An ultrasensitive universal detector based on neutralizer displacement

NASA Astrophysics Data System (ADS)

Das, Jagotamoy; Cederquist, Kristin B.; Zaragoza, Alexandre A.; Lee, Paul E.; Sargent, Edward H.; Kelley, Shana O.

2012-08-01

Diagnostic technologies that can provide the simultaneous detection of nucleic acids for gene expression, proteins for host response and small molecules for profiling the human metabolome will have a significant advantage in providing comprehensive patient monitoring. Molecular sensors that report changes in the electrostatics of a sensor's surface on analyte binding have shown unprecedented sensitivity in the detection of charged biomolecules, but do not lend themselves to the detection of small molecules, which do not carry significant charge. Here, we introduce the neutralizer displacement assay that allows charge-based sensing to be applied to any class of molecule irrespective of the analyte charge. The neutralizer displacement assay starts with an aptamer probe bound to a neutralizer. When analyte binding occurs the neutralizer is displaced, which results in a dramatic change in the surface charge for all types of analytes. We have tested the sensitivity, speed and specificity of this system in the detection of a panel of molecules: (deoxy)ribonucleic acid, ribonucleic acid, cocaine, adenosine triphosphate and thrombin.

The Small Intestinal Epithelia of Beef Steers Differentially Express Sugar Transporter Messenger Ribonucleic Acid in Response to Abomasal Versus Ruminal Infusion of Starch Hydrolysate

USDA-ARS?s Scientific Manuscript database

In mammals, the absorption of mono¬saccharides from small intestinal lumen involves at least 3 sugar transporters (SugT): sodium-dependent glucose transporter 1 (SGLT1; gene SLC5A1) transports glucose and galactose, whereas glucose transporter (GLUT) 5 (GLUT5; gene SLC2A5) transports fructose, acros...

Functional Interplay between Small Non-Coding RNAs and RNA Modification in the Brain.

PubMed

Leighton, Laura J; Bredy, Timothy W

2018-06-07

Small non-coding RNAs are essential for transcription, translation and gene regulation in all cell types, but are particularly important in neurons, with known roles in neurodevelopment, neuroplasticity and neurological disease. Many small non-coding RNAs are directly involved in the post-transcriptional modification of other RNA species, while others are themselves substrates for modification, or are functionally modulated by modification of their target RNAs. In this review, we explore the known and potential functions of several distinct classes of small non-coding RNAs in the mammalian brain, focusing on the newly recognised interplay between the epitranscriptome and the activity of small RNAs. We discuss the potential for this relationship to influence the spatial and temporal dynamics of gene activation in the brain, and predict that further research in the field of epitranscriptomics will identify interactions between small RNAs and RNA modifications which are essential for higher order brain functions such as learning and memory.

Small interfering RNA-mediated suppression of serum response factor, E2-promotor binding factor and survivin in non-small cell lung cancer cell lines by non-viral transfection.

PubMed

Walker, Tobias; Nolte, Andrea; Steger, Volker; Makowiecki, Christina; Mustafi, Migdat; Friedel, Godehard; Schlensak, Christian; Wendel, Hans-Peter

2013-03-01

Serum response factor (SRF), E2F1 and survivin are well-known factors involved in a multitude of cancer-related regulation processes. However, to date, no suitable means has been found to apply their potential in the therapy of non-small cell lung cancer (NSCLC). This study deals with questions of small interfering ribonucleic acid (siRNA) transfection efficiency by a non-viral transfection of NSCLC cell-lines and the power of siRNA to transiently influence cell division by specific silencing. Different NSCLC cell lines were cultured under standard conditions and transfected, with specific siRNA targeting SRF, E2F1 and survivin in a non-viral manner. Cells treated with non-specific siRNA (SCR-siRNA) served as controls. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for messenger RNA (mRNA) expression levels. Additionally, transfection efficiency was evaluated by flow cytometry. The analysis of cell proliferation was determined with a CASY cell counter 3 days after transfection with SRF or SCR-siRNA. Transfection of the NSCLC cell lines with specific siRNAs against SRF, E2F1 and survivin resulted in a very considerable reduction of the intracellular mRNA concentration. CASY confirmation of cell viability demonstrated an excellent survival of the cell lines treated with non-specific siRNA, in contrast to with application of specific siRNA. This study reports a reliable transfectability of NSCLC-cell lines by siRNA, initially in a non-viral manner, and a reproducible knockdown of the focussed targets, consequently leading to the death of the tumour cells. This constitutes a strong candidate for a new assessment strategy in the therapy of non-small cell lung cancer.

Factors affecting citrus tree absorption of double-stranded ribonucleic acid, and RNAi delivery to psyllids

USDA-ARS?s Scientific Manuscript database

Modern molecular biological techniques allow for the design of molecules of ribonucleic acid capable of disrupting key biological processes of pests and diseases. A major requirement for the practical application of ribonucleic acid interference (RNAi) against insect pests is an efficient entry path...

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome

PubMed Central

Ferlaino, Michael; Rogers, Mark F.; Shihab, Hashem A.; Mort, Matthew; Cooper, David N.; Gaunt, Tom R.; Campbell, Colin

2018-01-01

Background Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. Results We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. Conclusions FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome. PMID:28985712

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.

PubMed

Ferlaino, Michael; Rogers, Mark F; Shihab, Hashem A; Mort, Matthew; Cooper, David N; Gaunt, Tom R; Campbell, Colin

2017-10-06

Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.

Evaluation of the reversal of multidrug resistance by MDR1 ribonucleic acid interference in a human colon cancer model using a Renilla luciferase reporter gene and coelenterazine.

PubMed

Jeon, Yong Hyun; Bae, Seon-ae; Lee, Yong Jin; Lee, You La; Lee, Sang-Woo; Yoon, Ghil-Suk; Ahn, Byeong-Cheol; Ha, Jeoung-Hee; Lee, Jaetae

2010-12-01

The reversal effect of multidrug resistance (MDR1) gene expression by adenoviral vector-mediated MDR1 ribonucleic acid interference was assessed in a human colon cancer animal model using bioluminescent imaging with Renilla luciferase (Rluc) gene and coelenterazine, a substrate for Rluc or MDR1 gene expression. A fluorescent microscopic examination demonstrated an increased green fluorescent protein signal in Ad-shMDR1- (recombinant adenovirus that coexpressed MDR1 small hairpin ribonucleic acid [shRNA] and green fluorescent protein) infected HCT-15/Rluc cells in a virus dose-dependent manner. Concurrently, with an increasing administered virus dose (0, 15, 30, 60, and 120 multiplicity of infection), Rluc activity was significantly increased in Ad-shMDR1-infected HCT-15/Rluc cells in a virus dose-dependent manner. In vivo bioluminescent imaging showed about 7.5-fold higher signal intensity in Ad-shMDR1-infected tumors than in control tumors (p < .05). Immunohistologic analysis demonstrated marked reduction of P-glycoprotein expression in infected tumor but not in control tumor. In conclusion, the reversal of MDR1 gene expression by MDR1 shRNA was successfully evaluated by bioluminescence imaging with Rluc activity using an in vivo animal model with a multidrug resistance cancer xenograft.

MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in Drosophila Follicle Cells.

PubMed

Mugat, Bruno; Akkouche, Abdou; Serrano, Vincent; Armenise, Claudia; Li, Blaise; Brun, Christine; Fulga, Tudor A; Van Vactor, David; Pélisson, Alain; Chambeyron, Séverine

2015-05-01

RNA interference-related silencing mechanisms concern very diverse and distinct biological processes, from gene regulation (via the microRNA pathway) to defense against molecular parasites (through the small interfering RNA and the Piwi-interacting RNA pathways). Small non-coding RNAs serve as specificity factors that guide effector proteins to ribonucleic acid targets via base-pairing interactions, to achieve transcriptional or post-transcriptional regulation. Because of the small sequence complementarity required for microRNA-dependent post-transcriptional regulation, thousands of microRNA (miRNA) putative targets have been annotated in Drosophila. In Drosophila somatic ovarian cells, genomic parasites, such as transposable elements (TEs), are transcriptionally repressed by chromatin changes induced by Piwi-interacting RNAs (piRNAs) that prevent them from invading the germinal genome. Here we show, for the first time, that a functional miRNA pathway is required for the piRNA-mediated transcriptional silencing of TEs in this tissue. Global miRNA depletion, caused by tissue- and stage-specific knock down of drosha (involved in miRNA biogenesis), AGO1 or gawky (both responsible for miRNA activity), resulted in loss of TE-derived piRNAs and chromatin-mediated transcriptional de-silencing of TEs. This specific TE de-repression was also observed upon individual titration (by expression of the complementary miRNA sponge) of two miRNAs (miR-14 and miR-34) as well as in a miR-14 loss-of-function mutant background. Interestingly, the miRNA defects differentially affected TE- and 3' UTR-derived piRNAs. To our knowledge, this is the first indication of possible differences in the biogenesis or stability of TE- and 3' UTR-derived piRNAs. This work is one of the examples of detectable phenotypes caused by loss of individual miRNAs in Drosophila and the first genetic evidence that miRNAs have a role in the maintenance of genome stability via piRNA-mediated TE repression.

PHAGE FORMATION IN STAPHYLOCOCCUS MUSCAE CULTURES

PubMed Central

Price, Winston H.

1952-01-01

1. The synthesis of ribonucleic acid, desoxyribomicleic acid, and protein in S. muscae has been studied: (a) during the lag phase, (b) during the early log phase, and (c) while the cells are forming an adaptive enzyme for lactose utilization. 2. During the lag phase there may be a 60 per cent increase in ribonucleic acid and protein and a 50 per cent increase in dry weight without a change in cell count, as determined microscopically, or an increase in turbidity. 3. During this period, the increase in protein closely parallels the increase in ribonucleic acid, in contrast to desoxyribonucleic acid, which begins to be synthesized about 45 minutes after the protein and ribonucleic acid have begun to increase. 4. The RNA N/protein N ratio is proportional to the growth rate of all S. muscae strains studied. 5. While the RNA content per cell during the early log phase depends upon the growth rate, the DNA content per cell is fairly constant irrespective of the growth rate of the cell. 6. Resting cells of S. muscae have approximately the same RNA content per cell irrespective of their prospective growth rate. 7. While the cells are adapting to lactose, during which time there is little or no cellular division, there is never an increase of protein without a simultaneous increase in ribonucleic acid, the RNA N/protein N ratio during these intervals being approximately 0.15. 8. Lactose-adapting cells show a loss of ribonucleic acid. The purines-pyrimidines of the ribonucleic acid can be recovered in the cold 5 per cent trichloroacetic acid fraction, but the ribose component is completely lost from the system. 9. The significance of these results is discussed in relation to the importance of ribonucleic acid for protein synthesis. PMID:14955617

Complete genome sequence of a novel genotype of squash mosaic virus

USDA-ARS?s Scientific Manuscript database

Complete genome sequence of a novel genotype of Squash mosaic virus (SqMV) infecting squash plants in Spain was obtained using deep sequencing of small ribonucleic acids and assembly. The low nucleotide sequence identities, with 87-88% on RNA1 and 84-86% on RNA2 to known SqMV isolates, suggest a new...

Progressive changes in non-coding RNA profile in leucocytes with age

PubMed Central

Muñoz-Culla, Maider; Irizar, Haritz; Gorostidi, Ana; Alberro, Ainhoa; Osorio-Querejeta, Iñaki; Ruiz-Martínez, Javier; Olascoaga, Javier; de Munain, Adolfo López; Otaegui, David

2017-01-01

It has been observed that immune cell deterioration occurs in the elderly, as well as a chronic low-grade inflammation called inflammaging. These cellular changes must be driven by numerous changes in gene expression and in fact, both protein-coding and non-coding RNA expression alterations have been observed in peripheral blood mononuclear cells from elder people. In the present work we have studied the expression of small non-coding RNA (microRNA and small nucleolar RNA -snoRNA-) from healthy individuals from 24 to 79 years old. We have observed that the expression of 69 non-coding RNAs (56 microRNAs and 13 snoRNAs) changes progressively with chronological age. According to our results, the age range from 47 to 54 is critical given that it is the period when the expression trend (increasing or decreasing) of age-related small non-coding RNAs is more pronounced. Furthermore, age-related miRNAs regulate genes that are involved in immune, cell cycle and cancer-related processes, which had already been associated to human aging. Therefore, human aging could be studied as a result of progressive molecular changes, and different age ranges should be analysed to cover the whole aging process. PMID:28448962

Ultra-low input transcriptomics reveal the spore functional content and phylogenetic affiliations of poorly studied arbuscular mycorrhizal fungi

PubMed Central

Beaudet, Denis; Chen, Eric C H; Mathieu, Stephanie; Yildirir, Gokalp; Ndikumana, Steve; Dalpé, Yolande; Séguin, Sylvie; Farinelli, Laurent; Stajich, Jason E; Corradi, Nicolas

2018-01-01

Abstract Arbuscular mycorrhizal fungi (AMF) are a group of soil microorganisms that establish symbioses with the vast majority of land plants. To date, generation of AMF coding information has been limited to model genera that grow well axenically; Rhizoglomus and Gigaspora. Meanwhile, data on the functional gene repertoire of most AMF families is non-existent. Here, we provide primary large-scale transcriptome data from eight poorly studied AMF species (Acaulospora morrowiae, Diversispora versiforme, Scutellospora calospora, Racocetra castanea, Paraglomus brasilianum, Ambispora leptoticha, Claroideoglomus claroideum and Funneliformis mosseae) using ultra-low input ribonucleic acid (RNA)-seq approaches. Our analyses reveals that quiescent spores of many AMF species harbour a diverse functional diversity and solidify known evolutionary relationships within the group. Our findings demonstrate that RNA-seq data obtained from low-input RNA are reliable in comparison to conventional RNA-seq experiments. Thus, our methodology can potentially be used to deepen our understanding of fungal microbial function and phylogeny using minute amounts of RNA material. PMID:29211832

Deciphering the Role of the Barr Body in Malignancy: An insight into head and neck cancer.

PubMed

Sharma, Deepti; Koshy, George; Gupta, Shruti; Sharma, Bhushan; Grover, Sonal

2017-11-01

X chromosome inactivation is the epitome of epigenetic regulation and long non-coding ribonucleic acid function. The differentiation status of cells has been ascribed to X chromosome activity, with two active X chromosomes generally only observed in undifferentiated or poorly differentiated cells. Recently, several studies have indicated that the reactivation of an inactive X chromosome or X chromosome multiplication correlates with the development of malignancy; however, this concept is still controversial. This review sought to shed light on the role of the X chromosome in cancer development. In particular, there is a need for further exploration of the expression patterns of X-linked genes in cancer cells, especially those in head and neck squamous cell carcinoma (HNSCC), in order to identify different prognostic subpopulations with distinct clinical implications. This article proposes a functional relationship between the loss of the Barr body and the disproportional expression of X-linked genes in HNSCC development.

Reovirus-induced Ribonucleic Acid Polymerase

PubMed Central

Watanabe, Y.; Gauntt, C. J.; Graham, A. F.

1968-01-01

A virus-induced ribonucleic acid (RNA) polymerase activity was found in L cells infected with type 3 reovirus. Most of the enzyme is associated with the “large particle” fraction of the infected cells. The enzyme first appeared at 3 to 5 hr after infection and increased in amount until 7 to 9 hr. All four ribonucleoside triphosphates are incorporated in vitro into an acid-insoluble form by the enzyme. The major part of the product formed in vitro is a double-stranded RNA indistinguishable from viral RNA by electrophoresis on polyacrylamide gel. Approximately 40% of the product is a single-stranded RNA of relatively small molecular weight. More than 95% of the nucleotides incorporated into double-stranded RNA by the enzyme are bound in internal 3′-5′-phosphodiester linkages extending back from both 3′- and 5′-termini of the RNA strands. PMID:5725319

Exploring the trans-acting short interfering RNAs (ta-siRNAs) technology for virus control in plants

USDA-ARS?s Scientific Manuscript database

Small ribonucleic acid (RNAs) (~20-24nt) processed from double-stranded RNA in plants can trigger degradation of the target mRNAs in cytoplasm or de novo DNA methylation in nucleus leading to gene silencing. Trans-acting short-interfering RNAs (ta-siRNAs) have been shown to enhance the target mRNA d...

Identification of small non-coding RNA classes expressed in swine whole blood during HP-PRRSV infection

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

Differential expression of small non-coding RNAs in serum from cattle challenged with viruses causing bovine respiratory disease

USDA-ARS?s Scientific Manuscript database

MicroRNAs and tRNA-derived RNA fragments (tRFs) are the two most abundant groups of small non-coding RNAs. The potential for microRNAs and tRFs to be used as pathogen exposure indicators is yet to be fully explored. Our objective was to identify microRNAs and tRFs in cattle challenged with a non-cy...

DNA rearrangements directed by non-coding RNAs in ciliates

PubMed Central

Mochizuki, Kazufumi

2013-01-01

Extensive programmed rearrangement of DNA, including DNA elimination, chromosome fragmentation, and DNA descrambling, takes place in the newly developed macronucleus during the sexual reproduction of ciliated protozoa. Recent studies have revealed that two distant classes of ciliates use distinct types of non-coding RNAs to regulate such DNA rearrangement events. DNA elimination in Tetrahymena is regulated by small non-coding RNAs that are produced and utilized in an RNAi-related process. It has been proposed that the small RNAs produced from the micronuclear genome are used to identify eliminated DNA sequences by whole-genome comparison between the parental macronucleus and the micronucleus. In contrast, DNA descrambling in Oxytricha is guided by long non-coding RNAs that are produced from the parental macronuclear genome. These long RNAs are proposed to act as templates for the direct descrambling events that occur in the developing macronucleus. Both cases provide useful examples to study epigenetic chromatin regulation by non-coding RNAs. PMID:21956937

Small non-coding RNAs (sncRNA) regulate gene silencing and modify homeostatic status in animals faced with porcine reproductive and respiratory syndrome virus (PRRSV)

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

Encephalomyocarditis Virus Ribonucleic Acid Polymerase Associated with 150S Cytoplasmic Particles

PubMed Central

Bases, Robert; Tarikas, Helgi

1969-01-01

Cytoplasmic particles which sedimented at 150S were the smallest structures containing detectable viral ribonucleic acid polymerase in mouse cells infected with encephalomyocarditis virus. PMID:4307906

How does hydroxyl introduction influence the double helical structure: the stabilization of an altritol nucleic acid:ribonucleic acid duplex

PubMed Central

Ovaere, Margriet; Sponer, Jiri; Sponer, Judit E.; Herdewijn, Piet; Van Meervelt, Luc

2012-01-01

Altritol nucleic acids (ANAs) are a promising new tool in the development of artificial small interfering ribonucleic acids (siRNAs) for therapeutical applications. To mimic the siRNA:messenger RNA (mRNA) interactions, the crystal structure of the ANA:RNA construct a(CCGUAAUGCC-P):r(GGCAUUACGG) was determined to 1.96 Å resolution which revealed the hybrid to form an A-type helix. As this A-form is a major requirement in the RNAi process, this crystal structure confirms the potential of altritol-modified siRNAs. Moreover, in the ANA strands, a new type of intrastrand interactions was found between the O2′ hydroxyl group of one residue and the sugar ring O4′ atom of the next residue. These interactions were further investigated by quantum chemical methods. Besides hydration effects, these intrastrand hydrogen bonds may also contribute to the stability of ANA:RNA duplexes. PMID:22638588

First report of Sapajus cay naturally infected by Trypanosoma cruzi in San Pedro Department, Paraguay.

PubMed

Acosta, Nidia; Miret, Jorge; López, Elsa; Schinini, Alicia

2016-08-29

To verify the occurrence of natural Trypanosoma cruzi infection in non-human primates from a rural endemic area of the east region of Paraguay, xenodiagnosis was performed in 35 animals belonging to two species. For genotyping and T. cruzi discrete typing unit (DTU) assignment, a combination of four markers was used, including amplification products of the small (18S) and large (24Sα) subunits of ribosomal ribonucleic acid gene, the intergenic region of mini-exon gene and the heat shock protein 60 Eco-RV polymerase chain reaction-restriction fragment length polymorphism (HSP60/EcoRV-PCR-RFLP). One specimen of Sapajus cay was found positive and infected by the DTU TcII. This result constitutes the first record of natural T. cruzi infection in a sylvatic monkey in Paraguay, harbouring a DTU associated with severe Chagas disease in humans.

Discovery of a new genotype of Squash mosaic virus through deep sequencing of small RNAs and development of a qRT-PCR for broad spectrum detection

USDA-ARS?s Scientific Manuscript database

Squash mosaic virus (SqMV), a seed-borne virus belonging to the genus Commovirus in the family Comoviridae, could cause a serious yield loss on cucurbit crops worldwide. SqMV has a bipartite single-stranded ribonucleic acid (RNA) genome (RNA-1 and RNA-2) encapsidated separately with two capsid prote...

Inactivation of Encephalomyocarditis Virus in Aerosols: Fate of Virus Protein and Ribonucleic Acid

PubMed Central

De Jong, J. C.; Harmsen, M.; Trouwborst, T.; Winkler, K. C.

