signals alone, suggesting that other factors may be involved. Other genic regions, in particular 3' UTRs, which are known to exert regulatory effects especially through controlling RNA stability and localization, were less comprehensively investigated, and deciphering regulatory motifs within them is thus crucial. RESULTS: By analyzing 3' UTR sequences and mRNA decay profiles of Saccharomyces cerevisiae genes, we derived a catalog of 53 sequence motifs that may be implicated in stabilization or destabilization of mRNAs. Some of the motifs correspond to known RNA-binding protein sites, and one of them may act in destabilization of ribosome biogenesis genes during stress response. In addition, we present for the first time a catalog of 23 motifs associated with subcellular localization. A significant proportion of the 3' UTR motifs is highly conserved in orthologous yeast genes, and some of the motifs are strikingly similar to recently published mammalian 3' UTR motifs. We classified all genes into those regulated only at transcription initiation level, only at degradation level, and those regulated by a combination of both. Interestingly, different biological functionalities and expression patterns correspond to such classification. CONCLUSION: The present motif catalogs are a first step towards the understanding of the regulation of mRNA degradation and subcellular localization, two important processes which - together with transcription regulation - determine the cell transcriptome

Adsorption of fatty acid and fuel oil on iron-titanium minerals

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Effects of Waveform PMF on Anti-Spoofing Detection

International audienceIn the context of detection of speaker recognition identity impersonation , we observed that the waveform probability mass function (PMF) of genuine speech differs from significantly of of PMF from identity theft extracts. This is true for synthesized or converted speech as well as for replayed speech. In this work, we mainly ask whether this observation has a significant impact on spoofing detection performance. In a second step, we want to reduce the distribution gap of waveforms between authentic speech and spoofing speech. We propose a genuiniza-tion of the spoofing speech (by analogy with Gaussianisation), i.e. to obtain spoofing speech with a PMF close to the PMF of genuine speech. Our genuinization is evaluated on ASVspoof 2019 challenge datasets, using the baseline system provided by the challenge organization. In the case of constant Q cep-stral coefficients (CQCC) features, the genuinization leads to a degradation of the baseline system performance by a factor of 10, which shows a potentially large impact of the distribution os waveforms on spoofing detection performance. However, by ''playing" with all configurations, we also observed different behaviors, including performance improvements in specific cases. This leads us to conclude that waveform distribution plays an important role and must be taken into account by anti-spoofing systems

Time-Domain Based Embeddings for Spoofed Audio Representation

Anti-spoofing is the task of speech authentication. That is, identifying genuine human speech compared to spoofed speech. The main focus of this paper is to suggest new representations for genuine and spoofed speech, based on the probability mass function (PMF) estimation of the audio waveforms' amplitude. We introduce a new feature extraction method for speech audio signals: unlike traditional methods, our method is based on direct processing of time-domain audio samples. The PMF is utilized by designing a feature extractor based on different PMF distances and similarity measures. As an additional step, we used filter-bank preprocessing, which significantly affects the discriminative characteristics of the features and facilitates convenient visualization of possible clustering of spoofing attacks. Furthermore, we use diffusion maps to reveal the underlying manifold on which the data lies. The suggested embeddings allow the use of simple linear separators to achieve decent performance. In addition, we present a convenient way to visualize the data, which helps to assess the efficiency of different spoofing techniques. The experimental results show the potential of using multi-channel PMF based features for the anti-spoofing task, in addition to the benefits of using diffusion maps both as an analysis tool and as an embedding tool

Tetrahydropyrimidine derivatives inhibit binding of a Tat-like, arginine-containing peptide, to HIV TAR RNA in vitro

AbstractThe ability of a small molecule, 2-methyl,4-carboxy,5-hydroxy-3,4,5,6-tetrahydropyrimidine (THP(A)), which accumulates intracellularly in various streptomyces, to inhibit the interaction of Tat peptide (R52) with TAR RNA is presented. Using gel-shift assay, we found that the inhibition constant Ki of THP(A) is 50–100 nM, which is in the range of the binding constants of Tat peptide and protein. THP(A) is ∼ 106 times more tightly bound than the free l-arginine. The high binding affinity may be attributed to the special delocalized positive charge on the NCN group and the hydroxyl group at the 5 position of this molecule. A model for THP(A)-TAR interaction, analogous to the arginine guanidinum group-TAR interaction, is presented. The relatively high uptake of THP(A) by mammalian cells warrants in vivo Tat/TAR inhibition studies

Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3′,5′-cyclic diguanylic acid

AbstractThe effect of the novel, naturally occurring nucleotide cyclic diguanylic acid (c-di-GMP) on the lymphoblastoid CD4+ Jurkat cell line was studied. When exposed to 50 μM c-di-GMP, Jurkat cells exhibited a markedly elevated expression of the CD4 receptor of up to 6.3-fold over controls. C-di-GMP also causes blockage of the cell cycle at the S-phase, characterized by increased cellular thymidine uptake, reduction in G2/M-phase cells, increase in S-phase cells and decreased cell division. Additionally c-di-GMP naturally enters these cells and binds irreversibly to the P21ras protein. The effects described appear to be unique for c-di-GMP

Self-Organizing-Maps With BIC For Speaker Clustering

A new approach is presented for clustering the speakers from unlabeled and unsegmented conversation, when the number of speakers is unknown. In this approach, each speaker is modeled by a Self- Organizing-Map (SOM). For estimation of the number of clusters the Bayesian Information Criterion (BIC) is applied. This approach was tested on the NIST 1996 HUB-4 evaluation test in terms of speaker and cluster purities. Results indicate that the combined SOM-BIC approach can lead to better clustering results than the baseline system