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  • 1
    Publication Date: 2016-06-03
    Description: Gene structure and expression in diplonemid mitochondria are unparalleled. Genes are fragmented in pieces (modules) that are separately transcribed, followed by the joining of module transcripts to contiguous RNAs. Some instances of unique uridine insertion RNA editing at module boundaries were noted, but the extent and potential occurrence of other editing types remained unknown. Comparative analysis of deep transcriptome and genome data from Diplonema papillatum mitochondria reveals ~220 post-transcriptional insertions of uridines, but no insertions of other nucleotides nor deletions. In addition, we detect in total 114 substitutions of cytosine by uridine and adenosine by inosine, amassed into unusually compact clusters. Inosines in transcripts were confirmed experimentally. This is the first report of adenosine-to-inosine editing of mRNAs and ribosomal RNAs in mitochondria. In mRNAs, editing causes mostly amino-acid additions and non-synonymous substitutions; in ribosomal RNAs, it permits formation of canonical secondary structures. Two extensively edited transcripts were compared across four diplonemids. The pattern of uridine-insertion editing is strictly conserved, whereas substitution editing has diverged dramatically, but still rendering diplonemid proteins more similar to other eukaryotic orthologs. We posit that RNA editing not only compensates but also sustains, or even accelerates, ultra-rapid evolution of genome structure and sequence in diplonemid mitochondria.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2014-04-10
    Description: The combination of hyper-CVAD plus nelarabine as frontline therapy in adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma: MD Anderson Cancer Center experience Leukemia 28, 973 (April 2014). doi:10.1038/leu.2013.312 Authors: P Jain, H Kantarjian, F Ravandi, D Thomas, S O'Brien, T Kadia, J Burger, G Borthakur, N Daver, E Jabbour, M Konopleva, J Cortes, N Pemmaraju, M A Kelly, M Cardenas-Turanzas, R Garris & S Faderl
    Print ISSN: 0887-6924
    Electronic ISSN: 1476-5551
    Topics: Medicine
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  • 3
    Publication Date: 2014-04-23
    Description: Programmed translational bypassing is a process whereby ribosomes “ignore” a substantial interval of mRNA sequence. Although discovered 25 y ago, the only experimentally confirmed example of this puzzling phenomenon is expression of the bacteriophage T4 gene 60. Bypassing requires translational blockage at a “takeoff codon” immediately upstream of a stop...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2014-02-27
    Description: Phosphotyrosine (pTyr) signaling is involved in development and maintenance of metazoans’ multicellular body through cell-to-cell communication. Tyrosine kinases (TKs), tyrosine phosphatases, and other proteins relaying the signal compose the cascade. Domain architectures of the pTyr signaling proteins are diverse in metazoans, reflecting their complex intercellular communication. Previous studies had shown that the metazoan-type TKs, as well as other pTyr signaling proteins, were already diversified in the common ancestor of metazoans, choanoflagellates, and filastereans (which are together included in the clade Holozoa) whereas they are absent in fungi and other nonholozoan lineages. However, the earliest-branching holozoans Ichthyosporea and Corallochytrea, as well as the two fungi-related amoebae Fonticula and Nuclearia , have not been studied. Here, we analyze the complete genome sequences of two ichthyosporeans and Fonticula , and RNAseq data of three additional ichthyosporeans, one corallochytrean, and Nuclearia . Both the ichthyosporean and corallochytrean genomes encode a large variety of receptor TKs (RTKs) and cytoplasmic TKs (CTKs), as well as other pTyr signaling components showing highly complex domain architectures. However, Nuclearia and Fonticula have no TK, and show much less diversity in other pTyr signaling components. The CTK repertoires of both Ichthyosporea and Corallochytrea are similar to those of Metazoa, Choanoflagellida, and Filasterea, but the RTK sets are totally different from each other. The complex pTyr signaling equipped with positive/negative feedback mechanism likely emerged already at an early stage of holozoan evolution, yet keeping a high evolutionary plasticity in extracellular signal reception until the co-option of the system for cell-to-cell communication in metazoans.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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  • 5
    Publication Date: 2014-02-28