1974-01-01

After aerosolization at relative humidities of 50% or lower, encephalomyocarditis virus is rapidly inactivated. In this process the protein coat of the virion is damaged. This appears as a loss of hemagglutination activity and loss of affinity for hemagglutination inhibiting antibodies. The ribonucleic acid of the virus retains its infectivity but it becomes susceptible to ribonuclease. It sediments in sucrose gradients when centrifuged at high speed with the same velocity as free infectious ribonucleic acid extracted with phenol from intact encephalomyocarditis virus. PMID:4358862

Ultra-low input transcriptomics reveal the spore functional content and phylogenetic affiliations of poorly studied arbuscular mycorrhizal fungi.

PubMed

Beaudet, Denis; Chen, Eric C H; Mathieu, Stephanie; Yildirir, Gokalp; Ndikumana, Steve; Dalpé, Yolande; Séguin, Sylvie; Farinelli, Laurent; Stajich, Jason E; Corradi, Nicolas

2017-12-02

Arbuscular mycorrhizal fungi (AMF) are a group of soil microorganisms that establish symbioses with the vast majority of land plants. To date, generation of AMF coding information has been limited to model genera that grow well axenically; Rhizoglomus and Gigaspora. Meanwhile, data on the functional gene repertoire of most AMF families is non-existent. Here, we provide primary large-scale transcriptome data from eight poorly studied AMF species (Acaulospora morrowiae, Diversispora versiforme, Scutellospora calospora, Racocetra castanea, Paraglomus brasilianum, Ambispora leptoticha, Claroideoglomus claroideum and Funneliformis mosseae) using ultra-low input ribonucleic acid (RNA)-seq approaches. Our analyses reveals that quiescent spores of many AMF species harbour a diverse functional diversity and solidify known evolutionary relationships within the group. Our findings demonstrate that RNA-seq data obtained from low-input RNA are reliable in comparison to conventional RNA-seq experiments. Thus, our methodology can potentially be used to deepen our understanding of fungal microbial function and phylogeny using minute amounts of RNA material. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

[Relevance of long non-coding RNAs in tumour biology].

PubMed

Nagy, Zoltán; Szabó, Diána Rita; Zsippai, Adrienn; Falus, András; Rácz, Károly; Igaz, Péter

2012-09-23

The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is transcribed. Beside small RNAs (including microRNAs) more and more data are disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length that are implicated in the regulation of several basic molecular processes (cell proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of these long non-coding RNAs have been associated with human tumours, including H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in various neoplasms relative to healthy tissues. Long non-coding RNAs may represent novel markers of molecular diagnostics and they might even turn out to be targets of therapeutic intervention.

Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.

PubMed

Zhang, Yunfang; Zhang, Xudong; Shi, Junchao; Tuorto, Francesca; Li, Xin; Liu, Yusheng; Liebers, Reinhard; Zhang, Liwen; Qu, Yongcun; Qian, Jingjing; Pahima, Maya; Liu, Ying; Yan, Menghong; Cao, Zhonghong; Lei, Xiaohua; Cao, Yujing; Peng, Hongying; Liu, Shichao; Wang, Yue; Zheng, Huili; Woolsey, Rebekah; Quilici, David; Zhai, Qiwei; Li, Lei; Zhou, Tong; Yan, Wei; Lyko, Frank; Zhang, Ying; Zhou, Qi; Duan, Enkui; Chen, Qi

2018-05-01

The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2,3 and metabolic disorders 4-6 . How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m 5 C, m 2 G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m 5 C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.

Characterization of a Fluorescent Protein Reporter System

DTIC Science & Technology

2008-03-01

pathways are initiated with the binding of a small molecule to a catalytic ribonucleic acid molecule (RNA), called a ribozyme (Thodima et al., 2006). The... ribozyme is part of a larger RNA construct, called a riboswitch, which initiates translation of a specific genetic sequence on a plasmid (circular...protein gene. Yen et al. (2004) reported insertion of a self-cleaving ribozyme upstream of the reporter gene. In the absence of a regulator (“off

Towards the elements of successful insect Ribonucleic acid interference (RNAi)

USDA-ARS?s Scientific Manuscript database

Ribonucleic acid interference (RNAi), the sequence-specific suppression of gene expression, offers great opportunities for insect science, especially to analyze gene function, manage pest populations, and reduce disease pathogens. The accumulating body of literature on insect RNAi has revealed that ...

Crosstalk between the Notch signaling pathway and non-coding RNAs in gastrointestinal cancers

PubMed Central

Pan, Yangyang; Mao, Yuyan; Jin, Rong; Jiang, Lei

2018-01-01

The Notch signaling pathway is one of the main signaling pathways that mediates direct contact between cells, and is essential for normal development. It regulates various cellular processes, including cell proliferation, apoptosis, migration, invasion, angiogenesis and metastasis. It additionally serves an important function in tumor progression. Non-coding RNAs mainly include small microRNAs, long non-coding RNAs and circular RNAs. At present, a large body of literature supports the biological significance of non-coding RNAs in tumor progression. It is also becoming increasingly evident that cross-talk exists between Notch signaling and non-coding RNAs. The present review summarizes the current knowledge of Notch-mediated gastrointestinal cancer cell processes, and the effect of the crosstalk between the three major types of non-coding RNAs and the Notch signaling pathway on the fate of gastrointestinal cancer cells. PMID:29285185

Discrimination of Self and Non-Self Ribonucleic Acids

PubMed Central

Gebhardt, Anna; Laudenbach, Beatrice T.

2017-01-01

Most virus infections are controlled through the innate and adaptive immune system. A surprisingly limited number of so-called pattern recognition receptors (PRRs) have the ability to sense a large variety of virus infections. The reason for the broad activity of PRRs lies in the ability to recognize viral nucleic acids. These nucleic acids lack signatures that are present in cytoplasmic cellular nucleic acids and thereby marking them as pathogen-derived. Accumulating evidence suggests that these signatures, which are predominantly sensed by a class of PRRs called retinoic acid-inducible gene I (RIG-I)-like receptors and other proteins, are not unique to viruses but rather resemble immature forms of cellular ribonucleic acids generated by cellular polymerases. RIG-I-like receptors, and other cellular antiviral proteins, may therefore have mainly evolved to sense nonprocessed nucleic acids typically generated by primitive organisms and pathogens. This capability has not only implications on induction of antiviral immunity but also on the function of cellular proteins to handle self-derived RNA with stimulatory potential. PMID:28475460

Genome defense against exogenous nucleic acids in eukaryotes by non-coding DNA occurs through CRISPR-like mechanisms in the cytosol and the bodyguard protection in the nucleus.

PubMed

Qiu, Guo-Hua

2016-01-01

In this review, the protective function of the abundant non-coding DNA in the eukaryotic genome is discussed from the perspective of genome defense against exogenous nucleic acids. Peripheral non-coding DNA has been proposed to act as a bodyguard that protects the genome and the central protein-coding sequences from ionizing radiation-induced DNA damage. In the proposed mechanism of protection, the radicals generated by water radiolysis in the cytosol and IR energy are absorbed, blocked and/or reduced by peripheral heterochromatin; then, the DNA damage sites in the heterochromatin are removed and expelled from the nucleus to the cytoplasm through nuclear pore complexes, most likely through the formation of extrachromosomal circular DNA. To strengthen this hypothesis, this review summarizes the experimental evidence supporting the protective function of non-coding DNA against exogenous nucleic acids. Based on these data, I hypothesize herein about the presence of an additional line of defense formed by small RNAs in the cytosol in addition to their bodyguard protection mechanism in the nucleus. Therefore, exogenous nucleic acids may be initially inactivated in the cytosol by small RNAs generated from non-coding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. Exogenous nucleic acids may enter the nucleus, where some are absorbed and/or blocked by heterochromatin and others integrate into chromosomes. The integrated fragments and the sites of DNA damage are removed by repetitive non-coding DNA elements in the heterochromatin and excluded from the nucleus. Therefore, the normal eukaryotic genome and the central protein-coding sequences are triply protected by non-coding DNA against invasion by exogenous nucleic acids. This review provides evidence supporting the protective role of non-coding DNA in genome defense. Copyright © 2016 Elsevier B.V. All rights reserved.

Small non-coding RNAs in streptomycetes.

PubMed

Heueis, Nona; Vockenhuber, Michael-Paul; Suess, Beatrix

2014-01-01

Streptomycetes are Gram-positive, GC-rich, soil dwelling bacteria, occurring ubiquitary throughout nature. They undergo extensive morphological changes from spores to filamentous mycelia and produce a plethora of secondary metabolites. Owing to their complex life cycle, streptomycetes require efficient regulatory machinery for the control of gene expression. Therefore, they possess a large diversity of regulators. Within this review we summarize the current knowledge about the importance of small non-coding RNA for the control of gene expression in these organisms.

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report.

PubMed

Li, Dongqi; He, Chuanchun; Xia, Yaoxiong; Du, Yaxi; Zhang, Jing

2018-04-23

Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients. In June 2016, a 52-year-old Chinese man presented with human immunodeficiency virus and lung adenocarcinoma (T1bN3M1b). From November 2016 to December 2016, systemic chemotherapy and palliative radiotherapy for bone metastasis of femoral neck were carried out, but the tumor progressed. In January 2017, after immunochemistry detection of programmed death-1 and programmed death-ligand 1 expression (both > 50%), pembrolizumab was started. Three weeks after pembrolizumab, we combined stereotactic body radiotherapy for the primary lung tumor. He received no comfort and his CD4 lymphocyte count was stable. Human immunodeficiency virus-ribonucleic acid remained below the limits of detection. In March 2017, after three cycles of pembrolizumab and 5 weeks of stereotactic body radiotherapy therapy, he suddenly presented with palpitations. Emergency computed tomography scanning showed massive pericardial effusion and interstitial pneumonia. So we interrupted the pembrolizumab use and initiated treatment with prednisolone 1 mg/kg; however, the tumor progressed. Then, his CD4 lymphocyte count declined. Finally he died in June 2017 due to dyscrasia. Pembrolizumab combined with SBRT therapy for patients with human immunodeficiency virus infection and non-small cell lung cancer may lead to serious immune-related adverse events and more clinical trials are needed.

Comparison of methods of extracting messenger Ribonucleic Acid from ejaculated Porcine (Sus Scrofa) Spermatozoa

USDA-ARS?s Scientific Manuscript database

H. D. Guthrie, G.R. Welch, and L. A. Blomberg. Comparison of Methods of Extracting Messenger Ribonucleic Acid from Ejaculated Porcine (Sus Scrofa) Spermatozoa. Biotechnology and Germplasm Laboratory, Agricultural Research Service U. S. Department of Agriculture, Beltsville, MD 20705 The purpos...

Parameters on plant absortion of double-stranded Ribonucleic acid, dsRNA

USDA-ARS?s Scientific Manuscript database

Efficient absorption of double-stranded Ribonucleic acid, dsRNA, into citrus is critical for effective psyllid management by RNA interference, RNAi. Parameters which might affect absorption into citrus trees and subsequent ingestion by Asian citrus psyllid were evaluated. Age of leaves, variety of c...

Small RNAs, big impact: small RNA pathways in transposon control and their effect on the host stress response.

PubMed

Wheeler, Bayly S

2013-12-01

Transposons are mobile genetic elements that are a major constituent of most genomes. Organisms regulate transposable element expression, transposition, and insertion site preference, mitigating the genome instability caused by uncontrolled transposition. A recent burst of research has demonstrated the critical role of small non-coding RNAs in regulating transposition in fungi, plants, and animals. While mechanistically distinct, these pathways work through a conserved paradigm. The presence of a transposon is communicated by the presence of its RNA or by its integration into specific genomic loci. These signals are then translated into small non-coding RNAs that guide epigenetic modifications and gene silencing back to the transposon. In addition to being regulated by the host, transposable elements are themselves capable of influencing host gene expression. Transposon expression is responsive to environmental signals, and many transposons are activated by various cellular stresses. TEs can confer local gene regulation by acting as enhancers and can also confer global gene regulation through their non-coding RNAs. Thus, transposable elements can act as stress-responsive regulators that control host gene expression in cis and trans.

The Ribosome Shape Directs mRNA Translocation through Entrance and Exit Dynamics

USDA-ARS?s Scientific Manuscript database

The protein-synthesizing ribosome undergoes large motions to effect the translocation of tRNAs (transfer ribonucleic acids) and mRNA (messenger ribonucleic acid); here the domain motions of this system are explored with a coarse-grained elastic network model using normal mode analysis. Crystal struc...

Small non-coding RNA profiling in human biofluids and surrogate tissues from healthy individuals: description of the diverse and most represented species.

PubMed

Ferrero, Giulio; Cordero, Francesca; Tarallo, Sonia; Arigoni, Maddalena; Riccardo, Federica; Gallo, Gaetano; Ronco, Guglielmo; Allasia, Marco; Kulkarni, Neha; Matullo, Giuseppe; Vineis, Paolo; Calogero, Raffaele A; Pardini, Barbara; Naccarati, Alessio

2018-01-09

The role of non-coding RNAs in different biological processes and diseases is continuously expanding. Next-generation sequencing together with the parallel improvement of bioinformatics analyses allows the accurate detection and quantification of an increasing number of RNA species. With the aim of exploring new potential biomarkers for disease classification, a clear overview of the expression levels of common/unique small RNA species among different biospecimens is necessary. However, except for miRNAs in plasma, there are no substantial indications about the pattern of expression of various small RNAs in multiple specimens among healthy humans. By analysing small RNA-sequencing data from 243 samples, we have identified and compared the most abundantly and uniformly expressed miRNAs and non-miRNA species of comparable size with the library preparation in four different specimens (plasma exosomes, stool, urine, and cervical scrapes). Eleven miRNAs were commonly detected among all different specimens while 231 miRNAs were globally unique across them. Classification analysis using these miRNAs provided an accuracy of 99.6% to recognize the sample types. piRNAs and tRNAs were the most represented non-miRNA small RNAs detected in all specimen types that were analysed, particularly in urine samples. With the present data, the most uniformly expressed small RNAs in each sample type were also identified. A signature of small RNAs for each specimen could represent a reference gene set in validation studies by RT-qPCR. Overall, the data reported hereby provide an insight of the constitution of the human miRNome and of other small non-coding RNAs in various specimens of healthy individuals.

Assessment of psyllid double-stranded Ribonucleic acid, RNA, off-target effects on a ladybird beetle predator

USDA-ARS?s Scientific Manuscript database

Development of Ribonucleic acid interference, RNAi against insect pests needs to show species target specificity so that beneficial insects remain unharmed, as many pest insects are a food source for predatory insects like lady beetles. We evaluated an RNAi product specific to Asian citrus psyllid f...

The long non-coding RNA LSINCT5 promotes malignancy in non-small cell lung cancer by stabilizing HMGA2.

PubMed

Tian, Yuheng; Zhang, Lina; Chen, Shuwen; Ma, Yuan; Liu, Yanyan

2018-06-08

Long non-coding RNAs (lncRNAs) can actively participate in tumorigenesis in various cancers. However, the involvement of lncRNA long stress induced non-coding transcripts 5 (LSINCT5) in non-small cell lung cancer (NSCLC) remains largely unknown. Here we showed a novel lncRNA signature in NSCLC through lncRNA profiling. Increased LSINCT5 expression positively correlates with malignant clinicopathological features and poor survival. LSINCT5 can promote migration and viability of various NSCLC cells in vitro and also enhance lung cancer progression in vivo. RNA immunoprecipitation followed by mass spectrometry has identified that LSINCT5 interacts with HMGA2. This physical interaction can increase the stability of HMGA2 by inhibiting proteasome-mediated degradation. Therefore, LSINCT5 may possibly contribute to NSCLC tumorigenesis by stabilizing the oncogenic factor of HMGA2. This novel LSINCT5/HMGA2 axis can modulate lung cancer progression and might be a promising target for pharmacological intervention.

Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata.

PubMed

Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

2013-01-07

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem-loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping-pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration.

Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata

PubMed Central

Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

2013-01-01

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem–loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping–pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration. PMID:23166307

Presence of gonadotropin-releasing hormone and its messenger ribonucleic acid in human ovarian epithelial carcinoma.

PubMed

Ohno, T; Imai, A; Furui, T; Takahashi, K; Tamaya, T

1993-09-01

The purpose of this study was to investigate the expression of gonadotropin-releasing hormone messenger ribonucleic acid and the presence of gonadotropin-releasing hormone in human ovarian carcinoma known to have gonadotropin-releasing hormone binding sites and to be affected by gonadotropin-releasing hormone analog. Human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines were examined. Gonadotropin-releasing hormone was determined by a radioimmunoassay and a bioassay. Gonadotropin-releasing hormone messenger ribonucleic acid was determined by reverse transcription polymerase chain reaction using oligonucleotide primers synthesized according to the published human gonadotropin-releasing hormone sequence. Gonadotropin-releasing hormone was shown to be present in extracts of ovarian mucinous cystadenocarcinoma sample (0.8 +/- 0.12 pg/mg of protein) and ovarian adenocarcinoma cell line SK-OV3 (0.92 +/- 0.17 pg/mg of protein) but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic gonadotropin-releasing hormone. Gonadotropin-releasing hormone messenger ribonucleic acid was detected in two of two mucinous cystadenocarcinoma specimens, one of one serous cystadenocarcinoma, and SK-OV3 cells but not in the dysgerminoma, mucinous cystadenoma, and normal ovary and placenta. The demonstration of gonadotropin-releasing hormone and its messenger ribonucleic acid raises the possibility that gonadotropin-releasing hormone may play an autocrine regulatory role in the growth of ovarian carcinoma.

Structural determinants of an internal ribosome entry site that direct translational reading frame selection

PubMed Central

Ren, Qian; Au, Hilda H.T.; Wang, Qing S.; Lee, Seonghoon; Jan, Eric

2014-01-01

The dicistrovirus intergenic internal ribosome entry site (IGR IRES) directly recruits the ribosome and initiates translation using a non-AUG codon. A subset of IGR IRESs initiates translation in either of two overlapping open reading frames (ORFs), resulting in expression of the 0 frame viral structural polyprotein and an overlapping +1 frame ORFx. A U–G base pair adjacent to the anticodon-like pseudoknot of the IRES directs +1 frame translation. Here, we show that the U-G base pair is not absolutely required for +1 frame translation. Extensive mutagenesis demonstrates that 0 and +1 frame translation can be uncoupled. Ribonucleic acid (RNA) structural probing analyses reveal that the mutant IRESs adopt distinct conformations. Toeprinting analysis suggests that the reading frame is selected at a step downstream of ribosome assembly. We propose a model whereby the IRES adopts conformations to occlude the 0 frame aminoacyl-tRNA thereby allowing delivery of the +1 frame aminoacyl-tRNA to the A site to initiate translation of ORFx. This study provides a new paradigm for programmed recoding mechanisms that increase the coding capacity of a viral genome. PMID:25038250

[Studies on the interaction between RNA with neutral red and determination of RNA by spectrophotometry].

PubMed

Si, Wen-Hui

2007-06-01

An analytical method for the determination of ribonucleic acid by spectrophotometry was established. At the maximum absorption wavelength for neutral red in B-R buffer solution, and under the best conditions, the decrease in the absorbance was linear with the amount of ribonucleic acid. The linearity range was 0.0-9.0 microg x mL(-1), the detection limit was 0.52 microg x mL(-1), and the correlation coeffient was 0.999 8. This method was simple, rapid, and selective. So its application to the determination of ribonucleic acid was satisfactory. The reaction mechanism was that the electrostatic interaction leads to molecular association of RNA with neutral red, resulting in anti-ion permutation and bonding reaction.

The Yersinia pestis gcvB gene encodes two small regulatory RNA molecules

PubMed Central

McArthur, Sarah D; Pulvermacher, Sarah C; Stauffer, George V

2006-01-01

Background In recent years it has become clear that small non-coding RNAs function as regulatory elements in bacterial virulence and bacterial stress responses. We tested for the presence of the small non-coding GcvB RNAs in Y. pestis as possible regulators of gene expression in this organism. Results In this study, we report that the Yersinia pestis KIM6 gcvB gene encodes two small RNAs. Transcription of gcvB is activated by the GcvA protein and repressed by the GcvR protein. The gcvB-encoded RNAs are required for repression of the Y. pestis dppA gene, encoding the periplasmic-binding protein component of the dipeptide transport system, showing that the GcvB RNAs have regulatory activity. A deletion of the gcvB gene from the Y. pestis KIM6 chromosome results in a decrease in the generation time of the organism as well as a change in colony morphology. Conclusion The results of this study indicate that the Y. pestis gcvB gene encodes two small non-coding regulatory RNAs that repress dppA expression. A gcvB deletion is pleiotropic, suggesting that the sRNAs are likely involved in controlling genes in addition to dppA. PMID:16768793

microRNA in Cerebral Spinal Fluid as Biomarkers of Alzheimer’s Disease Risk After Brain Injury

DTIC Science & Technology

2016-08-01

protein processing is a key feature of AD. MiRNAs are small non- coding RNA that regulate mRNA transcription, and may be a significant cause of protein...non- coding RNA that regulate mRNA transcription, and may be a significant cause of protein dysregulation. Our investigative team has generated

The effect of code expanding optimizations on instruction cache design

NASA Technical Reports Server (NTRS)

Chen, William Y.; Chang, Pohua P.; Conte, Thomas M.; Hwu, Wen-Mei W.

