Genome-Wide Transcriptional Profiling Reveals MicroRNA-Correlated Genes and Biological Processes in Human Lymphoblastoid Cell Lines

Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and used loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs.To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q<0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological processes related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation.This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations

Mutations in the Human naked cuticle Homolog NKD1 Found in Colorectal Cancer Alter Wnt/Dvl/β-Catenin Signaling

BACKGROUND:Mutation of Wnt signal antagonists Apc or Axin activates beta-catenin signaling in many cancers including the majority of human colorectal adenocarcinomas. The phenotype of apc or axin mutation in the fruit fly Drosophila melanogaster is strikingly similar to that caused by mutation in the segment-polarity gene, naked cuticle (nkd). Nkd inhibits Wnt signaling by binding to the Dishevelled (Dsh/Dvl) family of scaffold proteins that link Wnt receptor activation to beta-catenin accumulation and TCF-dependent transcription, but human NKD genes have yet to be directly implicated in cancer. METHODOLOGY/PRINCIPAL FINDINGS:We identify for the first time mutations in NKD1--one of two human nkd homologs--in a subset of DNA mismatch repair-deficient colorectal tumors that are not known to harbor mutations in other Wnt-pathway genes. The mutant Nkd1 proteins are defective at inhibiting Wnt signaling; in addition, the mutant Nkd1 proteins stabilize beta-catenin and promote cell proliferation, in part due to a reduced ability of each mutant Nkd1 protein to bind and destabilize Dvl proteins. CONCLUSIONS/SIGNIFICANCE:Our data raise the hypothesis that specific NKD1 mutations promote Wnt-dependent tumorigenesis in a subset of DNA mismatch-repair-deficient colorectal adenocarcinomas and possibly other Wnt-signal driven human cancers

Multi-exon deletions of the FBN1 gene in Marfan syndrome

BACKGROUND: Mutations in the fibrillin -1 gene (FBN1) cause Marfan syndrome (MFS), an autosomal dominant multi-system connective tissue disorder. The 200 different mutations reported in the 235 kb, 65 exon-containing gene include only one family with a genomic multi-exon deletion. METHODS: We used long-range RT-PCR for mutation detection and long-range genomic PCR and DNA sequencing for identification of deletion breakpoints, allele-specific transcript analyses to determine stability of the mutant RNA, and pulse-chase studies to quantitate fibrillin synthesis and extracellular matrix deposition in cultured fibroblasts. Southern blots of genomic DNA were probed with three overlapping fragments covering the FBN1 coding exons RESULTS: Two novel multi-exon FBN1 deletions were discovered. Identical nucleotide pentamers were found at or near the intronic breakpoints. In a Case with classic MFS, an in-frame deletion of exons 42 and 43 removed the C-terminal 24 amino acids of the 5(th) LTBP (8-cysteine) domain and the adjacent 25(th) calcium-binding EGF-like (6-cysteine) domain. The mutant mRNA was stable, but fibrillin synthesis and matrix deposition were significantly reduced. A Case with severe childhood-onset MFS has a de novo deletion of exons 44–46 that removed three EGF-like domains. Fibrillin protein synthesis was normal, but matrix deposition was strikingly reduced. No genomic rearrangements were detected by Southern analysis of 18 unrelated MFS samples negative for FBN1 mutation screening. CONCLUSIONS: Two novel deletion cases expand knowledge of mutational mechanisms and genotype/phenotype correlations of fibrillinopathies. Deletions or mutations affecting an LTBP domain may result in unstable mutant protein cleavage products that interfere with microfibril assembly

