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  • 1
    Publication Date: 2018-04-21
    Description: Optoelectronic devices for information storage and processing are at the heart of optical communication technology due to their significant applications in optical recording and computing. The infrared radiations of 850, 1310, and 1550 nm with low energy dissipation in optical fibers are typical optical communication wavebands. However, optoelectronic devices that could convert and store the infrared data into electrical signals, thereby enabling optical data communications, have not yet been realized. We report an infrared memory device using MoS 2 /PbS van der Waals heterostructures, in which the infrared pulse intrigues a persistent resistance state that hardly relaxes within our experimental time scales (more than 10 4 s). The device fully retrieves the memory state even after powering off for 3 hours, indicating its potential for nonvolatile storage devices. Furthermore, the device presents a reconfigurable switch of 2000 stable cycles. Supported by a theoretical model with quantitative analysis, we propose that the optical memory and the electrical erasing phenomenon, respectively, originate from the localization of infrared-induced holes in PbS and gate voltage pulse-enhanced tunneling of electrons from MoS 2 to PbS. The demonstrated MoS 2 heterostructure–based memory devices open up an exciting field for optoelectronic infrared memory and programmable logic devices.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 2
    Publication Date: 2018-05-08
    Description: Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs play an important role in regulating host anti-mycobacterial defense; however, their role in apoptosis-mediated mycobacterial elimination and inflammatory response remains unclear. In this study, we explored the role of microRNA-27b (miR-27b) in murine macrophage responses to M. tuberculosis infection. We uncovered that the TLR-2/MyD88/NF-B signaling pathway induced the expression of miR-27b and miR-27b suppressed the production of proinflammatory factors and the activity of NF-B, thereby avoiding an excessive inflammation during M. tuberculosis infection. Luciferase reporter assay and Western blotting showed that miR-27b directly targeted Bcl-2–associated athanogene 2 (Bag2) in macrophages. Overexpression of Bag2 reversed miR-27b–mediated inhibition of the production of proinflammatory factors. In addition, miR-27b increased p53-dependent cell apoptosis and the production of reactive oxygen species and decreased the bacterial burden. We also showed that Bag2 interacts with p53 and negatively regulates its activity, thereby controlling cell apoptosis and facilitating bacterial survival. In summary, we revealed a novel role of the miR-27b/Bag2 axis in the regulation of inflammatory response and apoptosis and provide a potential molecular host defense mechanism against mycobacteria.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 3
    Publication Date: 2018-02-28
    Description: Meiosis is a specific type of cell division that is essential for sexual reproduction in most eukaryotes. Mitochondria are crucial cellular organelles that play important roles in reproduction, though the detailed mechanism by which the mitochondrial respiratory chain functions during meiosis remains elusive. Here, we show that components of the respiratory chain (Complexes I–V) play essential roles in meiosis initiation during the sporulation of budding yeast, Saccharomyces cerevisiae . Any functional defects in the Complex I component Ndi1p resulted in the abolishment of sporulation. Further studies revealed that respiratory deficiency resulted in the failure of premeiotic DNA replication due to insufficient IME1 expression. In addition, respiration promoted the expression of RIM101 , whose product inhibits Smp1p , a negative transcriptional regulator of IME1 , to promote meiosis initiation. In summary, our studies unveiled the close relationship between mitochondria and sporulation, and uncover a novel meiosis initiation pathway that is regulated by the respiratory chain.
    Print ISSN: 0016-6731
    Topics: Biology
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  • 4
    Keywords: DISEASE ; UNITED-STATES ; JAPANESE POPULATION ; German ; SEQUENCE VARIANTS ; LOXL1 GENE POLYMORPHISMS ; PSEUDOEXFOLIATION SYNDROME ; GLAUCOMA
    Abstract: Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 x 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: ORA allele = 9.87, P = 2.13 x 10(-217); non-Japanese: ORA allele = 0.49, P = 2.35 x 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.