1991-01-01

It is shown that code expanding optimizations have strong and non-intuitive implications on instruction cache design. Three types of code expanding optimizations are studied: instruction placement, function inline expansion, and superscalar optimizations. Overall, instruction placement reduces the miss ratio of small caches. Function inline expansion improves the performance for small cache sizes, but degrades the performance of medium caches. Superscalar optimizations increases the cache size required for a given miss ratio. On the other hand, they also increase the sequentiality of instruction access so that a simple load-forward scheme effectively cancels the negative effects. Overall, it is shown that with load forwarding, the three types of code expanding optimizations jointly improve the performance of small caches and have little effect on large caches.

Chimeric peptide-mediated siRNA transduction to inhibit HIV-1 infection.

PubMed

Bivalkar-Mehla, Shalmali; Mehla, Rajeev; Chauhan, Ashok

2017-04-01

Persistent human immunodeficiency virus 1 (HIV-1) infection provokes immune activation and depletes CD4 +  lymphocytes, leading to acquired immunodeficiency syndrome. Uninterrupted administration of combination antiretroviral therapy (cART) in HIV-infected patients suppresses viral replication to below the detectable level and partially restores the immune system. However, cART-unresponsive residual HIV-1 infection and elusive transcriptionally silent but reactivatable viral reservoirs maintain a permanent viral DNA blue print. The virus rebounds within a few weeks after interruption of suppressive therapy. Adjunct gene therapy to control viral replication by ribonucleic acid interference (RNAi) is a post-transcriptional gene silencing strategy that could suppress residual HIV-1 burden and overcome viral resistance. Small interfering ribonucleic acids (siRNAs) are efficient transcriptional inhibitors, but need delivery systems to reach inside target cells. We investigated the potential of chimeric peptide (FP-PTD) to deliver specific siRNAs to HIV-1-susceptible and permissive cells. Chimeric FP-PTD peptide was designed with an RNA binding domain (PTD) to bind siRNA and a cell fusion peptide domain (FP) to enter cells. FP-PTD-siRNA complex entered and inhibited HIV-1 replication in susceptible cells, and could be a candidate for in vivo testing.

Selective inhibitors of trypanosomal uridylyl transferase RET1 establish druggability of RNA post-transcriptional modifications

PubMed Central

Cording, Amy; Gormally, Michael; Bond, Peter J.; Carrington, Mark; Balasubramanian, Shankar; Miska, Eric A.; Thomas, Beth

2017-01-01

ABSTRACT Non-coding RNAs are crucial regulators for a vast array of cellular processes and have been implicated in human disease. These biological processes represent a hitherto untapped resource in our fight against disease. In this work we identify small molecule inhibitors of a non-coding RNA uridylylation pathway. The TUTase family of enzymes is important for modulating non-coding RNA pathways in both human cancer and pathogen systems. We demonstrate that this new class of drug target can be accessed with traditional drug discovery techniques. Using the Trypanosoma brucei TUTase, RET1, we identify TUTase inhibitors and lay the groundwork for the use of this new target class as a therapeutic opportunity for the under-served disease area of African Trypanosomiasis. In a broader sense this work demonstrates the therapeutic potential for targeting RNA post-transcriptional modifications with small molecules in human disease. PMID:26786754

Selective inhibitors of trypanosomal uridylyl transferase RET1 establish druggability of RNA post-transcriptional modifications.

PubMed

Cording, Amy; Gormally, Michael; Bond, Peter J; Carrington, Mark; Balasubramanian, Shankar; Miska, Eric A; Thomas, Beth

2017-05-04

Non-coding RNAs are crucial regulators for a vast array of cellular processes and have been implicated in human disease. These biological processes represent a hitherto untapped resource in our fight against disease. In this work we identify small molecule inhibitors of a non-coding RNA uridylylation pathway. The TUTase family of enzymes is important for modulating non-coding RNA pathways in both human cancer and pathogen systems. We demonstrate that this new class of drug target can be accessed with traditional drug discovery techniques. Using the Trypanosoma brucei TUTase, RET1, we identify TUTase inhibitors and lay the groundwork for the use of this new target class as a therapeutic opportunity for the under-served disease area of African Trypanosomiasis. In a broader sense this work demonstrates the therapeutic potential for targeting RNA post-transcriptional modifications with small molecules in human disease.

Dual RNA regulatory control of a Staphylococcus aureus virulence factor.

PubMed

Chabelskaya, Svetlana; Bordeau, Valérie; Felden, Brice

2014-04-01

In pathogens, the accurate programming of virulence gene expression is essential for infection. It is achieved by sophisticated arrays of regulatory proteins and ribonucleic acids (sRNAs), but in many cases their contributions and connections are not yet known. Based on genetic, biochemical and structural evidence, we report that the expression pattern of a Staphylococcus aureus host immune evasion protein is enabled by the collaborative actions of RNAIII and small pathogenicity island RNA D (SprD). Their combined expression profiles during bacterial growth permit early and transient synthesis of Sbi to avoid host immune responses. Together, these two sRNAs use antisense mechanisms to monitor Sbi expression at the translational level. Deletion analysis combined with structural analysis of RNAIII in complex with its novel messenger RNA (mRNA) target indicate that three distant RNAIII domains interact with distinct sites of the sbi mRNA and that two locations are deep in the sbi coding region. Through distinct domains, RNAIII lowers production of two proteins required for avoiding innate host immunity, staphylococcal protein A and Sbi. Toeprints and in vivo mutational analysis reveal a novel regulatory module within RNAIII essential for attenuation of Sbi translation. The sophisticated translational control of mRNA by two differentially expressed sRNAs ensures supervision of host immune escape by a major pathogen.

MORPHOLOGICAL AND HISTOCHEMICAL CHANGES IN THE SPLEEN AND LYMPH NODE OF WHITE MICE IN RESPONSE TO RADIATION AND ANTIGENIC EFFECTS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akopova, V.A.

1961-01-01

Research was carried out on 90 white ntice subjected to x irradiation (Series I), vaccination with a brucellosis vaccine (Series II), and to a combined action of these factors (Series III and IV). The spleen and lymph nodes were studied both morphologically and histochemically. When exposing the mice to a total x-ray dose of 335 r, visible destructive changes and the lowering of desoxyribonucleic and ribonucleic acid level were found to occur in the spleen and lymph nodes. In the case of a single vaccination of the mice with the brucellosis vaccine, a certain vaccinal hyperplasia was observed in themore » spleen and lymph nodes, the level of desoxyribonucleic and ribonucleic acid being normal. In vaccinating the white mice, following total irradiation, destructive changes along with a gradual lowering of desoxyribonucleic and ribonucleic acid level are observed in the spleen and lymph nodes. The total x irradiation following a singie vaccination with the brucellosis vaccine, brings about slight destructive changes along with a simultaneous reticular hyperplasia in the spleen and lymph nodes. The levels of desoxyribonucleic and ribonucleic acids are high at all times. (auth)« less

Identification of microRNAs in the Toxigenic Dinoflagellate Alexandrium catenella by High-Throughput Illumina Sequencing and Bioinformatic Analysis

PubMed Central

Geng, Huili; Sui, Zhenghong; Zhang, Shu; Du, Qingwei; Ren, Yuanyuan; Liu, Yuan; Kong, Fanna; Zhong, Jie; Ma, Qingxia

2015-01-01

Micro-ribonucleic acids (miRNAs) are a large group of endogenous, tiny, non-coding RNAs consisting of 19–25 nucleotides that regulate gene expression at either the transcriptional or post-transcriptional level by mediating gene silencing in eukaryotes. They are considered to be important regulators that affect growth, development, and response to various stresses in plants. Alexandrium catenella is an important marine toxic phytoplankton species that can cause harmful algal blooms (HABs). To date, identification and function analysis of miRNAs in A. catenella remain largely unexamined. In this study, high-throughput sequencing was performed on A. catenella to identify and quantitatively profile the repertoire of small RNAs from two different growth phases. A total of 38,092,056 and 32,969,156 raw reads were obtained from the two small RNA libraries, respectively. In total, 88 mature miRNAs belonging to 32 miRNA families were identified. Significant differences were found in the member number, expression level of various families, and expression abundance of each member within a family. A total of 15 potentially novel miRNAs were identified. Comparative profiling showed that 12 known miRNAs exhibited differential expression between the lag phase and the logarithmic phase. Real-time quantitative RT-PCR (qPCR) was performed to confirm the expression of two differentially expressed miRNAs that were one up-regulated novel miRNA (aca-miR-3p-456915), and one down-regulated conserved miRNA (tae-miR159a). The expression trend of the qPCR assay was generally consistent with the deep sequencing result. Target predictions of the 12 differentially expressed miRNAs resulted in 1813target genes. Gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes pathway database (KEGG) annotations revealed that some miRNAs were associated with growth and developmental processes of the alga. These results provide insights into the roles that miRNAs play in the growth of A. catenella, and they provide the basis for further studies of the molecular mechanisms that underlie bloom growth in red tides species. PMID:26398216

Error Control Coding Techniques for Space and Satellite Communications

NASA Technical Reports Server (NTRS)

Costello, Daniel J., Jr.; Takeshita, Oscar Y.; Cabral, Hermano A.; He, Jiali; White, Gregory S.

1997-01-01

Turbo coding using iterative SOVA decoding and M-ary differentially coherent or non-coherent modulation can provide an effective coding modulation solution: (1) Energy efficient with relatively simple SOVA decoding and small packet lengths, depending on BEP required; (2) Low number of decoding iterations required; and (3) Robustness in fading with channel interleaving.

New basic approach to treat non-small cell lung cancer based on RNA-interference.

PubMed

Makowiecki, Christina; Nolte, Andrea; Sutaj, Besmire; Keller, Timea; Avci-Adali, Meltem; Stoll, Heidi; Schlensak, Christian; Wendel, Hans Peter; Walker, Tobias

2014-03-01

To date the therapy for non-small cell lung cancer (NSCLC) is associated with severe side effects, frustrating outcomes, and does not consider different tumor characteristics. The RNA-interference (RNAi) pathway represents a potential new approach to treat NSCLC. With small interfering ribonucleic acids (siRNAs), it is possible to reduce the expression of proliferation-dependent proteins in tumor cells, leading to their apoptosis. We propose that siRNAs could be adapted to the tumor type and may cause fewer side effects than current therapy. Four NSCLC cell lines were cultured under standard conditions and transfected with three different concentrations of siRNAs targeted against the hypoxia-inducible factors 1α and 2α (HIF1α and HIF2α) and signal transducer and activator of transcription 3 (STAT3). The expression was observed by quantitative real-time polymerase chain reaction and western blots. For the analysis of cell growth three days after transfection, the cell number was detected using a CASY cell counter system. The results of the silencing of the analyzed factors differ in each cell line. Cell growth was significantly reduced in all cell lines after transfection with HIF1α- and STAT3-siRNA. The silencing of HIF2α resulted in a significant effect on cell growth in squamous, and large-cell lung cancer. This study shows that the knockdown and viability to siRNA transfection differ in each tumor type according to the used siRNA. This implies that the tumor types differ among themselves and should be treated differently. Therefore, the authors suggest a possible approach to a more personalized treatment of NSCLC.

Early Clinical Diagnosis of PC1/3 Deficiency in a Patient With a Novel Homozygous PCSK1 Splice-Site Mutation.

PubMed

Härter, Bettina; Fuchs, Irene; Müller, Thomas; Akbulut, Ulas Emre; Cakir, Murat; Janecke, Andreas R

2016-04-01

Autosomal recessive proprotein convertase 1/3 (PC1/3) deficiency, caused by mutations in the PCSK1 gene, is characterized by severe congenital malabsorptive diarrhea, early-onset obesity, and certain endocrine abnormalities. We suspected PC1/3 deficiency in a 4-month-old girl based on the presence of congenital diarrhea and polyuria. Sequencing the whole coding region and splice sites detected a novel homozygous PCSK1 splice-site mutation, c.544-2A>G, in the patient. The mutation resulted in the skipping of exon 5, the generation of a premature termination codon, and nonsense-mediated PCSK1 messenger ribonucleic acid decay, which was demonstrated in complementary DNA derived from fibroblasts.

Cis-encoded non-coding antisense RNAs in streptococci and other low GC Gram (+) bacterial pathogens

PubMed Central

Cho, Kyu Hong; Kim, Jeong-Ho

2015-01-01

Due to recent advances of bioinformatics and high throughput sequencing technology, discovery of regulatory non-coding RNAs in bacteria has been increased to a great extent. Based on this bandwagon, many studies searching for trans-acting small non-coding RNAs in streptococci have been performed intensively, especially in the important human pathogen, group A and B streptococci. However, studies for cis-encoded non-coding antisense RNAs in streptococci have been scarce. A recent study shows antisense RNAs are involved in virulence gene regulation in group B streptococcus, S. agalactiae. This suggests antisense RNAs could have important roles in the pathogenesis of streptococcal pathogens. In this review, we describe recent discoveries of chromosomal cis-encoded antisense RNAs in streptococcal pathogens and other low GC Gram (+) bacteria to provide a guide for future studies. PMID:25859258

Cloning, Characterization, and Expression of Animal Toxin Genes for Vaccine Development

DTIC Science & Technology

1990-04-27

amino acids have been modified to pyroglutamate . The function of this modification is not known. There are additional venom components that are...been constructed from the messenger ribonucleic acid (mRNA) isolated from venom glands of different poisonous animals such as snakes, scorpions, and...ribonucleic acid (mRNA) isolated from venom glands of different poisonous animals such as snakes, scorpions, and snails. The gene banks thus created con

Ultrasound-microbubble-mediated intercellular adhesion molecule-1 small interfering ribonucleic acid transfection attenuates neointimal formation after arterial injury in mice.

PubMed

Suzuki, Jun-ichi; Ogawa, Masahito; Takayama, Kiyoshi; Taniyama, Yoshiaki; Morishita, Ryuichi; Hirata, Yasunobu; Nagai, Ryozo; Isobe, Mitsuaki

2010-03-02

The purpose of this study was to investigate the efficiency of small interfering ribonucleic acid (siRNA) in murine arteries. We transfected it using a nonviral ultrasound-microbubble-mediated in vivo gene delivery system. siRNA is an effective methodology to suppress gene function. The siRNA can be synthesized easily; however, a major obstacle in the use of siRNA as therapeutics is the difficulty involved in effective in vivo delivery. To investigate the efficiency of nonviral ultrasound-microbubble-mediated in vivo siRNA delivery, we used a fluorescein-labeled siRNA, green fluorescent protein (GFP) siRNA, and intercellular adhesion molecule (ICAM)-1 siRNA in murine arteries. Murine femoral arteries were injured using flexible wires to establish arterial injury. The fluorescein-labeled siRNA and GFP siRNA showed that this nonviral approach could deliver siRNA into target arteries effectively without any tissue damage and systemic adverse effects. ICAM-1 siRNA transfection into murine injured arteries significantly suppressed the development of neointimal formation in comparison to those in the control group. Immunohistochemistry revealed that accumulation of T cells and adhesion molecule positive cells was observed in nontreated injured arteries, whereas siRNA suppressed accumulation. The nonviral ultrasound-microbubble delivery of siRNA ensures effective transfection into target arteries. ICAM-1 siRNA has the potential to suppress arterial neointimal formation. Transfection of siRNA can be beneficial for the clinical treatment of cardiovascular and other inflammatory diseases. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities.

PubMed

Chang, Wenguang

2017-01-15

Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D. Previous studies have primarily focused on a diverse array of efficacy end points of berberine in the pathogenesis of metabolic syndromes and inflammation or oxidative stress. Currently, an increasing number of studies have revealed the importance of non-coding RNAs as regulators of the anti-diabetic effects of berberine. The regulation of non-coding RNAs has been associated with several therapeutic actions of berberine in T2D progression. Thus, this review summarizes the anti-diabetic mechanisms of berberine by focusing on its role in regulating non-coding RNA, thus demonstrating that berberine exerts global anti-diabetic effects by targeting non-coding RNAs and that these effects involve several miRNAs, lncRNAs and multiple signal pathways, which may enhance the current understanding of the anti-diabetic mechanism actions of berberine and provide new pathological targets for the development of berberine-related drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment.

PubMed

Mills, James D; Iyer, Anand M; van Scheppingen, Jackelien; Bongaarts, Anika; Anink, Jasper J; Janssen, Bart; Zimmer, Till S; Spliet, Wim G; van Rijen, Peter C; Jansen, Floor E; Feucht, Martha; Hainfellner, Johannes A; Krsek, Pavel; Zamecnik, Josef; Kotulska, Katarzyna; Jozwiak, Sergiusz; Jansen, Anna; Lagae, Lieven; Curatolo, Paolo; Kwiatkowski, David J; Pasterkamp, R Jeroen; Senthilkumar, Ketharini; von Oerthel, Lars; Hoekman, Marco F; Gorter, Jan A; Crino, Peter B; Mühlebner, Angelika; Scicluna, Brendon P; Aronica, Eleonora

2017-08-14

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network. Overall we detected 438 differentially expressed genes and 991 differentially expressed small non-coding RNAs in cortical tubers compared to autopsy control brain tissue. We observed increased expression of genes associated with inflammatory, innate and adaptive immune responses. In contrast, we observed a down-regulation of genes associated with neurogenesis and glutamate receptor signaling. MicroRNAs represented the largest class of over-expressed small non-coding RNA species in tubers. In particular, our analysis revealed that the miR-34 family (including miR-34a, miR-34b and miR-34c) was significantly over-expressed. Functional studies demonstrated the ability of miR-34b to modulate neurite outgrowth in mouse primary hippocampal neuronal cultures. This study provides new insights into the TSC transcriptomic network along with the identification of potential new treatment targets.

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA.

PubMed

Li, Siqi; Xu, Zhengping; Sheng, Jinghao

2018-05-10

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

Comparison of Two Serologically Distinct Ribonucleic Acid Bacteriophages I. Properties of the Viral Particles

PubMed Central

Overby, L. R.; Barlow, G. H.; Doi, R. H.; Jacob, Monique; Spiegelman, S.

1966-01-01

Overby, L. R. (University of Illinois, Urbana), G. H. Barlow, R. H. Doi, Monique Jacob, and S. Spiegelman. Comparison of two serologically distinct ribonucleic acid bacteriophages. I. Properties of the viral particle. J. Bacteriol. 91:442–448. 1966.—Two ribonucleic acid (RNA) coliphages, MS-2 and Qβ, have been characterized physically and serologically. MS-2 has an S20, w value of 79, a molecular weight of 3.6 × 106, a density of 1.422, and pH 3.9 as its isoelectric point. Qβ has an S20, w of 84, a molecular weight of 4.2 × 106, a density of 1.439, and an isoelectric point at pH 5.3. One host (Escherichia coli A-19) permits a distinction between the two on the basis of a marked difference in plaque size. They are distinct immunochemically, no serological cross-reaction being detectable. Images PMID:5903109

Effect of Thymine Starvation on Messenger Ribonucleic Acid Synthesis in Escherichia coli

PubMed Central

Luzzati, Denise

1966-01-01

Luzzati, Denise (Institut de Biologie Physico-Chimique, Paris, France). Effect of thymine starvation on messenger ribonucleic acid synthesis in Escherichia coli. J. Bacteriol. 92:1435–1446. 1966.—During the course of thymine starvation, the rate of synthesis of messenger ribonucleic acid (mRNA, the rapidly labeled fraction of the RNA which decays in the presence of dinitrophenol or which hybridizes with deoxyribonucleic acid) decreases exponentially, in parallel with the viability of the thymine-starved bacteria. The ability of cell-free extracts of starved bacteria to incorporate ribonucleoside triphosphates into RNA was determined; it was found to be inferior to that of extracts from control cells. The analysis of the properties of cell-free extracts of starved cells shows that their decreased RNA polymerase activity is the consequence of a modification of their deoxyribonucleic acid, the ability of which to serve as a template for RNA polymerase decreases during starvation. PMID:5332402

In Vitro Product of a Ribonucleic Acid Polymerase Induced by Influenza Virus

PubMed Central

Mahy, B. W. J.; Bromley, P. A.