Metasurface spectrometers beyond resolution-sensitivity constraints

Optical spectroscopy plays an essential role across scientific research and industry for non-contact materials analysis1-3, increasingly through in-situ or portable platforms4-6. However, when considering low-light-level applications, conventional spectrometer designs necessitate a compromise between their resolution and sensitivity7,8, especially as device and detector dimensions are scaled down. Here, we report on a miniaturizable spectrometer platform where light throughput onto the detector is instead enhanced as the resolution is increased. This planar, CMOS-compatible platform is based around metasurface encoders designed to exhibit photonic bound states in the continuum9, where operational range can be altered or extended simply through adjusting geometric parameters. This system can enhance photon collection efficiency by up to two orders of magnitude versus conventional designs; we demonstrate this sensitivity advantage through ultra-low-intensity fluorescent and astrophotonic spectroscopy. This work represents a step forward for the practical utility of spectrometers, affording a route to integrated, chip-based devices that maintain high resolution and SNR without requiring prohibitively long integration times

A Charging Algorithm for the Wireless Rechargeable Sensor Network with Imperfect Charging Channel and Finite Energy Storage

Recently, wireless energy transfer technology becomes a popular way to address energy shortage in wireless sensor networks. The capacity of the mobile wireless charging car (WCV) and the wireless channel between the WCV and the sensor are two important factors influencing the energy efficiency of the wireless sensor network, which has not been well considered. In this paper, we study the energy efficiency of a wireless rechargeable sensor network charged by a finite capacity WCV through an imperfect wireless channel. To estimate the energy efficiency, we first propose a new metric named waste rate, which is defined as a function of the charging channel quality. Then, energy efficiency optimization is modeled as minimizing the waste rate. Through optimizing the distance between the WCV and sensor nodes, the set of optimal charging sensor nodes is obtained. By using the Hamiltonian circle, the nearest neighbor algorithm is proposed to find the traveling path of the WCV. Furthermore, to avoid the untimely death of sensor nodes and the coverage hole, an extended node dynamic replacement strategy is proposed. The simulation results show that the proposed method can reduce the waste rate and the total charging time; i.e., the sum of traveling time and charging delay can be significantly reduced, which indicates that the proposed algorithm can improve the energy efficiency of the network

ARD1/NAA10 acetylation in prostate cancer

© 2018, The Author(s). Prostate cancer (PCa) is the second most common cancer in men. Androgen receptor (AR) signaling pathway plays a crucial role in prostate development and homeostasis. Dysregulation of this pathway activates AR leading to PCa pathogenesis and progression. AR binds testosterone and other male hormones, which then undergoes post-translational modification for AR nuclear translocation and transcriptional activation. AR activation by post-translational modification is thus imperative for PCa cell growth and survival. Identification and understanding of the pathological and mechanistic roles of AR modifications may increase our understanding of AR activation in PCa and provide new therapeutic options. Recently, AR acetylation has been described as an important step for AR activation. Upregulation of several acetyltransferases has been reported to be associated with PCa progression. Herein, we provide a general understanding of AR acetylation, with a special emphasis on ARD1, and potential therapies that may be exploited against the ARD1–AR axis for PCa treatment

From oncolytic peptides to oncolytic polymers: A new paradigm for oncotherapy

Traditional cancer therapy methods, especially those directed against specific intracellular targets or signaling pathways, are not powerful enough to overcome tumor heterogeneity and therapeutic resistance. Oncolytic peptides that can induce membrane lysis-mediated cancer cell death and subsequent anticancer immune responses, has provided a new paradigm for cancer therapy. However, the clinical application of oncolytic peptides is always limited by some factors such as unsatisfactory bio-distribution, poor stability, and off-target toxicity. To overcome these limitations, oncolytic polymers stand out as prospective therapeutic materials owing to their high stability, chemical versatility, and scalable production capacity, which has the potential to drive a revolution in cancer treatment. This review provides an overview of the mechanism and structure-activity relationship of oncolytic peptides. Then the oncolytic peptides-mediated combination therapy and the nano-delivery strategies for oncolytic peptides are summarized. Emphatically, the current research progress of oncolytic polymers has been highlighted. Lastly, the challenges and prospects in the development of oncolytic polymers are discussed