Expression profile of microRNAs in young stroke patients

10.1371/journal.pone.0007689PLoS ONE41

Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients

The technology available for cancer diagnosis and prognosis is not yet satisfactory at the molecular level, and requires further improvements. Micro RNAs (miRNAs) have been recently reported as useful biomarkers in diseases including cancer. We performed a miRNA expression profiling study using peripheral blood from breast cancer patients to detect and identify characteristic patterns. A total of 100 breast cancer patients and 89 healthy patients were recruited for miRNA genotyping and expression profiling. We found that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs-miR-196a2 in postmenopausal patients, may discriminate breast cancer patients from healthy individuals. In addition, we found a significant association between two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk. However, no significant association between the hs-miR-146a gene and breast cancer risk was found. In summary, the study demonstrates that peripheral blood miRNAs and their expression and genotypic profiles can be developed as biomarkers for early diagnosis and prognosis of breast cancer

Drosophila Pur-α binds to trinucleotide-repeat containing cellular RNAs and translocates to the early oocyte.

Pur-alpha was identified as a DNA-binding protein with high affinity for the single-stranded PUR-motif (GGN)(n). Bound to DNA, Pur-alpha can both activate and repress transcription. In addition, Pur-alpha binds to RNA and may participate in nuclear RNA export as well as transport of cytoplasmic neuronal mRNP granules. The heritable trinucleotide-repeat expansion disease fragile X associated tremor and ataxia syndrome (FXTAS) leads to interaction of Pur-alpha with mutant, abnormally long r(CGG)(n) stretches, which appears to titrate the protein away from its physiologic mRNA targets into nuclear RNA-protein aggregates. We examined the function of Drosophila Pur-alpha and demonstrate that the protein accumulates in the growing oocyte early in oogenesis. Co-purifying proteins reveal that Pur-alpha is part of transported mRNP complexes, analogous to its reported role in nerve cells. We analyzed the subcellular localization of mutant GFP-Pur-alpha fusion proteins where either nucleic acid binding or dimerization, or both, were prevented. We propose that association with mRNAs occurs in the nucleus and is required for nuclear export of the complex. Furthermore, efficient translocation into the oocyte also requires RNA binding as well as dimerization. RNA binding assays demonstrate that recombinant Drosophila Pur-alpha can bind r(CGG)(4) with higher affinity than previously thought. Related sequences, such as r(CAG)(4) and the consensus sequence of the opa-repeat r(CAG)(3) CAA, can also associate with Pur-alpha in vitro and in vivo. The mRNA target spectrum of Pur-alpha may therefore be larger than previously anticipated

WNT/β-catenin signaling induces interleukin 1β expression by alveolar epithelial cells in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of yet unknown etiology. It is characterised by alterations of the alveolar epithelium, myofibroblast activation, and increased extracellular matrix deposition. Recently, reactivation of WNT/β-catenin signaling has been linked with IPF. The cell-specific mechanisms and mediators of WNT/β-catenin signaling in the lung, however, remain elusive. Here, we applied an unbiased gene expression screen to identify epithelial cell-specific mediators of WNT/β-catenin signaling. We found the proinflammatory cytokine interleukin (IL) 1β as one of the most upregulated genes in primary murine alveolar epithelial type (AT) II cells after WNT3a treatment. Increased transcript and protein expression of IL-1β upon WNT3a treatment was further detected in primary ATII cells by qRT-PCR (log-fold change: 2.0 +/- 0.5) and ELISA (1.8 fold increase). We observed significant IL-1β and IL-6 upregulation in bronchoalveolar lavage fluid (BALF) in bleomycin induced lung fibrosis in vivo. Importantly, primary fibrotic ATII cells secreted enhanced IL-1β and IL-6 in vitro. Furthermore, orotracheal application of recombinant WNT protein in TOPGAL reporter animals led to WNT/β-catenin activation in epithelial cells along with a significant increase in IL-1β and IL-6 in vivo (2.7-fold and 6.0-fold, respectively). Finally, we found increased WNT3a protein in fibrotic alveolar epithelium accompanied by enhanced IL-1β and IL-6 level in BALF from IPF patients. Taken together, our findings revealed that the alveolar epithelium is a relevant source of proinflammatory cytokines induced by active WNT/β-catenin. Thus, WNT/interleukin signaling represents a novel link between developmental pathway reactivation and inflammation in the development of pulmonary fibrosis

Electrostatic Self-Assembly of Protein Cage Arrays

Protein and peptide cages are nanoscale containers, which are of particular interest in nanoscience due to their well-defined dimensions and enclosed central cavities that can be filled with material that is protected from the outside environment. Ferritin is a typical example of protein cage, formed by 24 polypeptide chains that self-assemble into a hollow, roughly spherical protein cage with external and internal diameters of approximately 12 nm and 8 nm, respectively. The interior cavity of ferritin provides a unique reaction vessel to carry out reactions separated from the exterior environment. In nature, the cavity is utilized for sequestration and biomineralization to render iron inert and safe by shielding from the external environment. Materials scientists have been inspired by this system and exploited a range of ferritin superfamily proteins as supramolecular templates to encapsulate cargoes ranging from cancer drugs to therapeutic proteins. Interesting possibilities arise if such containers can themselves be arranged into even higher-order structures such as crystalline arrays. Here, we describe how crystalline arrays of negatively charged ferritin protein cages can be built by taking advantage of electrostatic interactions with cationic gold nanoparticles.Peer reviewe