1970-01-01

The ribonucleic acid (RNA)-dependent RNA polymerase induced in the microsomal fraction of cells infected with influenza virus synthesized a mixture of single-and double-stranded RNA in vitro. The single-stranded RNA sedimented mainly in the 8S region on sucrose density gradients, with a smaller proportion of the RNA sedimenting at 18S. This sedimentation pattern corresponds closely to that of incomplete influenza virus RNA. The double-stranded RNA formed in vitro sedimented at 11S, but molecules which may be replicative intermediate, sedimenting at 14 to 20S, were also detected in the in vitro reaction product. Similar species of RNA were detected in vivo by pulse-labeling infected cells at the time of polymerase harvest, but the proportion of each RNA species was different, most of the RNA being single-stranded and sedimenting in the 18S region. An 11S double-stranded RNA was also synthesized in vivo. Pulse chase analysis of the double-stranded RNA synthesized in vitro showed that most is stable, and only a small proportion turns over during the reaction. A proportion of the RNA formed in vitro could be annealed to RNA formed in infected cells and to RNA extracted from purified virus. PMID:5480408

Differential expression and emerging functions of non-coding RNAs in cold adaptation.

PubMed

Frigault, Jacques J; Morin, Mathieu D; Morin, Pier Jr

2017-01-01

Several species undergo substantial physiological and biochemical changes to confront the harsh conditions associated with winter. Small mammalian hibernators and cold-hardy insects are examples of natural models of cold adaptation that have been amply explored. While the molecular picture associated with cold adaptation has started to become clearer in recent years, notably through the use of high-throughput experimental approaches, the underlying cold-associated functions attributed to several non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), remain to be better characterized. Nevertheless, key pioneering work has provided clues on the likely relevance of these molecules in cold adaptation. With an emphasis on mammalian hibernation and insect cold hardiness, this work first reviews various molecular changes documented so far in these processes. The cascades leading to miRNA and lncRNA production as well as the mechanisms of action of these non-coding RNAs are subsequently described. Finally, we present examples of differentially expressed non-coding RNAs in models of cold adaptation and elaborate on the potential significance of this modulation with respect to low-temperature adaptation.

Identification of novel non-coding small RNAs from Streptococcus pneumoniae TIGR4 using high-resolution genome tiling arrays

PubMed Central

2010-01-01

Background The identification of non-coding transcripts in human, mouse, and Escherichia coli has revealed their widespread occurrence and functional importance in both eukaryotic and prokaryotic life. In prokaryotes, studies have shown that non-coding transcripts participate in a broad range of cellular functions like gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Streptococcus pneumoniae (pneumococcus), an obligate human respiratory pathogen responsible for significant worldwide morbidity and mortality. Tiling microarrays enable genome wide mRNA profiling as well as identification of novel transcripts at a high-resolution. Results Here, we describe a high-resolution transcription map of the S. pneumoniae clinical isolate TIGR4 using genomic tiling arrays. Our results indicate that approximately 66% of the genome is expressed under our experimental conditions. We identified a total of 50 non-coding small RNAs (sRNAs) from the intergenic regions, of which 36 had no predicted function. Half of the identified sRNA sequences were found to be unique to S. pneumoniae genome. We identified eight overrepresented sequence motifs among sRNA sequences that correspond to sRNAs in different functional categories. Tiling arrays also identified approximately 202 operon structures in the genome. Conclusions In summary, the pneumococcal operon structures and novel sRNAs identified in this study enhance our understanding of the complexity and extent of the pneumococcal 'expressed' genome. Furthermore, the results of this study open up new avenues of research for understanding the complex RNA regulatory network governing S. pneumoniae physiology and virulence. PMID:20525227

Structures Containing Polyphosphate in Micrococcus lysodeikticus1

PubMed Central

Friedberg, Ilan; Avigad, Gad

1968-01-01

Granular structures containing inorganic polyphosphate were found in Micrococcus lysodeikticus. These structures were isolated by fractionation of the bacterial extract obtained by lysing the organisms with lysozyme. The composition of the fraction which was enriched with these structures was found to be: protein, 24%; lipids, 30%; and polyphosphate, 27%. This fraction also contained small amounts of ribonucleic acids, carbohydrate, and polyvalent cations. The effect of different reagents and enzymes on the integrity of the granules was examined. It was noticed that they accumulate in the bacteria during the logarithmic phase of growth but disappear gradually during the stationary phase. Images PMID:5674060

Synergistic Effect of Auto-Activation and Small RNA Regulation on Gene Expression

NASA Astrophysics Data System (ADS)

Xiong, Li-Ping; Ma, Yu-Qiang; Tang, Lei-Han

2010-09-01

Auto-activation and small ribonucleic acid (RNA)-mediated regulation are two important mechanisms in controlling gene expression. We study the synergistic effect of these two regulations on gene expression. It is found that under this combinatorial regulation, gene expression exhibits bistable behaviors at the transition regime, while each of these two regulations, if working solely, only leads to monostability. Within the stochastic framework, the base pairing strength between sRNA and mRNA plays an important role in controlling the transition time between on and off states. The noise strength of protein number in the off state approaches 1 and is smaller than that in the on state. The noise strength also depends on which parameters, the feedback strength or the synthesis rate of small RNA, are tuned in switching the gene expression on and off. Our findings may provide a new insight into gene-regulation mechanism and can be applied in synthetic biology.

Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events

PubMed Central

Ashouri, Arghavan; Sayin, Volkan I.; Van den Eynden, Jimmy; Singh, Simranjit X.; Papagiannakopoulos, Thales; Larsson, Erik

2016-01-01

Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here we make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Our screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways. The associations are often highly reproducible across cancer types, and while many lncRNAs are co-expressed with their protein-coding hosts or neighbours, some are intergenic and independent. We highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. Our study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers. PMID:28959951

Evidence for the absence of the terminal adenine nucleotide at the amino acid-acceptor end of transfer ribonucleic acid in non-lactating bovine mammary gland and its inhibitory effect on the aminoacylation of rat liver transfer ribonucleic acid

PubMed Central

Herrington, M. D.; Hawtrey, A. O.

1970-01-01

1. tRNA isolated from non-lactating bovine mammary gland competitively inhibits the formation of aminoacyl-tRNA in the rat liver system. 2. Non-lactating bovine mammary gland tRNA and twice-pyrophosphorolysed rat liver tRNA are unable to accept amino acids in a reaction catalysed by aminoacyl-tRNA synthetases from either rat liver or bovine mammary gland. Deacylated rat liver tRNA can however be aminoacylated in the presence of either enzyme. 3. Bovine mammary gland tRNA lacks the terminal adenine nucleotide at the 3′-terminus amino acid acceptor end, which can be replaced by incubation in the presence of rat liver nucleotide-incorporating enzyme, ATP and CTP. 4. The enzymically modified bovine tRNA (tRNApCpCpA) can bind labelled amino acids to form aminoacyl-tRNA, which can then transfer its labelled amino acids to growing polypeptide chains on ribosomes. 5. Molecules of rat liver tRNA or bovine mammary gland tRNA that lack the terminal adenine nucleotide or the terminal cytosine and adenine nucleotides inhibit the aminoacylation of normal rat liver tRNA to varying degrees. tRNA molecules lacking the terminal −pCpCpA nucleotide sequence exhibit the major inhibitory effect. 6. The enzyme fraction from bovine mammary gland corresponding to that containing the nucleotide-incorporating enzyme in rat liver is unable to catalyse the incorporation of cytosine and adenine nucleotides in pyrophosphorolysed rat liver tRNA and deacylated bovine tRNA. This fraction also markedly inhibits the action of the rat liver nucleotide-incorporating enzyme. PMID:5435687

Molecular mimicry between protein and tRNA.

PubMed

Nakamura, Y

2001-01-01

Mimicry is a sophisticated development in animals, fish, and plants that allows them to fool others by imitating a shape or color for diverse purposes, such as to prey, evade, lure, pollinate, or threaten. This is not restricted to the macro-world, but extends to the micro-world as molecular mimicry. Recent advances in structural and molecular biology uncovered a set of translation factors that resembles a tRNA shape and, in one case, even mimics a tRNA function for deciphering the genetic code. Nature must have evolved this art of molecular mimicry between protein and ribonucleic acid by using different protein structures until the translation factors sat in the cockpit of a ribosome machine, on behalf of tRNA, and achieved diverse actions. Structural, functional, and evolutionary aspects of molecular mimicry will be discussed.

48 CFR 1352.213-71 - Instructions for submitting quotations under the simplified acquisition threshold-non-commercial.

Code of Federal Regulations, 2010 CFR

2010-10-01

... submitting quotations under the simplified acquisition threshold-non-commercial. 1352.213-71 Section 1352.213... quotations under the simplified acquisition threshold—non-commercial. As prescribed in 48 CFR 1313.302-1-70... Threshold—Non-Commercial (APR 2010) (a) North American Industry Classification System (NAICS) code and small...

Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective

PubMed Central

Martínez-Chavarría, Luary C.; Vadyvaloo, Viveka

2015-01-01

Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens. PMID:26441890

Influence of the stringent control system on the transcription of ribosomal ribonucleic acid and ribosomal protein genes in Escherichia coli.

PubMed Central

Dennis, P P

1977-01-01

The fraction of the total ribonucleic acid (RNA) synthesis rate that is messenger RNA (mRNA) for ribosomal protein (r-protein) and ribosomal RNA (rRNA) has been estimated in valS(Ts) rel+ stringent and valS(Ts) relA1 relaxed strains of Escherichia coli during a partial inhibition of valyl-transfer RNA aminoacylation. The partial inhibition was accomplished by shifting the strains from the permissive growth temperature of 29.5 degrees C to the semipermissive temperature of 35.5 degrees C. The RNA synthesized at the elevated temperature was pulse labeled with [3H]uracil. The fraction of the total incorpoarted 3H radioactivity in r-protein mRNA or in rRNA was estimated by specific hybridization to the transducing phages gammaspc1, which carries about 15 r-protein genes and lambdailv5, which carries an rRNA transcription unit. The results clearly demonstrate that the rel gene influences the fraction of the total RNA synthesis rate that is r protein mRNA and rRNA; in the rel+ strain they are significantly increased relative to control cultures. This indicates that the expression of the genes coding for the RNA and protein component of the ribosome are most likely regulated at the level of transcription. Furthermore, it appears that the distribution of functioning RNA polymerase between rRNA genes, r-protein genes, and other types of genes is influenced by the rel gene control system; presumably this influence is mediated through the unusual nucleotide guanosine tetraphosphate. PMID:320185

Identification of differentially expressed small non-coding RNAs in the legume endosymbiont Sinorhizobium meliloti by comparative genomics

PubMed Central

del Val, Coral; Rivas, Elena; Torres-Quesada, Omar; Toro, Nicolás; Jiménez-Zurdo, José I

2007-01-01

Bacterial small non-coding RNAs (sRNAs) are being recognized as novel widespread regulators of gene expression in response to environmental signals. Here, we present the first search for sRNA-encoding genes in the nitrogen-fixing endosymbiont Sinorhizobium meliloti, performed by a genome-wide computational analysis of its intergenic regions. Comparative sequence data from eight related α-proteobacteria were obtained, and the interspecies pairwise alignments were scored with the programs eQRNA and RNAz as complementary predictive tools to identify conserved and stable secondary structures corresponding to putative non-coding RNAs. Northern experiments confirmed that eight of the predicted loci, selected among the original 32 candidates as most probable sRNA genes, expressed small transcripts. This result supports the combined use of eQRNA and RNAz as a robust strategy to identify novel sRNAs in bacteria. Furthermore, seven of the transcripts accumulated differentially in free-living and symbiotic conditions. Experimental mapping of the 5′-ends of the detected transcripts revealed that their encoding genes are organized in autonomous transcription units with recognizable promoter and, in most cases, termination signatures. These findings suggest novel regulatory functions for sRNAs related to the interactions of α-proteobacteria with their eukaryotic hosts. PMID:17971083

Prevalence and molecular characterization of Cryptosporidium spp. and Giardia duodenalis in deer in Henan and Jilin, China.

PubMed

Huang, Jianying; Zhang, Zhenjie; Zhang, Yiqi; Yang, Yong; Zhao, Jinfeng; Wang, Rongjun; Jian, Fuchun; Ning, Changshen; Zhang, Wanyu; Zhang, Longxian

2018-04-12

Little is known about the prevalence and zoonotic potential of Cryptosporidium spp. and Giardia duodenalis in deer in China. In this study, 662 fecal samples were collected from 11 farms in Henan and Jilin Provinces between July 2013 and August 2014, and were screened for the presence of Cryptosporidium and G. duodenalis with genotyping and subtyping methods. Cryptosporidium spp. and G. duodenalis were detected in 6.80% (45/662) and 1.21% (5/662) of samples, respectively. Six Cryptosporidium species/genotypes were identified based on the small subunit ribosomal ribonucleic acid (SSU rRNA) gene: C. parvum (n = 11); C. andersoni (n = 5); C. ubiquitum (n = 3); C. muris (n = 1); C. suis-like (n = 1); and Cryptosporidium deer genotype (n = 24). When five of the 11 C. parvum isolates were subtyped by sequencing the 60 kDa glycoprotein (gp60) gene, zoonotic subtypes IIaA15G2R2 (n = 4) and IIdA19G1 (n = 1) were found. According to a subtype analysis, three C. ubiquitum isolates belonged to XIIa subtype 2. In contrast, only assemblage E was detected in the five Giardia-positive samples with small subunit ribosomal ribonucleic acid (SSU rRNA) gene sequencing. To our knowledge, this is the first study to report C. andersoni, as well as C. parvum zoonotic subtypes IIaA15G2R2 and IIdA19G1 in cervids. These data, though limited, suggest that cervids may be a source of zoonotic Cryptosporidium and Giardia. Cervids in the present study are likely to be of low zoonotic potential to humans, and more molecular epidemiological studies are required to clarify the prevalence and public health significance of Cryptosporidium and G. duodenalis in cervids throughout China.

AX-GADGET: a new code for cosmological simulations of Fuzzy Dark Matter and Axion models

NASA Astrophysics Data System (ADS)

Nori, Matteo; Baldi, Marco

2018-05-01

We present a new module of the parallel N-Body code P-GADGET3 for cosmological simulations of light bosonic non-thermal dark matter, often referred as Fuzzy Dark Matter (FDM). The dynamics of the FDM features a highly non-linear Quantum Potential (QP) that suppresses the growth of structures at small scales. Most of the previous attempts of FDM simulations either evolved suppressed initial conditions, completely neglecting the dynamical effects of QP throughout cosmic evolution, or resorted to numerically challenging full-wave solvers. The code provides an interesting alternative, following the FDM evolution without impairing the overall performance. This is done by computing the QP acceleration through the Smoothed Particle Hydrodynamics (SPH) routines, with improved schemes to ensure precise and stable derivatives. As an extension of the P-GADGET3 code, it inherits all the additional physics modules implemented up to date, opening a wide range of possibilities to constrain FDM models and explore its degeneracies with other physical phenomena. Simulations are compared with analytical predictions and results of other codes, validating the QP as a crucial player in structure formation at small scales.

Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans

PubMed Central

Kowalski, Madzia P.; Baylis, Howard A.; Krude, Torsten

2015-01-01

ABSTRACT Stem bulge RNAs (sbRNAs) are a family of small non-coding stem-loop RNAs present in Caenorhabditis elegans and other nematodes, the function of which is unknown. Here, we report the first functional characterisation of nematode sbRNAs. We demonstrate that sbRNAs from a range of nematode species are able to reconstitute the initiation of chromosomal DNA replication in the presence of replication proteins in vitro, and that conserved nucleotide sequence motifs are essential for this function. By functionally inactivating sbRNAs with antisense morpholino oligonucleotides, we show that sbRNAs are required for S phase progression, early embryonic development and the viability of C. elegans in vivo. Thus, we demonstrate a new and essential role for sbRNAs during the early development of C. elegans. sbRNAs show limited nucleotide sequence similarity to vertebrate Y RNAs, which are also essential for the initiation of DNA replication. Our results therefore establish that the essential function of small non-coding stem-loop RNAs during DNA replication extends beyond vertebrates. PMID:25908866

RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336”

PubMed Central

Kumar, Ranjit; Lawrence, Mark L.; Watt, James; Cooksey, Amanda M.; Burgess, Shane C.; Nanduri, Bindu

2012-01-01

Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis. Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs). Whole genome transcriptome analysis is a complementary method to identify “novel” genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis. In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method. The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies. We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation. The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome. When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome). This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations. PMID:22276113

RNA-seq based transcriptional map of bovine respiratory disease pathogen "Histophilus somni 2336".

PubMed

Kumar, Ranjit; Lawrence, Mark L; Watt, James; Cooksey, Amanda M; Burgess, Shane C; Nanduri, Bindu

2012-01-01

Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis. Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs). Whole genome transcriptome analysis is a complementary method to identify "novel" genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis. In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method.The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies. We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation. The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome. When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome). This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations.

SHARAKU: an algorithm for aligning and clustering read mapping profiles of deep sequencing in non-coding RNA processing.

PubMed

Tsuchiya, Mariko; Amano, Kojiro; Abe, Masaya; Seki, Misato; Hase, Sumitaka; Sato, Kengo; Sakakibara, Yasubumi

2016-06-15

Deep sequencing of the transcripts of regulatory non-coding RNA generates footprints of post-transcriptional processes. After obtaining sequence reads, the short reads are mapped to a reference genome, and specific mapping patterns can be detected called read mapping profiles, which are distinct from random non-functional degradation patterns. These patterns reflect the maturation processes that lead to the production of shorter RNA sequences. Recent next-generation sequencing studies have revealed not only the typical maturation process of miRNAs but also the various processing mechanisms of small RNAs derived from tRNAs and snoRNAs. We developed an algorithm termed SHARAKU to align two read mapping profiles of next-generation sequencing outputs for non-coding RNAs. In contrast with previous work, SHARAKU incorporates the primary and secondary sequence structures into an alignment of read mapping profiles to allow for the detection of common processing patterns. Using a benchmark simulated dataset, SHARAKU exhibited superior performance to previous methods for correctly clustering the read mapping profiles with respect to 5'-end processing and 3'-end processing from degradation patterns and in detecting similar processing patterns in deriving the shorter RNAs. Further, using experimental data of small RNA sequencing for the common marmoset brain, SHARAKU succeeded in identifying the significant clusters of read mapping profiles for similar processing patterns of small derived RNA families expressed in the brain. The source code of our program SHARAKU is available at http://www.dna.bio.keio.ac.jp/sharaku/, and the simulated dataset used in this work is available at the same link. Accession code: The sequence data from the whole RNA transcripts in the hippocampus of the left brain used in this work is available from the DNA DataBank of Japan (DDBJ) Sequence Read Archive (DRA) under the accession number DRA004502. yasu@bio.keio.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Non-linear hydrodynamical evolution of rotating relativistic stars: numerical methods and code tests

NASA Astrophysics Data System (ADS)

Font, José A.; Stergioulas, Nikolaos; Kokkotas, Kostas D.

2000-04-01

We present numerical hydrodynamical evolutions of rapidly rotating relativistic stars, using an axisymmetric, non-linear relativistic hydrodynamics code. We use four different high-resolution shock-capturing (HRSC) finite-difference schemes (based on approximate Riemann solvers) and compare their accuracy in preserving uniformly rotating stationary initial configurations in long-term evolutions. Among these four schemes, we find that the third-order piecewise parabolic method scheme is superior in maintaining the initial rotation law in long-term evolutions, especially near the surface of the star. It is further shown that HRSC schemes are suitable for the evolution of perturbed neutron stars and for the accurate identification (via Fourier transforms) of normal modes of oscillation. This is demonstrated for radial and quadrupolar pulsations in the non-rotating limit, where we find good agreement with frequencies obtained with a linear perturbation code. The code can be used for studying small-amplitude or non-linear pulsations of differentially rotating neutron stars, while our present results serve as testbed computations for three-dimensional general-relativistic evolution codes.

Analysis of Isoaccepting Transfer Ribonucleic Acid Species of Bacillus subtilis: Chromatographic Differences Between Transfer Ribonucleic Acids from Spores and Cells in Exponential Growth

PubMed Central

Vold, Barbara S.

1973-01-01

Differences between the transfer ribonucleic acid (tRNA) of spores and exponentially growing cells of Bacillus subtilis 168 were compared by co-chromatography on reversed-phase column RPC-5. This system gave excellent resolution of isoaccepting species in 1 to 2 hr using a 200-ml gradient. Two methods were used to extract spore tRNAs, a procedure using a Braun homogenizer and a pretreatment with dithiothreitol followed by lysis with lysozyme. Where changes were observed, column elution profiles of spore tRNAs were independent of the extraction method used. Three kinds of changes between the profiles of vegetative cell tRNA and spore tRNA were observed: (i) no change; phe-, val-, ala-, asp-, ileu-, pro-, met-, fmet-, and his-tRNAs, (ii) a change in the ratio of existing peaks; gly-, tyr-, leu-, ser-, thr-, aspn-, and arg-tRNAs, and (iii) the appearance or disappearance of unique peaks; lys-, glu-, and trp-tRNAs. PMID:4632322

Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

PubMed

Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

2014-10-01

This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

76 FR 76205 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change Relating...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... relating to codes of ethics. This Rule requires investment advisers to adopt a code of ethics that reflects... securities laws. Accordingly, procedures designed to prevent the communication and misuse of non-public... securities of large, medium and small capitalization companies across the globe including developed countries...

RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines.

