MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3'-untranslated regions of target mRNAs. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and oncogenesis. Of more than 300 miRNAs that have been identified, miR-1 and miR-133 are considered to be muscle specific. Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. miR-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing KCNJ2 (which encodes the K(+) channel subunit Kir2.1) and GJA1 (which encodes connexin 43), and this likely accounts at least in part for its arrhythmogenic potential. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.

Natural language sentence matching is a fundamental technology for a variety of tasks. Previous approaches either match sentences from a single direction or only apply single granular (wordby-word or sentence-by-sentence) matching. In this work, we propose a bilateral multi-perspective matching (BiMPM) model. Given two sentences P and Q, our model first encodes them with a BiL-STM encoder. Next, we match the two encoded sentences in two directions P against Q and Q against P . In each matching direction, each time step of one sentence is matched against all timesteps of the other sentence from multiple perspectives. Then, another BiLSTM layer is utilized to aggregate the matching results into a fixed-length matching vector. Finally, based on the matching vector, a decision is made through a fully connected layer. We evaluate our model on three tasks: paraphrase identification, natural language inference and answer sentence selection. Experimental results on standard benchmark datasets show that our model achieves the state-of-the-art performance on all tasks.

Background-A characteristic of both clinical and experimental atrial fibrillation (AF) is atrial electric remodeling associated with profound reduction of L-type Ca 2ϩ current and shortening of the action potential duration. The possibility that microRNAs (miRNAs) may be involved in this process has not been tested. Accordingly, we assessed the potential role of miRNAs in regulating experimental AF. Methods and Results-The miRNA transcriptome was analyzed by microarray and verified by real-time reversetranscription polymerase chain reaction with left atrial samples from dogs with AF established by right atrial tachypacing for 8 weeks and from human atrial samples from AF patients with rheumatic heart disease. miR-223, miR-328, and miR-664 were found to be upregulated by Ͼ2 fold, whereas miR-101, miR-320, and miR-499 were downregulated by at least 50%. In particular, miR-328 level was elevated by 3.9-fold in AF dogs and 3.5-fold in AF patients relative to non-AF subjects. Computational prediction identified CACNA1C and CACNB1, which encode cardiac L-type Ca 2ϩ channel ␣1c-and ␤1 subunits, respectively, as potential targets for miR-328. Forced expression of miR-328 through adenovirus infection in canine atrium and transgenic approach in mice recapitulated the phenotypes of AF, exemplified by enhanced AF vulnerability, diminished L-type Ca 2ϩ current, and shortened atrial action potential duration. Normalization of miR-328 level with antagomiR reversed the conditions, and genetic knockdown of endogenous miR-328 dampened AF vulnerability. CACNA1C and CACNB1 as the cognate target genes for miR-328 were confirmed by Western blot and luciferase activity assay showing the reciprocal relationship between the levels of miR-328 and L-type Ca 2ϩ channel protein subunits. Conclusions-miR-328 contributes to the adverse atrial electric remodeling in AF through targeting L-type Ca 2ϩ channel genes. The study therefore uncovered a novel molecular mechanism for AF and indicated miR-328 as a potential therapeutic target for AF. (Circulation. 2010;122:2378-2387.)