    Description: Mitochondrial ribosomal RNAs (rRNAs) often display reduced size and deviant secondary structure, and sometimes are fragmented, as are their corresponding genes. Here we report a mitochondrial large subunit rRNA (mt-LSU rRNA) with unprecedented features. In the protist Diplonema , the rnl gene is split into two pieces (modules 1 and 2, 534- and 352-nt long) that are encoded by distinct mitochondrial chromosomes, yet the rRNA is continuous. To reconstruct the post-transcriptional maturation pathway of this rRNA, we have catalogued transcript intermediates by deep RNA sequencing and RT-PCR. Gene modules are transcribed separately. Subsequently, transcripts are end-processed, the module-1 transcript is polyuridylated and the module-2 transcript is polyadenylated. The two modules are joined via trans-splicing that retains at the junction ~26 uridines, resulting in an extent of insertion RNA editing not observed before in any system. The A-tail of trans-spliced molecules is shorter than that of mono-module 2, and completely absent from mitoribosome-associated mt-LSU rRNA. We also characterize putative antisense transcripts. Antisense-mono-modules corroborate bi-directional transcription of chromosomes. Antisense-mt-LSU rRNA, if functional, has the potential of guiding concomitantly trans-splicing and editing of this rRNA. Together, these findings open a window on the investigation of complex regulatory networks that orchestrate multiple and biochemically diverse post-transcriptional events.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2014-12-17
    Description: 5S Ribosomal RNA (5S rRNA) is a universal component of ribosomes, and the corresponding gene is easily identified in archaeal, bacterial and nuclear genome sequences. However, organelle gene homologs ( rrn5 ) appear to be absent from most mitochondrial and several chloroplast genomes. Here, we re-examine the distribution of organelle rrn5 by building mitochondrion- and plastid-specific covariance models (CMs) with which we screened organelle genome sequences. We not only recover all organelle rrn5 genes annotated in GenBank records, but also identify more than 50 previously unrecognized homologs in mitochondrial genomes of various stramenopiles, red algae, cryptomonads, malawimonads and apusozoans, and surprisingly, in the apicoplast (highly derived plastid) genomes of the coccidian pathogens Toxoplasma gondii and Eimeria tenella . Comparative modeling of RNA secondary structure reveals that mitochondrial 5S rRNAs from brown algae adopt a permuted triskelion shape that has not been seen elsewhere. Expression of the newly predicted rrn5 genes is confirmed experimentally in 10 instances, based on our own and published RNA-Seq data. This study establishes that particularly mitochondrial 5S rRNA has a much broader taxonomic distribution and a much larger structural variability than previously thought. The newly developed CMs will be made available via the Rfam database and the MFannot organelle genome annotator.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2016-09-21
    Description: Aim Double reading may be a valuable tool for improving quality of patient care by identifying diagnostic errors before final sign-out, but standard double reading would significantly increase costs of pathology. We assessed the added value of intradepartmental routine double reading of histopathology specimens prior to multidisciplinary meetings. Methods Diagnoses, treatment plans and prognoses of patients are often discussed at multidisciplinary meetings. As part of the daily routine, all pathology specimens to be discussed at upcoming multidisciplinary meetings undergo prior intradepartmental double reading. We identified all histopathology specimens from 2013 that underwent such double reading and determined major and minor discordance rates based on clinical relevance between the initial and consensus sign-out diagnoses. Results We included 6796 histopathology specimens that underwent double reading, representing approximately 8% of all histopathology cases at our institution in 2013. Double reading diagnoses were concordant in 6566 specimens (96.6%). Major and minor discordances were observed in 60 (0.9%) and 170 (2.5%) specimens, respectively. Urology specimens had significantly more discordances than other tissues of origin, Gleason grading of prostate cancer biopsies being the most frequent diagnostic problem. Furthermore, premalignant and malignant cases showed significantly higher discordance rates than the rest. The vast majority (90%) of discordances represented changes within the same diagnostic category (eg, malignant to malignant). Conclusions Routine double reading of histopathology specimens prior to multidisciplinary meetings prevents diagnostic errors. It resulted in about 1% discordant diagnoses of potential clinical significance, indicating that second review is worthwhile in terms of patient safety and quality of patient care.