PubMed

Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, Marialucia; Raggi, Chiara; Gissi, Clarissa; D'Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C

2017-10-10

Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell lines: HuH7, Hep3B, HepG2 (hepato-cellular carcinoma) and HuH6 (hepatoblastoma), generating two different sets of sequencing libraries for each. One library was size-selected for small RNAs and the other targeted the whole transcriptome. Here are reported genome wide data of the expression level of coding and non-coding transcripts, microRNAs, isomiRs and snoRNAs providing the first comprehensive overview of the extracellular-vesicle RNA cargo released from LC cell lines. The EV-RNA expression profiles of the four liver cancer cell lines share a similar background, but cell-specific features clearly emerge showing the marked heterogeneity of the EV-cargo among the individual cell lines, evident both for the coding and non-coding RNA species.

Quantitative Profiling of Peptides from RNAs classified as non-coding

PubMed Central

Prabakaran, Sudhakaran; Hemberg, Martin; Chauhan, Ruchi; Winter, Dominic; Tweedie-Cullen, Ry Y.; Dittrich, Christian; Hong, Elizabeth; Gunawardena, Jeremy; Steen, Hanno; Kreiman, Gabriel; Steen, Judith A.

2014-01-01

Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences - including introns and several classes of non-coding RNAs (ncRNAs) do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here, we use computational methods to identify the products of non-canonical translation in mouse neurons by analyzing unannotated transcripts in combination with proteomic data. This study supports the existence of non-canonical translation products from both intragenic and extragenic genomic regions, including peptides derived from anti-sense transcripts and introns. Moreover, the studied novel translation products exhibit temporal regulation similar to that of proteins known to be involved in neuronal activity processes. These observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential. PMID:25403355

Detection of non-coding RNA in bacteria and archaea using the DETR'PROK Galaxy pipeline.

PubMed

Toffano-Nioche, Claire; Luo, Yufei; Kuchly, Claire; Wallon, Claire; Steinbach, Delphine; Zytnicki, Matthias; Jacq, Annick; Gautheret, Daniel

2013-09-01

RNA-seq experiments are now routinely used for the large scale sequencing of transcripts. In bacteria or archaea, such deep sequencing experiments typically produce 10-50 million fragments that cover most of the genome, including intergenic regions. In this context, the precise delineation of the non-coding elements is challenging. Non-coding elements include untranslated regions (UTRs) of mRNAs, independent small RNA genes (sRNAs) and transcripts produced from the antisense strand of genes (asRNA). Here we present a computational pipeline (DETR'PROK: detection of ncRNAs in prokaryotes) based on the Galaxy framework that takes as input a mapping of deep sequencing reads and performs successive steps of clustering, comparison with existing annotation and identification of transcribed non-coding fragments classified into putative 5' UTRs, sRNAs and asRNAs. We provide a step-by-step description of the protocol using real-life example data sets from Vibrio splendidus and Escherichia coli. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Decoding the Emerging Patterns Exhibited in Non-coding RNAs Characteristic of Lung Cancer with Regard to their Clinical Significance.

PubMed

Sonea, Laura; Buse, Mihail; Gulei, Diana; Onaciu, Anca; Simon, Ioan; Braicu, Cornelia; Berindan-Neagoe, Ioana

2018-05-01

Lung cancer continues to be the leading topic concerning global mortality rate caused by can-cer; it needs to be further investigated to reduce these dramatic unfavorable statistic data. Non-coding RNAs (ncRNAs) have been shown to be important cellular regulatory factors and the alteration of their expression levels has become correlated to extensive number of pathologies. Specifically, their expres-sion profiles are correlated with development and progression of lung cancer, generating great interest for further investigation. This review focuses on the complex role of non-coding RNAs, namely miR-NAs, piwi-interacting RNAs, small nucleolar RNAs, long non-coding RNAs and circular RNAs in the process of developing novel biomarkers for diagnostic and prognostic factors that can then be utilized for personalized therapies toward this devastating disease. To support the concept of personalized medi-cine, we will focus on the roles of miRNAs in lung cancer tumorigenesis, their use as diagnostic and prognostic biomarkers and their application for patient therapy.

Identification of small non-coding RNA classes expressed in swine whole blood during HP-PRRSV infection.

PubMed

Fleming, Damarius S; Miller, Laura C

2018-04-01

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs have emerged as having an important role in the immune system in humans. The study uses transcriptomic read counts to profile the type and quantity of both well and lesser characterized sncRNAs, such as microRNAs and small nucleolar RNAs to identify and quantify the classes of sncRNA expressed in whole blood between healthy and highly pathogenic PRRSV-infected pigs. Our results returned evidence on nine classes of sncRNA, four of which were consistently statistically significantly different based on Fisher's Exact Test, that can be detected and possibly interrogated for their effect on host dysregulation during PRRSV infections. Published by Elsevier Inc.

The complete mitochondrial genome of Rapana venosa (Gastropoda, Muricidae).

PubMed

Sun, Xiujun; Yang, Aiguo

2016-01-01

The complete mitochondrial (mt) genome of the veined rapa whelk, Rapana venosa, was determined using genome walking techniques in this study. The total length of the mt genome sequence of R. venosa was 15,271 bp, which is comparable to the reported Muricidae mitogenomes to date. It contained 13 protein-coding genes, 21 transfer RNA genes, and two ribosomal RNA genes. A bias towards a higher representation of nucleotides A and T (69%) was detected in the mt genome of R. venosa. A small number of non-coding nucleotides (302 bp) was detected, and the largest non-coding region was 74 bp in length.

[Long non-coding RNAs in the pathophysiology of atherosclerosis].

PubMed

Novak, Jan; Vašků, Julie Bienertová; Souček, Miroslav

2018-01-01

The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2-3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as "non-coding RNAs". Earlier the non-coding RNA was considered "the dark matter of genome", or "the junk", whose genes has accumulated in our DNA during the course of evolution. Today we already know that non-coding RNAs fulfil a variety of regulatory functions in our body - they intervene into epigenetic processes from chromatin remodelling to histone methylation, or into the transcription process itself, or even post-transcription processes. Long non-coding RNAs (lncRNA) are one of the classes of non-coding RNAs that have more than 200 nucleotides in length (non-coding RNAs with less than 200 nucleotides in length are called small non-coding RNAs). lncRNAs represent a widely varied and large group of molecules with diverse regulatory functions. We can identify them in all thinkable cell types or tissues, or even in an extracellular space, which includes blood, specifically plasma. Their levels change during the course of organogenesis, they are specific to different tissues and their changes also occur along with the development of different illnesses, including atherosclerosis. This review article aims to present lncRNAs problematics in general and then focuses on some of their specific representatives in relation to the process of atherosclerosis (i.e. we describe lncRNA involvement in the biology of endothelial cells, vascular smooth muscle cells or immune cells), and we further describe possible clinical potential of lncRNA, whether in diagnostics or therapy of atherosclerosis and its clinical manifestations.Key words: atherosclerosis - lincRNA - lncRNA - MALAT - MIAT.

Validation of Small RNAs In Xylella fastidiosa by qRT-PCR

USDA-ARS?s Scientific Manuscript database

Xylella fastidiosa causes many economically important crop diseases including almond leaf scorch disease and Pierce’ disease of grapevine. Although non-coding small RNAs (sRNAs) are regarded as ubiquitous regulatory elements in bacteria, research attention to sRNAs in X. fastidiosa has been limited...

Noxa/Mcl-1 Balance Regulates Susceptibility of Cells to Camptothecin-Induced Apoptosis1

PubMed Central

Mei, Yide; Xie, Chongwei; Xie, Wei; Tian, Xu; Li, Mei; Wu, Mian

2007-01-01

Although camptothecin (CPT) has been reported to induce apoptosis in various cancer cells, the molecular details of this regulation remain largely unknown. In this study, we demonstrate that BH3-only protein Noxa is upregulated during CPT-induced apoptosis, which is independent of p53. In addition, we show that phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is responsible for Noxa's induction. Luciferase assay and cAMP response element binding protein (CREB) knockdown experiments further demonstrate that CREB is involved in the transcriptional upregulation of Noxa. Moreover, blocking Noxa expression using specific small interfering ribonucleic acid (siRNA) significantly reduces the apoptosis in response to CPT, indicating that Noxa is an essential mediator for CPT-induced apoptosis. Interestingly, antiapoptotic Mcl-1 was also upregulated through PI3K/Akt signaling pathway upon CPT treatment. Using immunoprecipitation assay, Noxa was found to interact with Mcl-1 in the presence or absence of CPT. Knockdown of Mcl-1 expression by short hairpin ribonucleic acid (shRNA) was shown to potentiate CPT-induced apoptosis. Consistently, ectopic overexpression of Mcl-1 rescued cells from apoptosis induced by CPT. Cells coexpressing Noxa and Mcl-1 at different ratio correlates well with the extent of apoptosis, suggesting that the balance between Noxa and Mcl-1 may determine the susceptibility of HeLa cells to CPT-induced apoptosis. PMID:17971907

Fast, clash-free RNA conformational morphing using molecular junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus

Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less

Fast, clash-free RNA conformational morphing using molecular junctions

DOE PAGES

Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus; ...

2017-03-13

Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less

The effect of tRNA levels on decoding times of mRNA codons.

PubMed

Dana, Alexandra; Tuller, Tamir

2014-08-01

The possible effect of transfer ribonucleic acid (tRNA) concentrations on codons decoding time is a fundamental biomedical research question; however, due to a large number of variables affecting this process and the non-direct relation between them, a conclusive answer to this question has eluded so far researchers in the field. In this study, we perform a novel analysis of the ribosome profiling data of four organisms which enables ranking the decoding times of different codons while filtering translational phenomena such as experimental biases, extreme ribosomal pauses and ribosome traffic jams. Based on this filtering, we show for the first time that there is a significant correlation between tRNA concentrations and the codons estimated decoding time both in prokaryotes and in eukaryotes in natural conditions (-0.38 to -0.66, all P values <0.006); in addition, we show that when considering tRNA concentrations, codons decoding times are not correlated with aminoacyl-tRNA levels. The reported results support the conjecture that translation efficiency is directly influenced by the tRNA levels in the cell. Thus, they should help to understand the evolution of synonymous aspects of coding sequences via the adaptation of their codons to the tRNA pool. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Diversity of Antisense and Other Non-Coding RNAs in Archaea Revealed by Comparative Small RNA Sequencing in Four Pyrobaculum Species

PubMed Central

Bernick, David L.; Dennis, Patrick P.; Lui, Lauren M.; Lowe, Todd M.

2012-01-01

A great diversity of small, non-coding RNA (ncRNA) molecules with roles in gene regulation and RNA processing have been intensely studied in eukaryotic and bacterial model organisms, yet our knowledge of possible parallel roles for small RNAs (sRNA) in archaea is limited. We employed RNA-seq to identify novel sRNA across multiple species of the hyperthermophilic genus Pyrobaculum, known for unusual RNA gene characteristics. By comparing transcriptional data collected in parallel among four species, we were able to identify conserved RNA genes fitting into known and novel families. Among our findings, we highlight three novel cis-antisense sRNAs encoded opposite to key regulatory (ferric uptake regulator), metabolic (triose-phosphate isomerase), and core transcriptional apparatus genes (transcription factor B). We also found a large increase in the number of conserved C/D box sRNA genes over what had been previously recognized; many of these genes are encoded antisense to protein coding genes. The conserved opposition to orthologous genes across the Pyrobaculum genus suggests similarities to other cis-antisense regulatory systems. Furthermore, the genus-specific nature of these sRNAs indicates they are relatively recent, stable adaptations. PMID:22783241

Non-viral gene therapy for bone tissue engineering.

PubMed

Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

2013-01-01

The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis.

PubMed

Ferreira, Flávia Viana; Aguiar, Eric Roberto Guimarães Rocha; Olmo, Roenick Proveti; de Oliveira, Karla Pollyanna Vieira; Silva, Emanuele Guimarães; Sant'Anna, Maurício Roberto Viana; Gontijo, Nelder de Figueiredo; Kroon, Erna Geessien; Imler, Jean Luc; Marques, João Trindade

2018-06-01

Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.

A subset of conserved mammalian long non-coding RNAs are fossils of ancestral protein-coding genes.

PubMed

Hezroni, Hadas; Ben-Tov Perry, Rotem; Meir, Zohar; Housman, Gali; Lubelsky, Yoav; Ulitsky, Igor

2017-08-30

Only a small portion of human long non-coding RNAs (lncRNAs) appear to be conserved outside of mammals, but the events underlying the birth of new lncRNAs in mammals remain largely unknown. One potential source is remnants of protein-coding genes that transitioned into lncRNAs. We systematically compare lncRNA and protein-coding loci across vertebrates, and estimate that up to 5% of conserved mammalian lncRNAs are derived from lost protein-coding genes. These lncRNAs have specific characteristics, such as broader expression domains, that set them apart from other lncRNAs. Fourteen lncRNAs have sequence similarity with the loci of the contemporary homologs of the lost protein-coding genes. We propose that selection acting on enhancer sequences is mostly responsible for retention of these regions. As an example of an RNA element from a protein-coding ancestor that was retained in the lncRNA, we describe in detail a short translated ORF in the JPX lncRNA that was derived from an upstream ORF in a protein-coding gene and retains some of its functionality. We estimate that ~ 55 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs. Some lncRNAs inherited regulatory elements influencing transcription and translation from their protein-coding ancestors and those elements can influence the expression breadth and functionality of these lncRNAs.

Clearance of HCV RNA following acute hepatitis A superinfection.

PubMed

Cacopardo, B; Nunnari, G; Nigro, L

2009-05-01

A transient reduction of hepatitis C virus replication during the course of acute hepatitis A virus infection has already been reported in the literature. The present study reports the case study of a subject with chronic hepatitis due to hepatitis C virus who went on to develop an acute hepatitis A. From the early onset of acute disease, hepatitis C virus ribonucleic acid became undetectable. Following recovery from acute hepatitis, alanine amino-transferase levels became persistently normal and liver biopsy revealed a reduction in the Knodell histological activity index score. Hepatitis C virus ribonucleic acid clearance was maintained up to 4 years after the onset of acute hepatitis A. During the course of the acute disease, a sharp increase in interferon gamma levels was detected in serum and in the supernatant of both unstimulated and phytoemagglutinin/lipopolysaccharide-stimulated peripheral blood mononuclear cells. Interferon gamma levels were still high 3 months later. We hypothesize that acute hepatitis A virus superinfection during the course of chronic hepatitis C may lead to hepatitis C virus ribonucleic acid clearance through an immunological mechanism related to interferon gamma production.

An RNA tool kit to study the status of mouse ES cells: sex determination and stemness.

PubMed

Jay, F; Ciaudo, C

2013-09-01

Mouse embryonic stem cells (mESCs) are pluripotent stem cells derived from the inner cell mass of the blastocyst. They can be maintained under controlled culture conditions in a pluripotent state, or be induced to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. Several studies have characterised the coding and non-coding (nc) RNA repertoires of mESCs, uncovering highly dynamic variations during the process of differentiation, but also qualitative differences pertaining to sex. For example, up-regulation of the long non-coding RNA Xist on the X chromosome induces gene silencing and X inactivation exclusively during female mESC differentiation. In contrast, specific small RNAs have been shown to be up-regulated during male mESC differentiation. Here, we illustrate how a small set of key coding and ncRNAs can be exploited as dynamic and sensitive markers of the stemness and/or the differentiation status of male or female mESC lines. We describe adapted techniques for the extended characterization and analysis of mESCs from as little material as that cultured in a single 75cm(2) flask. Copyright © 2013 Elsevier Inc. All rights reserved.

RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines

PubMed Central

Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, Marialucia; Raggi, Chiara; Gissi, Clarissa; D’Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C.

2017-01-01

Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell lines: HuH7, Hep3B, HepG2 (hepato-cellular carcinoma) and HuH6 (hepatoblastoma), generating two different sets of sequencing libraries for each. One library was size-selected for small RNAs and the other targeted the whole transcriptome. Here are reported genome wide data of the expression level of coding and non-coding transcripts, microRNAs, isomiRs and snoRNAs providing the first comprehensive overview of the extracellular-vesicle RNA cargo released from LC cell lines. The EV-RNA expression profiles of the four liver cancer cell lines share a similar background, but cell-specific features clearly emerge showing the marked heterogeneity of the EV-cargo among the individual cell lines, evident both for the coding and non-coding RNA species. PMID:29137313

Ribonucleic Acid Synthesis and Glutamate Excretion in Escherichia coli

PubMed Central

Broda, Paul

1968-01-01

Cultures of Escherichia coli excreted glutamate into the medium when protein synthesis was blocked in RCrel strains or when it was blocked with chloramphenicol in either RCstr or RCrel strains. Both of these conditions resulted in continued ribonucleic acid (RNA) synthesis in the absence of protein synthesis. Glutamate was also excreted by both RCstr and RCrel strains when RNA synthesis was inhibited by uracil starvation or by treatment with actinomycin D. It is proposed that, in each of these cases, glutamate excretion resulted from an increase in the permeability of the cell membrane. PMID:4973126

Cloud Computing for Complex Performance Codes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, Gordon John; Hadgu, Teklu; Klein, Brandon Thorin

This report describes the use of cloud computing services for running complex public domain performance assessment problems. The work consisted of two phases: Phase 1 was to demonstrate complex codes, on several differently configured servers, could run and compute trivial small scale problems in a commercial cloud infrastructure. Phase 2 focused on proving non-trivial large scale problems could be computed in the commercial cloud environment. The cloud computing effort was successfully applied using codes of interest to the geohydrology and nuclear waste disposal modeling community.

StarScan: a web server for scanning small RNA targets from degradome sequencing data.

PubMed

Liu, Shun; Li, Jun-Hao; Wu, Jie; Zhou, Ke-Ren; Zhou, Hui; Yang, Jian-Hua; Qu, Liang-Hu

2015-07-01

Endogenous small non-coding RNAs (sRNAs), including microRNAs, PIWI-interacting RNAs and small interfering RNAs, play important gene regulatory roles in animals and plants by pairing to the protein-coding and non-coding transcripts. However, computationally assigning these various sRNAs to their regulatory target genes remains technically challenging. Recently, a high-throughput degradome sequencing method was applied to identify biologically relevant sRNA cleavage sites. In this study, an integrated web-based tool, StarScan (sRNA target Scan), was developed for scanning sRNA targets using degradome sequencing data from 20 species. Given a sRNA sequence from plants or animals, our web server performs an ultrafast and exhaustive search for potential sRNA-target interactions in annotated and unannotated genomic regions. The interactions between small RNAs and target transcripts were further evaluated using a novel tool, alignScore. A novel tool, degradomeBinomTest, was developed to quantify the abundance of degradome fragments located at the 9-11th nucleotide from the sRNA 5' end. This is the first web server for discovering potential sRNA-mediated RNA cleavage events in plants and animals, which affords mechanistic insights into the regulatory roles of sRNAs. The StarScan web server is available at http://mirlab.sysu.edu.cn/starscan/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Global assessment of small RNAs reveals a non-coding transcript involved in biofilm formation and attachment in Acinetobacter baumannii ATCC 17978

PubMed Central

Pérez, Astrid; Gómez, Manuel J.; Gayoso, Carmen; Vallejo, Juan A.; Ohneck, Emily J.; Valle, Jaione; Actis, Luis A.; Beceiro, Alejandro; Bou, Germán

2017-01-01

Many strains of Acinetobacter baumannii have been described as being able to form biofilm. Small non-coding RNAs (sRNAs) control gene expression in many regulatory circuits in bacteria. The aim of the present work was to provide a global description of the sRNAs produced both by planktonic and biofilm-associated (sessile) cells of A. baumannii ATCC 17978, and to compare the corresponding gene expression profiles to identify sRNAs molecules associated to biofilm formation and virulence. sRNA was extracted from both planktonic and sessile cells and reverse transcribed. cDNA was subjected to 454-pyrosequencing using the GS-FLX Titanium chemistry. The global analysis of the small RNA transcriptome revealed different sRNA expression patterns in planktonic and biofilm associated cells, with some of the transcripts only expressed or repressed in sessile bacteria. A total of 255 sRNAs were detected, with 185 of them differentially expressed in the different types of cells. A total of 9 sRNAs were expressed only in biofilm cells, while the expression of other 21 coding regions were repressed only in biofilm cells. Strikingly, the expression level of the sRNA 13573 was 120 times higher in biofilms than in planktonic cells, an observation that prompted us to further investigate the biological role of this non-coding transcript. Analyses of an isogenic mutant and over-expressing strains revealed that the sRNA 13573 gene is involved in biofilm formation and attachment to A549 human alveolar epithelial cells. The present work serves as a basis for future studies examining the complex regulatory network that regulate biofilm biogenesis and attachment to eukaryotic cells in A. baumannii ATCC 17978. PMID:28763494

Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.

