Edited by Tamas DalmayKeywords: MicroRNA Cardiomyocyte Proliferation Microarray MicroRNA-29a a b s t r a c t Recent studies demonstrated that the mammalian heart possesses some capacity to proliferate. We observed cardiomyocyte proliferation within 4 weeks of age (P4W) in rats. We found 95 microRNAs that are differentially expressed in P4W cardiomyocytes. MicroRNA-29a was among the most highly up-regulated microRNAs in P4W cardiomyocytes. Overexpression of microRNA-29a suppressed the proliferation of H9c2 cell line. MicroRNA-29a inhibition induced cardiomyocytes to proliferate, accelerated the G1/S and G2/M transition, and up-regulated the cell cycle gene expression. Cyclin D2 (CCND2) was identified as a direct target of microRNA-29a. These findings indicate that microR-NA-29a is involved in cardiomyocyte proliferation during postnatal development. Crown

Sensory neuron membrane proteins (SNMPs), which are located on the dendritic membrane of olfactory neurons, were considered as important components involved in pheromone reception in insects. In Drosophila melanogaster, mutants without SNMP are unable to evoke neuronal activities in the presence of pheromone cis-vaccenyl acetate (cVA). So deeply understanding the SNMPs functions may help to develop pheromone-mediated insect pest management tactics. The present study reports the identification and characterization of CmedSNMP1 and CmedSNMP2, two candidate SNMPs in the rice leaffolder, Cnaphalocrocis medinalis, one of the serious rice insect pests in Asia. The comparison of amino acid sequences shows that CmedSNMP1 and CmedSNMP2 are very similar to the previously reported SNMPs isolated from moths such as Ostrinia nubilalis and O. furnacalis, respectively, but the two CmedSNMPs share low identity with each other. The distribution patterns of two CmedSNMPs in different tissues of adult moths were examined using RT-PCR and quantitative real-time PCR. Although the two genes are expressed not only in antennae but also in nonolfactory tissues such as wings, legs, and body; the relative transcription level shows both CmedSNMP1 and CmedSNMP2 are highly enriched in antennae. The dN/dS ratios of the two CmedSNMPs indicate that the two genes are all subject to purifying selection and evolved to be functional genes. This work presents for the first time a study on the SNMPs of C. medinalis, which may help in providing guidance to future functional research of moth SNMPs.

Pim-2 is a serine/threonine protein kinase that is highly expressed in various types of cancer, with essential roles in the regulation of signal transduction cascades, which promote cell survival and proliferation. The present study demonstrated that Pim-2 was expressed in cells lines derived from hematopoietic tumors and lung cancer. In vitro, downregulation of Pim-2 by short interfering RNA inhibited proliferation and delayed G0/G1 cell cycle progression in K562 leukemia, RPMI-8226 multiple myeloma, and H1299 and A549 non-small cell lung carcinoma cell lines. Furthermore, downregulation of Pim-2 resulted in upregulation of cyclin-dependent kinase (CDK) inhibitor p21, irrespective of the p53 status. In addition, the present study revealed that CDK2 and phosphorylated retinoblastoma (pRb) were significantly downregulated. This finding suggested that inhibition of CDK2 and pRb expression via upregulated p21 was involved in the downregulation of Pim-2-induced G0/G1 cell cycle arrest in lung cancer and hematopoietic malignancy cells. These results suggested that Pim-2 may serve a role in hematopoietic tumors, lung cancer proliferation and cell cycle progression by regulating the p21 signaling pathway. Downregulation of Pim-2 decreased cancer cell proliferation. Therefore, Pim-2 may be a potential therapy target in clinical cancer therapy.

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The dynamic process of spermatogenesis shows little variation between invertebrate models such as Drosophila, and vertebrate models such as mice and rats. In each case, germ stem cells undergo mitotic division to proliferate and then continue, via meiosis, through various stages of elongation and individualization from spermatogonia to spermatid to finally to form mature sperm. Mature sperm are then stored in the seminal vesicles for fertilization. Errors in any of these stages can lead to male infertility. Here, we identify that Drosophila Pif1A acts as a key regulator for sperm individualization. Loss of Pif1A leads to male sterility associated with irregular individualization complex and empty seminal vesicles without mature sperm. Pif1A is highly expressed in the testes of mated male adult flies and the Pif1A protein is expressed at a higher level in male than in female flies. Pif1A is homologous to mammalian coiled-coil domain-containing protein 157 (CCDC157), which is also enriched in the testes of humans and mice. Human CCDC157, with unknown function, was identified to be downregulated in men with idiopathic non-obstructive azoospermia (NOA). We map the function of Drosophila Pif1A during spermatogenesis, showing that Pif1A is essential for spermatide individualization and involved in the regulation of the lipid metabolism genes. Our findings might be applicable for studying the function of CCDC157 in spermatogenesis and other aspects of human male fertility.

Most living organisms have developed internal circadian clocks to anticipate the daily environmental changes. The circadian clocks are composed of several transcriptional-translational feedback loops, in which cryptochromes (CRYs) serve as critical elements. In insects, some CRYs act as photopigments to control circadian photoentrainment, while the others act as transcriptional regulators. We cloned and characterized two cryptochrome genes, the Drosophila-like (lscry1) and vertebrate-like (lscry2) genes, in a rice pest Laodelphax striatellus. Quantitative real-time PCR showed that lscry1 and lscry2 expressed ubiquitously from nymph to adult stages as well as in different tissues. The transcript levels of lscry2 fluctuated in a circadian manner. Constant light led to arrhythmic locomotor activities in L. striatellus. It also inhibited the mRNA oscillation of lscry2 and promoted the transcription of lscry1. Knockdown of lscry1 or lscry2 by RNA interference (RNAi) reduced the rhythmicity of L. striatellus in constant darkness, but not in light dark cycles. These results suggested that lscry1 and lscry2 were putative circadian clock genes of L. striatellus, involved in the regulation of locomotor rhythms.

Summary Neuroprotection is essential for the maintenance of normal physiological functions in the nervous system. This is especially true under stress conditions. Here, we demonstrate a novel protective function of PRL-1 against CO 2 stimulation in Drosophila. In the absence of PRL-1, flies exhibit a permanent held-up wing phenotype upon CO 2 exposure. Knockdown of the CO 2 olfactory receptor, Gr21a, suppresses the phenotype. Our genetic data indicate that the wing phenotype is due to a neural dysfunction. PRL-1 physically interacts with Uex and controls Uex expression levels. Knockdown of Uex alone leads to a similar wing held-up phenotype to that of PRL-1 mutants. Uex acts downstream of PRL-1. Elevated Uex levels in PRL-1 mutants prevent the CO 2 -induced phenotype. PRL-1 and Uex are required for a wide range of neurons to maintain neuroprotective functions. Expression of human homologs of PRL-1 could rescue the phenotype in Drosophila , suggesting a similar function in humans.

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