    Keywords: Prostate cancer, Urological cancer, Histopathology, Clinical diagnostic tests
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 8
    Publication Date: 2016-10-20
    Description: Background Encoded pathology data are key for medical registries and analyses, but pathology information is often expressed as free text. Objective We reviewed and assessed the use of NLP (natural language processing) for encoding pathology documents. Materials and methods Papers addressing NLP in pathology were retrieved from PubMed, Association for Computing Machinery (ACM) Digital Library and Association for Computational Linguistics (ACL) Anthology. We reviewed and summarised the study objectives; NLP methods used and their validation; software implementations; the performance on the dataset used and any reported use in practice. Results The main objectives of the 38 included papers were encoding and extraction of clinically relevant information from pathology reports. Common approaches were word/phrase matching, probabilistic machine learning and rule-based systems. Five papers (13%) compared different methods on the same dataset. Four papers did not specify the method(s) used. 18 of the 26 studies that reported F-measure, recall or precision reported values of over 0.9. Proprietary software was the most frequently mentioned category (14 studies); General Architecture for Text Engineering (GATE) was the most applied architecture overall. Practical system use was reported in four papers. Most papers used expert annotation validation. Conclusions Different methods are used in NLP research in pathology, and good performances, that is, high precision and recall, high retrieval/removal rates, are reported for all of these. Lack of validation and of shared datasets precludes performance comparison. More comparative analysis and validation are needed to provide better insight into the performance and merits of these methods.
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 9
    Publication Date: 2013-02-24
    Description: The most bacteria-like mitochondrial genome known is that of the jakobid flagellate Reclinomonas americana NZ. This genome also encodes the largest known gene set among mitochondrial DNAs (mtDNAs), including the RNA subunit of RNase P (transfer RNA processing), a reduced form of transfer–messenger RNA (translational control), and a four-subunit bacteria-like RNA polymerase, which in other eukaryotes is substituted by a nucleus-encoded, single-subunit, phage-like enzyme. Further, protein-coding genes are preceded by potential Shine–Dalgarno translation initiation motifs. Whether similarly ancestral mitochondrial characters also exist in relatives of R. americana NZ is unknown. Here, we report a comparative analysis of nine mtDNAs from five distant jakobid genera: Andalucia, Histiona, Jakoba, Reclinomonas , and Seculamonas . We find that Andalucia godoyi has an even larger mtDNA gene complement than R. americana NZ. The extra genes are rpl35 (a large subunit mitoribosomal protein) and cox15 (involved in cytochrome oxidase assembly), which are nucleus encoded throughout other eukaryotes. Andalucia cox15 is strikingly similar to its homolog in the free-living α-proteobacterium Tistrella mobilis . Similarly, a long, highly conserved gene cluster in jakobid mtDNAs, which is a clear vestige of prokaryotic operons, displays a gene order more closely resembling that in free-living α-proteobacteria than in Rickettsiales species. Although jakobid mtDNAs, overall, are characterized by bacteria-like features, they also display a few remarkably divergent characters, such as 3'-tRNA editing in Seculamonas ecuadoriensis and genome linearization in Jakoba libera . Phylogenetic analysis with mtDNA-encoded proteins strongly supports monophyly of jakobids with Andalucia as the deepest divergence. However, it remains unclear which α-proteobacterial group is the closest mitochondrial relative.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 10
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 83 (1998), S. 7844-7854 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Thin ZnO films were deposited on various types of substrates with rf magnetron reactive sputtering of a Zn target in pure O2 atmosphere. The layers were characterized by x-ray diffraction and electrical measurements. The piezoelectric strain constant d31 of the films was determined via optical interferometric measurements on the piezoelectrically forced vibration of silicon cantilevers. Because of the high resistivity of the ZnO samples (higher than 109 Ω cm), piezoelectric excitation down to frequencies of 100 Hz was found to be feasible. The relation between the piezoelectric strain constant and the c-axis orientation distribution of the film [obtained from the full width at half maximum of the x-ray rocking curves at the ZnO (002) diffraction] was determined both experimentally and theoretically. It was found that the experimental effective piezoelectric strain constants are, at most, 60% of the value predicted by the theoretical calculations. It is thought that this discrepancy is due to the cancellation of piezoelectric activity by ZnO grains of opposing polarity. The latter effect and other structural properties of the films are discussed in relation to nucleation and growth of sputtered ZnO films. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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