PubMed

Costales, Matthew G; Rzuczek, Suzanne G; Disney, Matthew D

2016-06-01

Potential RNA targets for chemical probes and therapeutic modalities are pervasive in the transcriptome. Oligonucleotide-based therapeutics are commonly used to target RNA sequence. Small molecules are emerging as a modality to target RNA structures selectively, but their development is still in its infancy. In this work, we compare the activity of oligonucleotides and several classes of small molecules that target the non-coding r(CCUG) repeat expansion (r(CCUG)(exp)) that causes myotonic dystrophy type 2 (DM2), an incurable disease that is the second-most common cause of adult onset muscular dystrophy. Small molecule types investigated include monomers, dimers, and multivalent compounds synthesized on-site by using RNA-templated click chemistry. Oligonucleotides investigated include phosphorothioates that cleave their target and vivo-morpholinos that modulate target RNA activity via binding. We show that compounds assembled on-site that recognize structure have the highest potencies amongst small molecules and are similar in potency to a vivo-morpholino modified oligonucleotide that targets sequence. These studies are likely to impact the design of therapeutic modalities targeting other repeats expansions that cause fragile X syndrome and amyotrophic lateral sclerosis, for example. Copyright © 2016. Published by Elsevier Ltd.

Small non coding RNAs in adipocyte biology and obesity.

PubMed

Amri, Ez-Zoubir; Scheideler, Marcel

2017-11-15

Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs. ncRNAs regulate gene expression at the transcriptional and post-transcriptional level. Numerous studies described the involvement of ncRNAs in the pathogenesis of many diseases including obesity and associated metabolic disorders. ncRNAs represent potential diagnostic biomarkers and promising therapeutic targets. In this review, we focused on small ncRNAs involved in the formation and function of adipocytes and obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

A Scalable Architecture of a Structured LDPC Decoder

NASA Technical Reports Server (NTRS)

Lee, Jason Kwok-San; Lee, Benjamin; Thorpe, Jeremy; Andrews, Kenneth; Dolinar, Sam; Hamkins, Jon

2004-01-01

We present a scalable decoding architecture for a certain class of structured LDPC codes. The codes are designed using a small (n,r) protograph that is replicated Z times to produce a decoding graph for a (Z x n, Z x r) code. Using this architecture, we have implemented a decoder for a (4096,2048) LDPC code on a Xilinx Virtex-II 2000 FPGA, and achieved decoding speeds of 31 Mbps with 10 fixed iterations. The implemented message-passing algorithm uses an optimized 3-bit non-uniform quantizer that operates with 0.2dB implementation loss relative to a floating point decoder.

FDA’s Nozzle Numerical Simulation Challenge: Non-Newtonian Fluid Effects and Blood Damage

PubMed Central

Trias, Miquel; Arbona, Antonio; Massó, Joan; Miñano, Borja; Bona, Carles

2014-01-01

Data from FDA’s nozzle challenge–a study to assess the suitability of simulating fluid flow in an idealized medical device–is used to validate the simulations obtained from a numerical, finite-differences code. Various physiological indicators are computed and compared with experimental data from three different laboratories, getting a very good agreement. Special care is taken with the derivation of blood damage (hemolysis). The paper is focused on the laminar regime, in order to investigate non-Newtonian effects (non-constant fluid viscosity). The code can deal with these effects with just a small extra computational cost, improving Newtonian estimations up to a ten percent. The relevance of non-Newtonian effects for hemolysis parameters is discussed. PMID:24667931

Identification of mRNA-like non-coding RNAs and validation of a mighty one named MAR in Panax ginseng.

PubMed

Wang, Meizhen; Wu, Bin; Chen, Chao; Lu, Shanfa

2015-03-01

Increasing evidence suggests that long non-coding RNAs (lncRNAs) play significant roles in plants. However, little is known about lncRNAs in Panax ginseng C. A. Meyer, an economically significant medicinal plant species. A total of 3,688 mRNA-like non-coding RNAs (mlncRNAs), a class of lncRNAs, were identified in P. ginseng. Approximately 40% of the identified mlncRNAs were processed into small RNAs, implying their regulatory roles via small RNA-mediated mechanisms. Eleven miRNA-generating mlncRNAs also produced siRNAs, suggesting the coordinated production of miRNAs and siRNAs in P. ginseng. The mlncRNA-derived small RNAs might be 21-, 22-, or 24-nt phased and could be generated from both or only one strand of mlncRNAs, or from super long hairpin structures. A full-length mlncRNA, termed MAR (multiple-function-associated mlncRNA), was cloned. It generated the most abundant siRNAs. The MAR siRNAs were predominantly 24-nt and some of them were distributed in a phased pattern. A total of 228 targets were predicted for 71 MAR siRNAs. Degradome sequencing validated 68 predicted targets involved in diverse metabolic pathways, suggesting the significance of MAR in P. ginseng. Consistently, MAR was detected in all tissues analyzed and responded to methyl jasmonate (MeJA) treatment. It sheds light on the function of mlncRNAs in plants. © 2014 Institute of Botany, Chinese Academy of Sciences.

Role of long non-coding RNA in drug resistance in non-small cell lung cancer.

PubMed

Wang, Leirong; Ma, Leina; Xu, Fei; Zhai, Wenxin; Dong, Shenghua; Yin, Ling; Liu, Jia; Yu, Zhuang

2018-05-03

Lung cancer is the leading cause of cancer-associated death, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Many drugs have been used to treat NSCLC in order to improve patient prognosis. Platinum-based chemotherapy is the first-line treatment for locally advanced or metastatic patients. For patients with activating EGFR mutations, tyrosine kinase inhibitors are the best treatment choice. NSCLC initially exhibits an excellent response to treatment; however, acquired resistance has been observed in many patients, leading to ineffective treatment. Clinical resistance is an impediment in the treatment of patients with advanced NSCLC. Many sequencing technologies have shown that long non-coding RNA (lncRNA) is expressed differently between drug-resistant and drug-sensitive lung cancer cells. We review the literature on lncRNA in drug resistance of NSCLC. The aim of this review is to gain insight into the molecular mechanisms of drug resistance, mainly focusing on the role of lncRNA in NSCLC. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Transcription and DNA Damage: Holding Hands or Crossing Swords?

PubMed

D'Alessandro, Giuseppina; d'Adda di Fagagna, Fabrizio

2017-10-27

Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Next-Generation Sequencing of Protein-Coding and Long Non-protein-Coding RNAs in Two Types of Exosomes Derived from Human Whole Saliva.

PubMed

Ogawa, Yuko; Tsujimoto, Masafumi; Yanoshita, Ryohei

2016-01-01

Exosomes are small extracellular vesicles containing microRNAs and mRNAs that are produced by various types of cells. We previously used ultrafiltration and size-exclusion chromatography to isolate two types of human salivary exosomes (exosomes I, II) that are different in size and proteomes. We showed that salivary exosomes contain large repertoires of small RNAs. However, precise information regarding long RNAs in salivary exosomes has not been fully determined. In this study, we investigated the compositions of protein-coding RNAs (pcRNAs) and long non-protein-coding RNAs (lncRNAs) of exosome I, exosome II and whole saliva (WS) by next-generation sequencing technology. Although 11% of all RNAs were commonly detected among the three samples, the compositions of reads mapping to known RNAs were similar. The most abundant pcRNA is ribosomal RNA protein, and pcRNAs of some salivary proteins such as S100 calcium-binding protein A8 (protein S100-A8) were present in salivary exosomes. Interestingly, lncRNAs of pseudogenes (presumably, processed pseudogenes) were abundant in exosome I, exosome II and WS. Translationally controlled tumor protein gene, which plays an important role in cell proliferation, cell death and immune responses, was highly expressed as pcRNA and pseudogenes in salivary exosomes. Our results show that salivary exosomes contain various types of RNAs such as pseudogenes and small RNAs, and may mediate intercellular communication by transferring these RNAs to target cells as gene expression regulators.

CrcZ and CrcX regulate carbon utilization in Pseudomonas syringae pathovar tomato strain DC3000

USDA-ARS?s Scientific Manuscript database

Small non-coding RNAs (ncRNAs) are important components of many regulatory pathways in bacteria and play key roles in regulating factors important for virulence. Carbon catabolite repression control is modulated by small RNAs (crcZ or crcZ and crcY) in Pseudomonas aeruginosa and Pseudomonas putida. ...

75 FR 15492 - Paperwork Reduction Act of 1995, as Amended by Public Law 104-13; Proposed Collection, Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

.... James W. Sample, Director of CyberSecurity. [FR Doc. 2010-6904 Filed 3-26-10; 8:45 am] BILLING CODE 8120...: Individuals or households, state or local governments, farms, businesses, or other for-profit Federal agencies or employees, non-profit institutions, small businesses or organizations. Small Businesses or...

Divergent patterns of endogenous small RNA populations from seed and vegetative tissues of Glycine max

USDA-ARS?s Scientific Manuscript database

Background: Small non-coding RNAs (smRNAs) are known to have major roles in gene regulation in eukaryotes. In plants, knowledge of the biogenesis and mechanisms of action of smRNA classes including microRNAs (miRNAs), short interfering RNAs (siRNAs), and trans-acting siRNAs (tasiRNAs) has been gaine...

Study of Two-Dimensional Compressible Non-Acoustic Modeling of Stirling Machine Type Components

NASA Technical Reports Server (NTRS)

Tew, Roy C., Jr.; Ibrahim, Mounir B.

2001-01-01

A two-dimensional (2-D) computer code was developed for modeling enclosed volumes of gas with oscillating boundaries, such as Stirling machine components. An existing 2-D incompressible flow computer code, CAST, was used as the starting point for the project. CAST was modified to use the compressible non-acoustic Navier-Stokes equations to model an enclosed volume including an oscillating piston. The devices modeled have low Mach numbers and are sufficiently small that the time required for acoustics to propagate across them is negligible. Therefore, acoustics were excluded to enable more time efficient computation. Background information about the project is presented. The compressible non-acoustic flow assumptions are discussed. The governing equations used in the model are presented in transport equation format. A brief description is given of the numerical methods used. Comparisons of code predictions with experimental data are then discussed.

The expanding regulatory universe of p53 in gastrointestinal cancer.

PubMed

Fesler, Andrew; Zhang, Ning; Ju, Jingfang

2016-01-01

Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas.

PubMed

Lin, Fan; Shi, Jianhui; Wang, Hanlin L; Ma, Xiao-Jun; Monroe, Robert; Luo, Yuling; Chen, Zongming; Liu, Haiyan

2018-05-09

Inconsistent data on detection of albumin expression by ribonucleic acid (RNA) in situ hybridization have been reported. We investigated the utility of RNAscope (Advanced Cell Diagnostics, Hayward, CA) in detection of albumin in hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (ICCs), and carcinomas from various organs using manual and automated staining. RNAscope for albumin detection was performed on 482 cases on tissue microarray sections and on 22 cases of ICC, including 14 surgical resection and eight core biopsy specimens. Thirty-six of 37 (97%) HCCs had detectable mRNA, whereas all non-HCC and non-ICC cases, except one lung adenocarcinoma, were negative for albumin. Fourteen of 22 ICCs (64%) were positive for albumin. RNAscope for albumin is highly sensitive and specific for identifying HCCs and is highly specific and moderately sensitive for detection of ICCs; however, rare carcinomas (non-HCC, non-ICC, and those with no hepatoid histomorphology) can also have aberrant expression of albumin.

Error rates and resource overheads of encoded three-qubit gates

NASA Astrophysics Data System (ADS)

Takagi, Ryuji; Yoder, Theodore J.; Chuang, Isaac L.

2017-10-01

A non-Clifford gate is required for universal quantum computation, and, typically, this is the most error-prone and resource-intensive logical operation on an error-correcting code. Small, single-qubit rotations are popular choices for this non-Clifford gate, but certain three-qubit gates, such as Toffoli or controlled-controlled-Z (ccz), are equivalent options that are also more suited for implementing some quantum algorithms, for instance, those with coherent classical subroutines. Here, we calculate error rates and resource overheads for implementing logical ccz with pieceable fault tolerance, a nontransversal method for implementing logical gates. We provide a comparison with a nonlocal magic-state scheme on a concatenated code and a local magic-state scheme on the surface code. We find the pieceable fault-tolerance scheme particularly advantaged over magic states on concatenated codes and in certain regimes over magic states on the surface code. Our results suggest that pieceable fault tolerance is a promising candidate for fault tolerance in a near-future quantum computer.

The origins and evolutionary history of human non-coding RNA regulatory networks.

PubMed

Sherafatian, Masih; Mowla, Seyed Javad

2017-04-01

The evolutionary history and origin of the regulatory function of animal non-coding RNAs are not well understood. Lack of conservation of long non-coding RNAs and small sizes of microRNAs has been major obstacles in their phylogenetic analysis. In this study, we tried to shed more light on the evolution of ncRNA regulatory networks by changing our phylogenetic strategy to focus on the evolutionary pattern of their protein coding targets. We used available target databases of miRNAs and lncRNAs to find their protein coding targets in human. We were able to recognize evolutionary hallmarks of ncRNA targets by phylostratigraphic analysis. We found the conventional 3'-UTR and lesser known 5'-UTR targets of miRNAs to be enriched at three consecutive phylostrata. Firstly, in eukaryata phylostratum corresponding to the emergence of miRNAs, our study revealed that miRNA targets function primarily in cell cycle processes. Moreover, the same overrepresentation of the targets observed in the next two consecutive phylostrata, opisthokonta and eumetazoa, corresponded to the expansion periods of miRNAs in animals evolution. Coding sequence targets of miRNAs showed a delayed rise at opisthokonta phylostratum, compared to the 3' and 5' UTR targets of miRNAs. LncRNA regulatory network was the latest to evolve at eumetazoa.

Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells.

PubMed

Autour, Alexis; C Y Jeng, Sunny; D Cawte, Adam; Abdolahzadeh, Amir; Galli, Angela; Panchapakesan, Shanker S S; Rueda, David; Ryckelynck, Michael; Unrau, Peter J

2018-02-13

Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.

An expanding universe of the non-coding genome in cancer biology.

PubMed

Xue, Bin; He, Lin

2014-06-01

Neoplastic transformation is caused by accumulation of genetic and epigenetic alterations that ultimately convert normal cells into tumor cells with uncontrolled proliferation and survival, unlimited replicative potential and invasive growth [Hanahan,D. et al. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646-674]. Although the majority of the cancer studies have focused on the functions of protein-coding genes, emerging evidence has started to reveal the importance of the vast non-coding genome, which constitutes more than 98% of the human genome. A number of non-coding RNAs (ncRNAs) derived from the 'dark matter' of the human genome exhibit cancer-specific differential expression and/or genomic alterations, and it is increasingly clear that ncRNAs, including small ncRNAs and long ncRNAs (lncRNAs), play an important role in cancer development by regulating protein-coding gene expression through diverse mechanisms. In addition to ncRNAs, nearly half of the mammalian genomes consist of transposable elements, particularly retrotransposons. Once depicted as selfish genomic parasites that propagate at the expense of host fitness, retrotransposon elements could also confer regulatory complexity to the host genomes during development and disease. Reactivation of retrotransposons in cancer, while capable of causing insertional mutagenesis and genome rearrangements to promote oncogenesis, could also alter host gene expression networks to favor tumor development. Taken together, the functional significance of non-coding genome in tumorigenesis has been previously underestimated, and diverse transcripts derived from the non-coding genome could act as integral functional components of the oncogene and tumor suppressor network. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Investigative and extrapolative role of microRNAs' genetic expression in breast carcinoma.

PubMed

Usmani, Ambreen; Shoro, Amir Ali; Shirazi, Bushra; Memon, Zahida

2016-01-01

MicroRNAs (miRs) are non-coding ribonucleic acids consisting of about 18-22 nucleotide bases. Expression of several miRs can be altered in breast carcinomas in comparison to healthy breast tissue, or between various subtypes of breast cancer. These are regulated as either oncogene or tumor suppressors, this shows that their expression is misrepresented in cancers. Some miRs are specifically associated with breast cancer and are affected by cancer-restricted signaling pathways e.g. downstream of estrogen receptor-α or HER2/neu. Connection of multiple miRs with breast cancer, and the fact that most of these post transcript structures may transform complex functional networks of mRNAs, identify them as potential investigative, extrapolative and predictive tumor markers, as well as possible targets for treatment. Investigative tools that are currently available are RNA-based molecular techniques. An additional advantage related to miRs in oncology is that they are remarkably stable and are notably detectable in serum and plasma. Literature search was performed by using database of PubMed, the keywords used were microRNA (52 searches) AND breast cancer (169 searches). PERN was used by database of Bahria University, this included literature and articles from international sources; 2 articles from Pakistan on this topic were consulted (one in international journal and one in a local journal). Of these, 49 articles were shortlisted which discussed relation of microRNA genetic expression in breast cancer. These articles were consulted for this review.

An R132H Mutation in Isocitrate Dehydrogenase 1 Enhances p21 Expression and Inhibits Phosphorylation of Retinoblastoma Protein in Glioma Cells

PubMed Central

Miyata, Satsuki; Urabe, Masashi; Gomi, Akira; Nagai, Mutsumi; Yamaguchi, Takashi; Tsukahara, Tomonori; Mizukami, Hiroaki; Kume, Akihiro; Ozawa, Keiya; Watanabe, Eiju

2013-01-01

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1R132H-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1R132H-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progressionof the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation. PMID:24077277

An R132H mutation in isocitrate dehydrogenase 1 enhances p21 expression and inhibits phosphorylation of retinoblastoma protein in glioma cells.

PubMed

Miyata, Satsuki; Urabe, Masashi; Gomi, Akira; Nagai, Mutsumi; Yamaguchi, Takashi; Tsukahara, Tomonori; Mizukami, Hiroaki; Kume, Akihiro; Ozawa, Keiya; Watanabe, Eiju

2013-01-01

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1(R132H)-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1(R132H)-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progression of the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation.

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

NASA Astrophysics Data System (ADS)

Skupin, Michalina; Sobczak, Krzysztof; Zieliński, Ryszard; Kozak, Maciej

2016-05-01

Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small angle scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skupin, Michalina; Sobczak, Krzysztof; Zieliński, Ryszard

Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small anglemore » scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.« less

Silence of the transcripts: RNA interference in medicine.

PubMed

Barik, Sailen

2005-10-01

Silencing of gene expression by ribonucleic acid (RNA), known as RNA interference (RNAi), is now recognized as a major means of gene regulation in biology. In this mechanism, small noncoding double-stranded RNA molecules knock down gene expression through a variety of mechanisms that include messenger RNA (mRNA) degradation, inhibition of mRNA translation, or chromatin remodeling. The posttranscriptional mechanism of RNAi has been embraced by researchers as a powerful tool for generating deficient phenotypes without mutating the gene. In parallel, exciting recent results have promised its application in disease therapy. This review aims to summarize the current knowledge in this area and provide a roadmap that may eventually launch RNAi from the research bench to the medicine chest.

GRIL-seq provides a method for identifying direct targets of bacterial small regulatory RNA by in vivo proximity ligation.

PubMed

Han, Kook; Tjaden, Brian; Lory, Stephen

2016-12-22

The first step in the post-transcriptional regulatory function of most bacterial small non-coding RNAs (sRNAs) is base pairing with partially complementary sequences of targeted transcripts. We present a simple method for identifying sRNA targets in vivo and defining processing sites of the regulated transcripts. The technique, referred to as global small non-coding RNA target identification by ligation and sequencing (GRIL-seq), is based on preferential ligation of sRNAs to the ends of base-paired targets in bacteria co-expressing T4 RNA ligase, followed by sequencing to identify the chimaeras. In addition to the RNA chaperone Hfq, the GRIL-seq method depends on the activity of the pyrophosphorylase RppH. Using PrrF1, an iron-regulated sRNA in Pseudomonas aeruginosa, we demonstrated that direct regulatory targets of this sRNA can readily be identified. Therefore, GRIL-seq represents a powerful tool not only for identifying direct targets of sRNAs in a variety of environments, but also for uncovering novel roles for sRNAs and their targets in complex regulatory networks.

Phosphodiester models for cleavage of nucleic acids

PubMed Central

2018-01-01

Nucleic acids that store and transfer biological information are polymeric diesters of phosphoric acid. Cleavage of the phosphodiester linkages by protein enzymes, nucleases, is one of the underlying biological processes. The remarkable catalytic efficiency of nucleases, together with the ability of ribonucleic acids to serve sometimes as nucleases, has made the cleavage of phosphodiesters a subject of intensive mechanistic studies. In addition to studies of nucleases by pH-rate dependency, X-ray crystallography, amino acid/nucleotide substitution and computational approaches, experimental and theoretical studies with small molecular model compounds still play a role. With small molecules, the importance of various elementary processes, such as proton transfer and metal ion binding, for stabilization of transition states may be elucidated and systematic variation of the basicity of the entering or departing nucleophile enables determination of the position of the transition state on the reaction coordinate. Such data is important on analyzing enzyme mechanisms based on synergistic participation of several catalytic entities. Many nucleases are metalloenzymes and small molecular models offer an excellent tool to construct models for their catalytic centers. The present review tends to be an up to date summary of what has been achieved by mechanistic studies with small molecular phosphodiesters. PMID:29719577

Evaluation of Shape and Textural Features from CT as Prognostic Biomarkers in Non-small Cell Lung Cancer.