    Type of Publication: Journal article published
    PubMed ID: 25706626
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  • 5
    Keywords: GENE-EXPRESSION ; DIFFERENTIATION ; BREAST-CANCER ; REPRODUCIBILITY ; PROSTATE-CANCER ; SIGNATURE ; RISK STRATIFICATION ; transcriptome ; EXPRESSION-BASED CLASSIFICATION ; NEUROBLASTOMA PATIENTS
    Abstract: BACKGROUND: Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. RESULTS: We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. CONCLUSIONS: We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.
    Type of Publication: Journal article published
    PubMed ID: 26109056
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  • 6
    Keywords: EXPRESSION ; GENE ; RNA ; CARCINOGENESIS ; POLYMORPHISMS ; SUSCEPTIBILITY ; METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR ; COMMON MUTATION ; FOLATE STATUS ; CHROMOSOME-17 ; BRCA1/2 mutation carriers ; breast/ovarian cancer risk ; MTHFR 677 C 〉 T polymorphism ; PHB 1630 C 〉 T polymorphism ; PROHIBITIN 3'-UNTRANSLATED REGION
    Abstract: BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. METHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C〉T (rs6917) polymorphism and the MTHFR 677 C〉T (rs1801133) polymorphism, respectively. RESULTS: There was no evidence of association between the PHB 1630 C〉T and MTHFR 677 C〉T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C〉T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. CONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.
    Type of Publication: Journal article published
    PubMed ID: 22669161
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  • 7
    Publication Date: 2016-01-28
    Description: Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We found that RNA hydroxymethylation can favor mRNA translation. Tet and hydroxymethylated RNA are found to be most abundant in the Drosophila brain, and Tet-deficient fruitflies suffer impaired brain development, accompanied by decreased RNA hydroxymethylation. This study highlights the distribution, localization, and function of cytosine hydroxymethylation and identifies central roles for this modification in Drosophila.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delatte, Benjamin -- Wang, Fei -- Ngoc, Long Vo -- Collignon, Evelyne -- Bonvin, Elise -- Deplus, Rachel -- Calonne, Emilie -- Hassabi, Bouchra -- Putmans, Pascale -- Awe, Stephan -- Wetzel, Collin -- Kreher, Judith -- Soin, Romuald -- Creppe, Catherine -- Limbach, Patrick A -- Gueydan, Cyril -- Kruys, Veronique -- Brehm, Alexander -- Minakhina, Svetlana -- Defrance, Matthieu -- Steward, Ruth -- Fuks, Francois -- R01 GM089992/GM/NIGMS NIH HHS/ -- T32 CA117846/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):282-5. doi: 10.1126/science.aac5253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Universite Libre de Bruxelles (ULB), Brussels, Belgium. ; Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ, USA. ; Laboratory of Molecular Biology of the Gene, Faculty of Sciences, Universite Libre de Bruxelles, Gosselies, Belgium. ; Institut fur Molekularbiologie und Tumorforschung, Philipps-Universitat Marburg, Marburg, Germany. ; Department of Chemistry, University of Cincinnati, Cincinnati, OH, USA. ; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Universite Libre de Bruxelles (ULB), Brussels, Belgium. ffuks@ulb.ac.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816380" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*abnormalities/metabolism ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; Dioxygenases/genetics/metabolism ; Drosophila melanogaster/genetics/*growth & development/metabolism ; Methylation ; RNA, Messenger/genetics/*metabolism ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2016-04-29
    Description: Transition paths, the fleeting trajectories through the transition states that dominate the dynamics of biomolecular folding reactions, encapsulate the critical information about how structure forms. Owing to their brief duration, however, they have not previously been observed directly. We measured transition paths for both nucleic acid and protein folding, using optical tweezers to observe the microscopic diffusive motion of single molecules traversing energy barriers. The average transit times and the shapes of the transit-time distributions agreed well with theoretical expectations for motion over the one-dimensional energy landscapes reconstructed for the same molecules, validating the physical theory of folding reactions. These measurements provide a first look at the critical microscopic events that occur during folding, opening exciting new avenues for investigating folding phenomena.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neupane, Krishna -- Foster, Daniel A N -- Dee, Derek R -- Yu, Hao -- Wang, Feng -- Woodside, Michael T -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):239-42. doi: 10.1126/science.aad0637.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. ; National Institute for Nanotechnology, National Research Council, Edmonton, Alberta, T6G 2M9, Canada. ; Department of Physics, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. National Institute for Nanotechnology, National Research Council, Edmonton, Alberta, T6G 2M9, Canada. michael.woodside@ualberta.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124461" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry ; Motion ; *Nucleic Acid Conformation ; Optical Tweezers ; Phase Transition ; *Protein Folding ; Protein Structure, Tertiary ; Proteins/*chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2018-01-03
