The complete Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) genome contained 139,342 bp with a G+C content of 42.7%, and 141 putative open reading frames (ORFs) or genes of 150 nucleotides or greater that showed minimal overlap. Ninety-six ORFs had homologues in Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), 16 had homologues in other baculoviruses, and 29 were unique to SpltMNPV. The homologues of ubiquitin and gp37 are fused in SpltMNPV. The genome lacked a homologue of the major budded virus glycoprotein gene gp64, but it contained a homologue of ORF130 of Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV). There were two homologues of AcMNPV ORF2 (bro gene), and a DnaJ protein gene (SpltORF39) in which the N-terminus showed homologies with the J domain of DnaJ family proteins. Seventeen homologous regions (hrs) were identified, each containing 2-29 palindromic repeats, with an average length of 534 bp and base content (G+C%) of 33.0.
It is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex-forming capacity promote exon inclusion. Destroying G-quadruplex-forming capacity while keeping G tracts intact abrogates exon inclusion. Analysis of RNA-binding protein footprints revealed that G quadruplexes are enriched in heterogeneous nuclear ribonucleoprotein F (hnRNPF)-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome. Moreover, hnRNPF regulates an epithelial-mesenchymal transition (EMT)-associated CD44 isoform switch in a G-quadruplex-dependent manner, which results in inhibition of EMT. Mining breast cancer TCGA (The Cancer Genome Atlas) data sets, we demonstrate that hnRNPF negatively correlates with an EMT gene signature and positively correlates with patient survival. These data suggest a critical role for RNA G quadruplexes in regulating alternative splicing. Modulation of G-quadruplex structural integrity may control cellular processes important for tumor progression.
Purpose-The purpose of this paper is to present the sensing mechanism, design issues, performance evaluation and applications for planar capacitive sensors. In the context of characterisation and imaging of a dielectric material under test (MUT), a systematic study of sensor modelling, features and design issues is needed. In addition, the influencing factors on sensitivity distribution, and the effect of conductivity on sensor performance need to be further studied for planar capacitive sensors. Design/methodology/approach-While analytical methods can provide accurate solutions to sensors of simple geometries, numerical modelling is preferred to obtain sensor response to different design parameters and properties of MUT, and to derive the sensitivity distributions of various electrode designs. Several important parameters have been used to evaluate the response of the sensors in different sensing modes. The designs of different planar capacitive sensor arrays are presented and experimentally evaluated. Findings-The response features and design guidelines for planar capacitive sensors in different sensing modes have been summarised, showing that the sensor in the transmission mode or the single-electrode mode is suitable for material characterisation and imaging, while the sensor in the shunt mode is suitable for proximity/displacement measurement. The sensitivity distribution of the sensor depends largely on the geometry of the electrodes. Conductivity causes positive changes for the sensor in the transmission and single-electrode mode, but negative changes for the sensor in the shunt mode. Experimental results confirm that sensing depths of the sensor arrays and the influence of buried conductor on capacitance measurements are in agreement with simulations. Research limitations/implications-Experimental verification is needed when a sensor is designed. Originality/value-This paper provides a comprehensive study for planar capacitive sensors in terms of sensor design, evaluation and applications.
Although changes in alternative splicing have been observed in cancer, their functional contributions still remain largely unclear. Here we report that splice isoforms of the cancer stem cell (CSC) marker CD44 exhibit strikingly opposite functions in breast cancer. Bioinformatic annotation in patient breast cancer in The Cancer Genome Atlas (TCGA) database reveals that the CD44 standard splice isoform (CD44s) positively associates with the CSC gene signatures, whereas the CD44 variant splice isoforms (CD44v) exhibit an inverse association. We show that CD44s is the predominant isoform expressed in breast CSCs. Elimination of the CD44s isoform impairs CSC traits. Conversely, manipulating the splicing regulator ESRP1 to shift alternative splicing from CD44v to CD44s leads to an induction of CSC properties. We further demonstrate that CD44s activates the PDGFRβ/Stat3 cascade to promote CSC traits. These results reveal CD44 isoform specificity in CSC and non-CSC states and suggest that alternative splicing provides functional gene versatility that is essential for distinct cancer cell states and thus cancer phenotypes.
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