PubMed

Bianconi, Francesco; Fravolini, Mario Luca; Bello-Cerezo, Raquel; Minestrini, Matteo; Scialpi, Michele; Palumbo, Barbara

2018-04-01

We retrospectively investigated the prognostic potential (correlation with overall survival) of 9 shape and 21 textural features from non-contrast-enhanced computed tomography (CT) in patients with non-small-cell lung cancer. We considered a public dataset of 203 individuals with inoperable, histologically- or cytologically-confirmed NSCLC. Three-dimensional shape and textural features from CT were computed using proprietary code and their prognostic potential evaluated through four different statistical protocols. Volume and grey-level run length matrix (GLRLM) run length non-uniformity were the only two features to pass all four protocols. Both features correlated negatively with overall survival. The results also showed a strong dependence on the evaluation protocol used. Tumour volume and GLRLM run-length non-uniformity from CT were the best predictor of survival in patients with non-small-cell lung cancer. We did not find enough evidence to claim a relationship with survival for the other features. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - I. Nucleotide composition of RNAs from the liver and tumor tissues of rats.

PubMed

Ratkiewicz, A; Galasinski, W

1976-01-01

The characteristics of the ribonucleic acids of Guerin tumor was the subject of this work. The effect of tumor development on the structure of the ribonucleic acids in the liver of tumor bearing rats was studied. Some differences of nucleotide compositions in RNAs isolated from subcellular fractions of liver of control and tumor bearing rats and of cancer tissue were observed. The nucleotide compositions of cancer nuclear RNA is distinctly different from liver RNA. The changes in primary structure of liver RNAs due by development of tumor in rats may be result of metabolic peculiarities of these RNAs.

Non-coding RNAs in crop genetic modification: considerations and predictable environmental risk assessments (ERA).

PubMed

Ramesh, S V

2013-09-01

Of late non-coding RNAs (ncRNAs)-mediated gene silencing is an influential tool deliberately deployed to negatively regulate the expression of targeted genes. In addition to the widely employed small interfering RNA (siRNA)-mediated gene silencing approach, other variants like artificial miRNA (amiRNA), miRNA mimics, and artificial transacting siRNAs (tasiRNAs) are being explored and successfully deployed in developing non-coding RNA-based genetically modified plants. The ncRNA-based gene manipulations are typified with mobile nature of silencing signals, interference from viral genome-derived suppressor proteins, and an obligation for meticulous computational analysis to prevaricate any inadvertent effects. In a broad sense, risk assessment inquiries for genetically modified plants based on the expression of ncRNAs are competently addressed by the environmental risk assessment (ERA) models, currently in vogue, designed for the first generation transgenic plants which are based on the expression of heterologous proteins. Nevertheless, transgenic plants functioning on the foundation of ncRNAs warrant due attention with respect to their unique attributes like off-target or non-target gene silencing effects, small RNAs (sRNAs) persistence, food and feed safety assessments, problems in detection and tracking of sRNAs in food, impact of ncRNAs in plant protection measures, effect of mutations etc. The role of recent developments in sequencing techniques like next generation sequencing (NGS) and the ERA paradigm of the different countries in vogue are also discussed in the context of ncRNA-based gene manipulations.

Measurement-free implementations of small-scale surface codes for quantum-dot qubits

NASA Astrophysics Data System (ADS)

Ercan, H. Ekmel; Ghosh, Joydip; Crow, Daniel; Premakumar, Vickram N.; Joynt, Robert; Friesen, Mark; Coppersmith, S. N.

2018-01-01

The performance of quantum-error-correction schemes depends sensitively on the physical realizations of the qubits and the implementations of various operations. For example, in quantum-dot spin qubits, readout is typically much slower than gate operations, and conventional surface-code implementations that rely heavily on syndrome measurements could therefore be challenging. However, fast and accurate reset of quantum-dot qubits, without readout, can be achieved via tunneling to a reservoir. Here we propose small-scale surface-code implementations for which syndrome measurements are replaced by a combination of Toffoli gates and qubit reset. For quantum-dot qubits, this enables much faster error correction than measurement-based schemes, but requires additional ancilla qubits and non-nearest-neighbor interactions. We have performed numerical simulations of two different coding schemes, obtaining error thresholds on the orders of 10-2 for a one-dimensional architecture that only corrects bit-flip errors and 10-4 for a two-dimensional architecture that corrects bit- and phase-flip errors.

Protograph LDPC Codes with Node Degrees at Least 3

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Jones, Christopher

2006-01-01

In this paper we present protograph codes with a small number of degree-3 nodes and one high degree node. The iterative decoding threshold for proposed rate 1/2 codes are lower, by about 0.2 dB, than the best known irregular LDPC codes with degree at least 3. The main motivation is to gain linear minimum distance to achieve low error floor. Also to construct rate-compatible protograph-based LDPC codes for fixed block length that simultaneously achieves low iterative decoding threshold and linear minimum distance. We start with a rate 1/2 protograph LDPC code with degree-3 nodes and one high degree node. Higher rate codes are obtained by connecting check nodes with degree-2 non-transmitted nodes. This is equivalent to constraint combining in the protograph. The condition where all constraints are combined corresponds to the highest rate code. This constraint must be connected to nodes of degree at least three for the graph to have linear minimum distance. Thus having node degree at least 3 for rate 1/2 guarantees linear minimum distance property to be preserved for higher rates. Through examples we show that the iterative decoding threshold as low as 0.544 dB can be achieved for small protographs with node degrees at least three. A family of low- to high-rate codes with minimum distance linearly increasing in block size and with capacity-approaching performance thresholds is presented. FPGA simulation results for a few example codes show that the proposed codes perform as predicted.

The Application of Clinical Lithotripter Shock Waves to RNA Nucleotide Delivery to Cells.

PubMed

Nwokeoha, Sandra; Carlisle, Robert; Cleveland, Robin O

2016-10-01

The delivery of genes into cells through the transfer of ribonucleic acids (RNAs) has been found to cause a change in the level of target protein expression. RNA-based transfection is conceptually more efficient than commonly delivered plasmid DNA because it does not require division or damage of the nuclear envelope, thereby increasing the chances of the cell remaining viable. Shock waves (SWs) have been found to induce cellular uptake by transiently altering the permeability of the plasma membrane, thereby overcoming a critical step in gene therapy. However, accompanying SW bio-effects include dose-dependent irreversible cell injury and cytotoxicity. Here, the effect of SWs generated by a clinical lithotripter on the viability and permeabilisation of three different cell lines in vitro was investigated. Comparison of RNA stability before and after SW exposure revealed no statistically significant difference. Optimal SW exposure parameters were identified to minimise cell death and maximise permeabilisation, and applied to enhanced green fluorescent protein (eGFP) messenger RNA (mRNA) or anti-eGFP small interfering RNA delivery. As a result, eGFP mRNA expression levels increased up to 52-fold in CT26 cells, whereas a 2-fold decrease in GFP expression was achieved after anti-eGFP small interfering RNA delivery to MCF-7/GFP cells. These results indicate that SW parameters can be employed to achieve effective nucleotide delivery, laying the foundation for non-invasive and high-tolerability RNA-based gene therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

microRNA Therapeutics in Cancer - An Emerging Concept.

PubMed

Shah, Maitri Y; Ferrajoli, Alessandra; Sood, Anil K; Lopez-Berestein, Gabriel; Calin, George A

2016-10-01

MicroRNAs (miRNAs) are an evolutionarily conserved class of small, regulatory non-coding RNAs that negatively regulate protein coding gene and other non-coding transcripts expression. miRNAs have been established as master regulators of cellular processes, and they play a vital role in tumor initiation, progression and metastasis. Further, widespread deregulation of microRNAs have been reported in several cancers, with several microRNAs playing oncogenic and tumor suppressive roles. Based on these, miRNAs have emerged as promising therapeutic tools for cancer management. In this review, we have focused on the roles of miRNAs in tumorigenesis, the miRNA-based therapeutic strategies currently being evaluated for use in cancer, and the advantages and current challenges to their use in the clinic. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin

PubMed Central

Böhmdorfer, Gudrun; Sethuraman, Shriya; Rowley, M Jordan; Krzyszton, Michal; Rothi, M Hafiz; Bouzit, Lilia; Wierzbicki, Andrzej T

2016-01-01

RNA-mediated transcriptional gene silencing is a conserved process where small RNAs target transposons and other sequences for repression by establishing chromatin modifications. A central element of this process are long non-coding RNAs (lncRNA), which in Arabidopsis thaliana are produced by a specialized RNA polymerase known as Pol V. Here we show that non-coding transcription by Pol V is controlled by preexisting chromatin modifications located within the transcribed regions. Most Pol V transcripts are associated with AGO4 but are not sliced by AGO4. Pol V-dependent DNA methylation is established on both strands of DNA and is tightly restricted to Pol V-transcribed regions. This indicates that chromatin modifications are established in close proximity to Pol V. Finally, Pol V transcription is preferentially enriched on edges of silenced transposable elements, where Pol V transcribes into TEs. We propose that Pol V may play an important role in the determination of heterochromatin boundaries. DOI: http://dx.doi.org/10.7554/eLife.19092.001 PMID:27779094

A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell

PubMed Central

Herbert, Kristina M.; Nag, Anita

2016-01-01

Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage. PMID:27271653

Non-coding glucometers among pediatric patients with diabetes: looking for the target population and an accuracy evaluation of no-coding personal glucometer.

PubMed

Fendler, Wojciech; Hogendorf, Anna; Szadkowska, Agnieszka; Młynarski, Wojciech

2011-01-01

Self-monitoring of blood glucose (SMBG) is one of the cornerstones of diabetes management. To evaluate the potential for miscoding of a personal glucometer, to define a target population among pediatric patients with diabetes for a non-coding glucometer and the accuracy of the Contour TS non-coding system. Potential for miscoding during self-monitoring of blood glucose was evaluated by means of an anonymous questionnaire, with worst and best case scenarios evaluated depending on the responses pattern. Testing of the Contour TS system was performed according to guidelines set by the national committee for clinical laboratory standards. Estimated frequency of individuals prone to non-coding ranged from 68.21% (95% 60.70- 75.72%) to 7.95% (95%CI 3.86-12.31%) for the worse and best case scenarios respectively. Factors associated with increased likelihood of non-coding were: a smaller number of tests per day, a greater number of individuals involved in testing and self-testing by the patient with diabetes. The Contour TS device showed intra- and inter-assay accuracy -95%, linear association with laboratory measurements (R2=0.99, p <0.0001) and consistent, but small bias of -1.12% (95% Confidence Interval -3.27 to 1.02%). Clarke error grid analysis showed 4% of values within the benign error zone (B) with the other measurements yielding an acceptably accurate result (zone A). The Contour TS system showed sufficient accuracy to be safely used in monitoring of pediatric diabetic patients. Patients from families with a high throughput of test-strips or multiple individuals involved in SMBG using the same meter are candidates for clinical use of such devices due to an increased risk of calibration errors.

Context of Carbonate Rocks in Heavily Eroded Martian Terrain

NASA Image and Video Library

2008-12-18

The color coding on this CRISM composite image of an area on Mars is based on infrared spectral information interpreted as evidence of various minerals present. Carbonate, which is indicative of a wet and non-acidic history, occurs in very small patches.

THE CONTENT AND RELATIVE BASE RATIOS OF RIBONUCLEIC ACID IN AMOEBA

PubMed Central

Iverson, Ray M.

1964-01-01

The amount and relative base ratios of ribonucleic acid (RNA) in the nucleus and cytoplasm of Amoeba proteus and A. dubia, and of homospecies cells obtained by nuclear transfer with A. proteus, have been determined by microelectrophoresis. In A. proteus the average amounts of RNA in the nucleus and the cytoplasm were 134. micromicrograms and 2520. micromicrograms; in A. dubia the averages for the nucleus and cytoplasm were 67. micromicrograms and 1427. micromicrograms. The relative base ratio of RNA of the nucleus is similar to that of the RNA of the cytoplasm within a species, but the two species differed in this respect. Homospecies nuclear transfer did not affect the relative base ratio or amount of RNA. PMID:14105213

Characterization of circulating transfer RNA-derived RNA fragments in cattle

PubMed Central

Casas, Eduardo; Cai, Guohong; Neill, John D.

2015-01-01

The objective was to characterize naturally occurring circulating transfer RNA-derived RNA fragments (tRFs) in cattle1. Serum from eight clinically normal adult dairy cows was collected, and small non-coding RNAs were extracted immediately after collection and sequenced by Illumina MiSeq. Sequences aligned to transfer RNA (tRNA) genes or their flanking sequences were characterized. Sequences aligned to the beginning of 5′ end of the mature tRNA were classified as tRF5; those aligned to the 3′ end of mature tRNA were classified as tRF3; and those aligned to the beginning of the 3′ end flanking sequences were classified as tRF1. There were 3,190,962 sequences that mapped to transfer RNA and small non-coding RNAs in the bovine genome. Of these, 2,323,520 were identified as tRF5s, 562 were tRF3s, and 81 were tRF1s. There were 866,799 sequences identified as other small non-coding RNAs (microRNA, rRNA, snoRNA, etc.) and were excluded from the study. The tRF5s ranged from 28 to 40 nucleotides; and 98.7% ranged from 30 to 34 nucleotides in length. The tRFs with the greatest number of sequences were derived from tRNA of histidine, glutamic acid, lysine, glycine, and valine. There was no association between number of codons for each amino acid and number of tRFs in the samples. The reason for tRF5s being the most abundant can only be explained if these sequences are associated with function within the animal. PMID:26379699

ISSOL Meeting, 7th, Barcelona, Spain, July 4-9, 1993. [Abstracts only

NASA Technical Reports Server (NTRS)

Ferris, James P. (Editor)

1994-01-01

The journal issue consists of abstracts presented at the International Society for the Study of the Origins of Life (ISSOL) conference. Topics include research on biological and chemical evolution including prebiotic evolution: cosmic and terrestrial; mechanisms of abiogenesis including synthesis and reactions of biomonomers; and analysis of cometary matter and its possible relationship to organic compounds on Earth. Theories and research on origins of ribonucleic acids (RNA), deoxyribonucleic acid (DNA), and other amino acids and complex proteins including their autocatalysis, replication, and translation are presented. Abiotic synthesis of biopolymers, mechanisms of the Genetic Code, precellular membrane systems and energetics are considered. Earth planetary evolution including early microfossils and geochemical conditions and simulations to study these conditions are discussed. The role of chirality in precellular evolution and the taxonomy and phylogeny of very simple organisms are reported. Past and future explorations in exobiology and space research directed toward study of the origins of life and solar system evolution are described.

Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells.

PubMed

Sun, Pengming; Xue, Lifang; Song, Yiyi; Mao, Xiaodan; Chen, Lili; Dong, Binhua; Braicu, Elena Loana; Sehouli, Jalid

2018-02-27

The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA ( P < 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased ( P < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased ( P < 0.001) due to the down-regulation of matriptase and HAI-1 upon increasing cisplatin concentration. However, a slight increase in matriptase and HAI-1 expression was observed in cells treated with low cisplatin concentration ( P = 0.01). Moreover, matriptase expression was associated with metastasis and invasiveness. Down-regulation of matriptase by specific Ma-SiRNA or non-specific cisplatin in matriptase/HAI-1-positive endometrial cancer cells showed promising therapeutic features.

Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells

PubMed Central

Sun, Pengming; Xue, Lifang; Song, Yiyi; Mao, Xiaodan; Chen, Lili; Dong, Binhua; Braicu, Elena Loana; Sehouli, Jalid

2018-01-01

The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA (P < 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased (P < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased (P < 0.001) due to the down-regulation of matriptase and HAI-1 upon increasing cisplatin concentration. However, a slight increase in matriptase and HAI-1 expression was observed in cells treated with low cisplatin concentration (P = 0.01). Moreover, matriptase expression was associated with metastasis and invasiveness. Down-regulation of matriptase by specific Ma-SiRNA or non-specific cisplatin in matriptase/HAI-1–positive endometrial cancer cells showed promising therapeutic features. PMID:29560101

Expression of metastasis-associated lung adenocarcinoma transcript 1 long non-coding RNA in vitro and in patients with non-small cell lung cancer.

PubMed

Lin, Ling; Li, Haiyan; Zhu, Yefei; He, Susu; Ge, Hongfei

2018-06-01

The present study aimed to investigate the association between the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNA (lncRNA) and the recurrence of non-small cell lung cancer (NSCLC) and to elucidate the potential mechanisms of MALAT1 in vitro . Between 1 June 1, 2010 and December 30, 2016, NSCLC tumor tissues and adjacent non-cancerous tissues were obtained from 120 patients with NSCLC, who had undergone surgical resection at Taizhou Hospital of Wenzhou Medical University (Linhai, China). The total RNA of tissues and cells were extracted and the expression of MALAT1 was determined using a wound healing assay and reverse transcription quantitative polymerase chain reaction. In addition, MALAT1 expression in A549 cells was silenced using small interfering RNA. The proliferation, migration and invasion of cells were then assessed using a CellTiter 96 kit and Transwell assays. MALAT1 expression was significantly increased in NSCLC samples compared with expression in adjacent non-cancerous tissues. Furthermore, the expression of MALAT1 in patients with NSCLC that exhibited recurrence was markedly higher than in those that did not. The results of the present study also demonstrated significant associations between high expression of MALAT1 and female sex, Tumor-Node-Metastasis advanced stage, vessel invasion, pathological differentiation and recurrence of patients with NSCLC. The proliferative, migratory and invasive abilities of MALAT1-silenced A549 cells were significantly decreased compared with those of control cells. MALAT1 expression was significantly increased in NSCLC tissues and was revealed to serve a role in the progression of NSCLC.

nRC: non-coding RNA Classifier based on structural features.

PubMed

Fiannaca, Antonino; La Rosa, Massimo; La Paglia, Laura; Rizzo, Riccardo; Urso, Alfonso

2017-01-01

Non-coding RNA (ncRNA) are small non-coding sequences involved in gene expression regulation of many biological processes and diseases. The recent discovery of a large set of different ncRNAs with biologically relevant roles has opened the way to develop methods able to discriminate between the different ncRNA classes. Moreover, the lack of knowledge about the complete mechanisms in regulative processes, together with the development of high-throughput technologies, has required the help of bioinformatics tools in addressing biologists and clinicians with a deeper comprehension of the functional roles of ncRNAs. In this work, we introduce a new ncRNA classification tool, nRC (non-coding RNA Classifier). Our approach is based on features extraction from the ncRNA secondary structure together with a supervised classification algorithm implementing a deep learning architecture based on convolutional neural networks. We tested our approach for the classification of 13 different ncRNA classes. We obtained classification scores, using the most common statistical measures. In particular, we reach an accuracy and sensitivity score of about 74%. The proposed method outperforms other similar classification methods based on secondary structure features and machine learning algorithms, including the RNAcon tool that, to date, is the reference classifier. nRC tool is freely available as a docker image at https://hub.docker.com/r/tblab/nrc/. The source code of nRC tool is also available at https://github.com/IcarPA-TBlab/nrc.

MiR-29a: a potential therapeutic target and promising biomarker in tumors

PubMed Central

Wang, Jin-yan; Zhang, Qian; Wang, Dan-dan; Yan, Wei; Sha, Huan-huan; Zhao, Jian-hua; Yang, Su-jin; Zhang, He-da; Hou, Jun-chen; Xu, Han-zi; He, Yun-jie; Hu, Jia-hua

2017-01-01

MiRNAs, small non-coding RNA molecules, were recognized to be associated with the incidence and development of diverse neoplasms. MiRNAs were small non-coding RNAs that could regulate post-transcriptional level by binding to 3′-UTR of target mRNAs. Amongst which, miR-29a was demonstrated that it had significant impact on oncogenicity in various neoplasms through binding to critical genes which enhanced or inhibited the progression of cancers. MiR-29a participated in kinds of physiological and pathological processes, including virus replication, cell proliferation, differentiation, apoptosis, fibrosis, angiogenesis, tumorigenicity, metastasis, drug-resistance, and so on. According to its sufficient sensitivity and specificity, many studies showed that miR-29a might serve as a potential therapeutic target and promising biomarker in various tumors. In this review, we discussed the functions of miR-29a and its potential application in the diagnosis, treatment and stages of carcinoma, which could provide additional insight to develop a novel therapeutic strategy. PMID:29217524

Medicine, material science and security: the versatility of the coded-aperture approach.

PubMed

Munro, P R T; Endrizzi, M; Diemoz, P C; Hagen, C K; Szafraniec, M B; Millard, T P; Zapata, C E; Speller, R D; Olivo, A

2014-03-06

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale.

An in silico argument for mitochondrial microRNA as a determinant of primary non function in liver transplantation.

PubMed

Khorsandi, Shirin Elizabeth; Salehi, Siamak; Cortes, Miriam; Vilca-Melendez, Hector; Menon, Krishna; Srinivasan, Parthi; Prachalias, Andreas; Jassem, Wayel; Heaton, Nigel

2018-02-15

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.