    Description: Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro . The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs. We found that miR-124-3p promoted the anti-inflamed M2 polarization in microglia, and microglial exosomal miR-124-3p inhibited neuronal inflammation in scratch-injured neurons. Further, the mammalian target of rapamycin (mTOR) signaling was implicated as being involved in the regulation of miR-124-3p by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Using the mTOR activator MHY1485 we confirmed that the inhibitory effect of exosomal miR-124-3p on neuronal inflammation was exerted by suppressing the activity of mTOR signaling. PDE4B was predicted to be the target gene of miR-124-3p by pathway analysis. We proved that it was directly targeted by miR-124-3p with a luciferase reporter assay. Using a PDE4B overexpressed lentivirus transfection system, we suggested that miR-124-3p suppressed the activity of mTOR signaling mainly through inhibiting the expression of PDE4B. In addition, exosomal miR-124-3p promoted neurite outgrowth after scratch injury, characterized by an increase on the number of neurite branches and total neurite length, and a decreased expression on RhoA and neurodegenerative proteins [Aβ-peptide and p-Tau]. It also improved the neurologic outcome and inhibited neuroinflammation in mice with rTBI. Taken together, increased miR-124-3p in microglial exosomes after TBI can inhibit neuronal inflammation and contribute to neurite outgrowth via their transfer into neurons. miR-124-3p exerted these effects by targeting PDE4B, thus inhibiting the activity of mTOR signaling. Therefore, miR-124-3p could be a promising therapeutic target for interventions of neuronal inflammation after TBI. miRNAs manipulated microglial exosomes may provide a novel therapy for TBI and other neurologic diseases.—Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., Lei, P. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 10
    Publication Date: 2018-01-31
    Description: Exosomes are small membrane-enclosed vesicles produced by various cells and actively released into the extracellular space. They participate in intercellular communication and transfer of biologically active proteins, lipids, and nucleic acids. Accumulating evidence suggests that exosomes derived from cells infected by some viruses selectively encapsulate viral proteins, genetic materials, or even virions to mediate cell-to-cell communication and/or virus transmission. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the global swine industry since the late 1980s. Recent studies have shown that major proteins secreted from PRRSV-infected cells are exosomal proteins and that the serum-derived exosomes from PRRSV-infected pigs contain viral proteins. However, the role of exosomes in PRRSV infection remains unclear. In this study, purified exosomes isolated from PRRSV-infected cells were shown with reverse transcription-PCR and mass spectrometry to contain viral genomic RNA and partial viral proteins. Furthermore, exosomes from PRRSV-infected cells established productive infection in both PRRSV-susceptible and -nonsusceptible cells. More importantly, exosome-mediated infection was not completely blocked by PRRSV-specific neutralizing antibodies. In summary, this study demonstrated that exosomes can mediate PRRSV transmission and are even resistant to antibody neutralization, identifying a potential immune evasion mechanism utilized by PRRSV. IMPORTANCE Exosomes have recently been characterized as bioactive vesicles that function to promote intercellular communication. The exosomes from virally infected cells containing altered compositions confer numerous novel functionalities. A study of the secretome of cells infected with PRRSV indicated that the exosomal pathway is strongly activated by PRRSV infection. Here, we demonstrate that PRRSV can utilize host exosomes to infect naive healthy cells. Furthermore, exosome-mediated viral transmission is largely resistant to PRRSV-specific neutralizing antibodies. Our study provides novel insights into an alternative mechanism of PRRSV transmission that can compromise the host's anti-PRRSV immune response.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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