Characterization of circulating transfer RNA-Derived RNA fragments in cattle

USDA-ARS?s Scientific Manuscript database

The objective was to characterize naturally occurring circulating transfer RNA-derived RNA Fragments (tRFs) in cattle. Serum from eight clinically normal adult dairy cows was collected, and small non-coding RNAs were extracted immediately after collection and sequenced by Illumina MiSeq. Sequences a...

TAS3 miR390-dependent loci in non-vascular land plants: towards a comprehensive reconstruction of the gene evolutionary history.

PubMed

Morozov, Sergey Y; Milyutina, Irina A; Erokhina, Tatiana N; Ozerova, Liudmila V; Troitsky, Alexey V; Solovyev, Andrey G

2018-01-01

Trans-acting small interfering RNAs (ta-siRNAs) are transcribed from protein non-coding genomic TAS loci and belong to a plant-specific class of endogenous small RNAs. These siRNAs have been found to regulate gene expression in most taxa including seed plants, gymnosperms, ferns and mosses. In this study, bioinformatic and experimental PCR-based approaches were used as tools to analyze TAS3 and TAS6 loci in transcriptomes and genomic DNAs from representatives of evolutionary distant non-vascular plant taxa such as Bryophyta, Marchantiophyta and Anthocerotophyta. We revealed previously undiscovered TAS3 loci in plant classes Sphagnopsida and Anthocerotopsida, as well as TAS6 loci in Bryophyta classes Tetraphidiopsida, Polytrichopsida, Andreaeopsida and Takakiopsida. These data further unveil the evolutionary pathway of the miR390-dependent TAS3 loci in land plants. We also identified charophyte alga sequences coding for SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for generation of ta-siRNAs in plants, and hypothesized that the appearance of TAS3-related sequences could take place at a very early step in evolutionary transition from charophyte algae to an earliest common ancestor of land plants.

Phylogenetic and Biochemical Studies on Stomatococcus mucilaginosus.

PubMed

Stackebrandt, E; Scheuerlein, C; Schleifer, K H

1983-01-01

The degree of relatedness of nine strains of Stomatococcus mucilaginosus (formerly classified as 'Micrococcus mucilaginosus') was investigated by deoxyribonucleic acid hybridization. We confirm that all strains are highly related. Differences in the peptidoglycan type and the cytochrome pattern between S. mucilaginosus and members of Micrococcus, together with the results of 23 S ribosomal ribonucleic acid cistron similarity studies and the analysis of the 16S ribosomal ribonucleic acid support the exclusion of this species from the genus Micrococcus and justifies its reclassification as a member of a new genus, Stomatococcus (Bergan and Kocur, 1982). Phylogenetically, S. mucilaginosus represents an independent line of descent within a broad group of Gram-positive bacteria that contains arthrobacteria, micrococci, cellulomonads, brevibacteria and microbacteria. Copyright © 1983 Gustav Fischer Verlag, Stuttgart/New York. Published by Elsevier GmbH.. All rights reserved.

Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells.

PubMed Central

Hendrick, J P; Wolin, S L; Rinke, J; Lerner, M R; Steitz, J A

1981-01-01

Small ribonucleic acid (RNA)-protein complexes precipitated by anti-Ro and anti-La antibodies from lupus patients have been examined with emphasis on their RNA components. In both ribonucleoprotein (RNP) classes, the numbers of different RNA molecules and their sequences vary between mouse and human cells. The complex mixtures of La RNAs include two previously sequenced 4.5S RNAs from mouse cells and 5S ribosomal RNA-like molecules from both mouse and human cells. All Ro and La RNAs possess 5-triphosphates. Some La RNAs have internal modifications typical of transfer RNAs. The Ro RNPs are quite stable and are localized by immunofluorescence in the cell cytoplasm, whereas the majority of the La RNPs turn over rapidly and reside in the nucleus. Despite these differences, reconstitution experiments show that the Ro particles carry the La as well as the Ro determinant. Studies using a nuclear transcription system demonstrate that most of the La RNAs are synthesized by RNA polymerase III. The possibility that the La protein(s) functions in the transcription or maturation of all RNA polymerase III transcripts is discussed. Images PMID:6180298

Identification and Classification of New Transcripts in Dorper and Small-Tailed Han Sheep Skeletal Muscle Transcriptomes.

PubMed

Chao, Tianle; Wang, Guizhi; Wang, Jianmin; Liu, Zhaohua; Ji, Zhibin; Hou, Lei; Zhang, Chunlan

2016-01-01

High-throughput mRNA sequencing enables the discovery of new transcripts and additional parts of incompletely annotated transcripts. Compared with the human and cow genomes, the reference annotation level of the sheep genome is still low. An investigation of new transcripts in sheep skeletal muscle will improve our understanding of muscle development. Therefore, applying high-throughput sequencing, two cDNA libraries from the biceps brachii of small-tailed Han sheep and Dorper sheep were constructed, and whole-transcriptome analysis was performed to determine the unknown transcript catalogue of this tissue. In this study, 40,129 transcripts were finally mapped to the sheep genome. Among them, 3,467 transcripts were determined to be unannotated in the current reference sheep genome and were defined as new transcripts. Based on protein-coding capacity prediction and comparative analysis of sequence similarity, 246 transcripts were classified as portions of unannotated genes or incompletely annotated genes. Another 1,520 transcripts were predicted with high confidence to be long non-coding RNAs. Our analysis also revealed 334 new transcripts that displayed specific expression in ruminants and uncovered a number of new transcripts without intergenus homology but with specific expression in sheep skeletal muscle. The results confirmed a complex transcript pattern of coding and non-coding RNA in sheep skeletal muscle. This study provided important information concerning the sheep genome and transcriptome annotation, which could provide a basis for further study.

Microbiological and chemical quality of ground water used as a source of public supply in southern Missouri : Phase II, April-July, 1998

USGS Publications Warehouse

Femmer, Suzanne R.

2000-01-01

The protection of public health through quality public ground-water systems is the responsibility of the U. S. Environmental Protection Agency and the State of Missouri, through the Missouri Department of Natural Resources, Public Drinking Water Program. Approximately 95 percent of the public-water supplies in Missouri use ground water as their source of drinking water through more than 3,700 public wells. Karst terrain, intensive agricultural operations, extensive numbers of on-site sewage systems, and poor well construction can lead to chemical and microbiological contamination of the contributing aquifers. Sitespecific studies and routine regulatory monitoring have produced information on the overall quality and potability of the State's public-drinking-water supplies, but little is known about the presence of viruses. The U.S. Geological Survey, in cooperation with the Missouri Department of Natural Resources, sampled 109 public-water supplies to characterize the physical, chemical, bacterial, and viral conditions in southern Missouri. During April to July 1998, these wells were sampled for nutrients, total organic carbon, optical brighteners, indicator bacteria, enteric viruses, and ribonucleic acid and somatic coli phages. These constituents indicate possible surface contamination of the sampled aquifer. Selection of the wells to be sampled depended on the age of the well (pre-1970), land use, geohydrology, and well construction. None of the physical or chemical constituents measured or analyzed exceeded Missouri's Drinking Water Standards set by the Public Drinking Water Program of the Missouri Department of Natural Resources. The majority of ammonia plus organic nitrogen, nitrite, and phosphorus concentrations were below the laboratory's minimum reporting levels. There were a greater number of detects above the minimum reporting level with respect to the nitrite plus nitrate, ammonia, orthophosphate, and total organic carbon concentrations. Analyses included comparing and contrasting the data by grouping according to well age and construction, karst type, geohydrology, soil type, and land use. There was little variation in well construction between selected wells. The results indicated several groupings of similar and dissimilar concentrations, most expected because of hydrological, physical, or land use differences. Dissolved oxygen values indicated distinct variation in the different groupings. There were significant differences in dissolved oxygen values between the secondary and non-karst areas, the Ozark confined and Ozark unconfined geohydrologic groups, and between agricultural and other land uses. In groupings by soil and geohydrology, the Missouri bootheel region differed with respect to ammonia, total organic carbon, and phosphorus when compared with the other groups. Less than 10 percent of the wells sampled tested positive for bacterial contamination. E. coli was the most frequently detected bacterium. The public wells at Monett and West Plains, Missouri, had plates with colonies too numerous to count for all three indicator bacteria. Further analyses by rRNA (ribosomal RiboNucleic Acid) hybridization techniques detennined that much of the bacteria present were from ruminant and human sources. No enteric viruses were detected in the 109 samples. Both ribonucleic acid and somatic coliphage were detected at two wells. One additional well had ribonucleic acid coliphage and another had somatic coliphage for a total of four wells with coliphage selects.

The expression of 11β-hydroxysteroid dehydrogenase type 1 and 2 in nasal polyp-derived epithelial cells and its possible contribution to glucocorticoid activation in nasal polyp.

PubMed

Kook, Jin Ho; Kim, Hyun Jin; Kim, Kyung Won; Park, Se Jin; Kim, Tae Hoon; Lim, Sae Hee; Kang, Sung Hoon; Lee, Sang Hag

2015-01-01

The actions of glucocorticoids in target tissues depend on the local metabolism of glucocorticoids catalyzed by 11β hydroxysteroid dehydrogenase (HSD) 1 and 2. Glucocorticoids are the most effective anti-inflammatory drugs in the treatment of nasal polyps. However, the mechanisms that underlie the anti-inflammatory effects are unclear. The present study analyzed the expression of 11β-HSD1, 11β-HSD2, and steroidogenic enzymes (cytochrome P450, family 11, subfamily B, polypeptide 1 [CYP11B1]; cytochrome P450, family 11, subfamily A, polypeptide 1 [CYP11A1]) in nasal polyp tissues, and endogenous cortisol levels in nasal polyp-derived epithelial cells. The expression levels and distribution pattern of 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1 were determined in nasal polyp tissues or nasal polyp-derived epithelial cells by using real-time polymerase chain reaction, Western blot, and immunohistochemistry testing. The expression levels of cortisol by using enzyme-linked immunosorbent assay were determined in cultured polyp-derived epithelial cells treated with adrenocorticotrophic hormone (ACTH), 11β-HSD1 inhibitor, or small interfering ribonucleic acid technique. The effect of glucocorticoids on the expression levels of these enzymes was investigated in cultured cells. Expressed in nasal polyp tissues and nasal polyp-derived epithelial cells were 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1. Cortisol production in cultured epithelial cells was decreased in cells treated with 11β-HSD1 small interfering ribonucleic acid or inhibitor, compared with nontreated cells. Cultured cells treated with adrenocorticotropic hormone induced increased cortisol production. 11β-HSD1 expression levels were upregulated in cells treated with glucocorticoid. Analysis of these results indicated that 11β-HSD1 expressed in polyp-derived epithelial cells may be involved in the anti-inflammatory function of glucocorticoid in the treatment of nasal polyps, which contributes to increased levels of endogenous cortisol.

Whole-genome sequencing reveals a coding non-pathogenic variant tagging a non-coding pathogenic hexanucleotide repeat expansion in C9orf72 as cause of amyotrophic lateral sclerosis.

PubMed

Herdewyn, Sarah; Zhao, Hui; Moisse, Matthieu; Race, Valérie; Matthijs, Gert; Reumers, Joke; Kusters, Benno; Schelhaas, Helenius J; van den Berg, Leonard H; Goris, An; Robberecht, Wim; Lambrechts, Diether; Van Damme, Philip

2012-06-01

Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) has a familial cause in 10% of patients. Despite significant advances in the genetics of the disease, many families remain unexplained. We performed whole-genome sequencing in five family members from a pedigree with autosomal-dominant classical ALS. A family-based elimination approach was used to identify novel coding variants segregating with the disease. This list of variants was effectively shortened by genotyping these variants in 2 additional unaffected family members and 1500 unrelated population-specific controls. A novel rare coding variant in SPAG8 on chromosome 9p13.3 segregated with the disease and was not observed in controls. Mutations in SPAG8 were not encountered in 34 other unexplained ALS pedigrees, including 1 with linkage to chromosome 9p13.2-23.3. The shared haplotype containing the SPAG8 variant in this small pedigree was 22.7 Mb and overlapped with the core 9p21 linkage locus for ALS and frontotemporal dementia. Based on differences in coverage depth of known variable tandem repeat regions between affected and non-affected family members, the shared haplotype was found to contain an expanded hexanucleotide (GGGGCC)(n) repeat in C9orf72 in the affected members. Our results demonstrate that rare coding variants identified by whole-genome sequencing can tag a shared haplotype containing a non-coding pathogenic mutation and that changes in coverage depth can be used to reveal tandem repeat expansions. It also confirms (GGGGCC)n repeat expansions in C9orf72 as a cause of familial ALS.

microRNAs of parasites: current status and future perspectives

USDA-ARS?s Scientific Manuscript database

MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs regulating gene expression in eukaryotes at the post-transcriptional level. The complex life cycles of parasites may require the ability to respond to environmental and developmental signals through miRNA-mediated gene expression. Ov...

Fire related hazards of cables: The Canadian position development of fire resistant inside wiring cable

NASA Astrophysics Data System (ADS)

Hartley, M. D.; Jaques, R. E.

1986-11-01

The Canadian Electrical Code and the National Building Code in Canada recognize only two designations in regards to fire resistance of cables; cables for use in combustible (residential) buildings and cables for use in non-combustible buildings. The Test standard for cables for non-combustible buildings resembles IEEE-383. However, it is more severe; particularly for small nonarmoured cables such as Inside Wiring Cable. This forthcoming requirement has necessitated material and product development. Although an Inside Wiring cable modification of both insulation and jacket was undertaken, the large volume fraction of combustible material in the jacket vis a vis the insulation made it the area of greatest impact. The paper outlines the development and its effect on cable performance.

Genetics Home Reference: Pol III-related leukodystrophy

MedlinePlus

... two largest parts (subunits) of an enzyme called RNA polymerase III. This enzyme is involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. The RNA polymerase ...

Micro-ribonucleic acid-binding site variants of type 2 diabetes candidate loci predispose to gestational diabetes mellitus in Chinese Han women.

PubMed

Wang, Xiaojing; Li, Wei; Ma, Liangkun; Ping, Fan; Liu, Juntao; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2018-01-20

Emerging evidence has suggested that the genetic background of gestational diabetes mellitus (GDM) was analogous to type 2 diabetes mellitus. In contrast to type 2 diabetes mellitus, the genetic studies for GDM were limited. Accordingly, the aim of the present study was to extensively explore the influence of micro-ribonucleic acid-binding single-nucleotide polymorphisms (SNPs) in type 2 diabetes mellitus candidate loci on GDM susceptibility in Chinese. A total of 839 GDM patients and 900 controls were enrolled. Six micro-ribonucleic acid-binding SNPs were selected from 30 type 2 diabetes mellitus susceptibility loci and genotyped using TaqMan allelic discrimination assays. The minor allele of three SNPs, PAX4 rs712699 (OR 1.366, 95% confidence interval 1.021-1.828, P = 0.036), KCNB1 rs1051295 (OR 1.579, 95% confidence interval 1.172-2.128, P = 0.003) and MFN2 rs1042842 (OR 1.398, 95% confidence interval 1.050-1.862, P = 0.022) were identified to significantly confer higher a risk of GDM in the additive model. The association between rs1051295 and increased fasting plasma glucose (b = 0.006, P = 0.008), 3-h oral glucose tolerance test plasma glucose (b = 0.058, P = 0.025) and homeostatic model assessment of insulin resistance (b = 0.065, P = 0.017) was also shown. Rs1042842 was correlated with higher 3-h oral glucose tolerance test plasma glucose (b = 0.056, P = 0.028). However, no significant correlation between the other included SNPs (LPIN1 rs1050800, VPS26A rs1802295 and NLRP3 rs10802502) and GDM susceptibility were observed. The present findings showed that micro-ribonucleic acid-binding SNPs in type 2 diabetes mellitus candidate loci were also associated with GDM susceptibility, which further highlighted the similar genetic basis underlying GDM and type 2 diabetes mellitus. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

A validated non-linear Kelvin-Helmholtz benchmark for numerical hydrodynamics

NASA Astrophysics Data System (ADS)

Lecoanet, D.; McCourt, M.; Quataert, E.; Burns, K. J.; Vasil, G. M.; Oishi, J. S.; Brown, B. P.; Stone, J. M.; O'Leary, R. M.

2016-02-01

The non-linear evolution of the Kelvin-Helmholtz instability is a popular test for code verification. To date, most Kelvin-Helmholtz problems discussed in the literature are ill-posed: they do not converge to any single solution with increasing resolution. This precludes comparisons among different codes and severely limits the utility of the Kelvin-Helmholtz instability as a test problem. The lack of a reference solution has led various authors to assert the accuracy of their simulations based on ad hoc proxies, e.g. the existence of small-scale structures. This paper proposes well-posed two-dimensional Kelvin-Helmholtz problems with smooth initial conditions and explicit diffusion. We show that in many cases numerical errors/noise can seed spurious small-scale structure in Kelvin-Helmholtz problems. We demonstrate convergence to a reference solution using both ATHENA, a Godunov code, and DEDALUS, a pseudo-spectral code. Problems with constant initial density throughout the domain are relatively straightforward for both codes. However, problems with an initial density jump (which are the norm in astrophysical systems) exhibit rich behaviour and are more computationally challenging. In the latter case, ATHENA simulations are prone to an instability of the inner rolled-up vortex; this instability is seeded by grid-scale errors introduced by the algorithm, and disappears as resolution increases. Both ATHENA and DEDALUS exhibit late-time chaos. Inviscid simulations are riddled with extremely vigorous secondary instabilities which induce more mixing than simulations with explicit diffusion. Our results highlight the importance of running well-posed test problems with demonstrated convergence to a reference solution. To facilitate future comparisons, we include as supplementary material the resolved, converged solutions to the Kelvin-Helmholtz problems in this paper in machine-readable form.

Rpl13a small nucleolar RNAs regulate systemic glucose metabolism

PubMed Central

Lee, Jiyeon; Harris, Alexis N.; Holley, Christopher L.; Mahadevan, Jana; Pyles, Kelly D.; Lavagnino, Zeno; Scherrer, David E.; Fujiwara, Hideji; Sidhu, Rohini; Zhang, Jessie; Huang, Stanley Ching-Cheng; Piston, David W.; Remedi, Maria S.; Urano, Fumihiko; Ory, Daniel S.

2016-01-01

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the physiological contributions of these small RNAs are largely unknown. Here, we selectively deleted four snoRNAs encoded within the introns of the ribosomal protein L13a (Rpl13a) locus in a mouse model. Loss of Rpl13a snoRNAs altered mitochondrial metabolism and lowered reactive oxygen species tone, leading to increased glucose-stimulated insulin secretion from pancreatic islets and enhanced systemic glucose tolerance. Islets from mice lacking Rpl13a snoRNAs demonstrated blunted oxidative stress responses. Furthermore, these mice were protected against diabetogenic stimuli that cause oxidative stress damage to islets. Our study illuminates a previously unrecognized role for snoRNAs in metabolic regulation. PMID:27820699

Selective Methylation: an Incorrect Hypothesis

PubMed Central

Shugart, Lee

1976-01-01

“Selective methylation,” a hypothesis proposed to explain the discrepancy found in the degree of methyl deficiency of transfer ribonucleic acid, cannot be explained on the basis of some biological phenomenon. PMID:770445

Analog system for computing sparse codes

DOEpatents

Rozell, Christopher John; Johnson, Don Herrick; Baraniuk, Richard Gordon; Olshausen, Bruno A.; Ortman, Robert Lowell

2010-08-24

A parallel dynamical system for computing sparse representations of data, i.e., where the data can be fully represented in terms of a small number of non-zero code elements, and for reconstructing compressively sensed images. The system is based on the principles of thresholding and local competition that solves a family of sparse approximation problems corresponding to various sparsity metrics. The system utilizes Locally Competitive Algorithms (LCAs), nodes in a population continually compete with neighboring units using (usually one-way) lateral inhibition to calculate coefficients representing an input in an over complete dictionary.

A Transgenic Transcription Factor (TaDREB3) in Barley Affects the Expression of MicroRNAs and Other Small Non-Coding RNAs

PubMed Central

Hackenberg, Michael; Shi, Bu-Jun; Gustafson, Perry; Langridge, Peter

2012-01-01

Transcription factors (TFs), microRNAs (miRNAs), small interfering RNAs (siRNAs) and other functional non-coding small RNAs (sRNAs) are important gene regulators. Comparison of sRNA expression profiles between transgenic barley over-expressing a drought tolerant TF (TaDREB3) and non-transgenic control barley revealed many group-specific sRNAs. In addition, 42% of the shared sRNAs were differentially expressed between the two groups (|log2| >1). Furthermore, TaDREB3-derived sRNAs were only detected in transgenic barley despite the existence of homologous genes in non-transgenic barley. These results demonstrate that the TF strongly affects the expression of sRNAs and siRNAs could in turn affect the TF stability. The TF also affects size distribution and abundance of sRNAs including miRNAs. About half of the sRNAs in each group were derived from chloroplast. A sRNA derived from tRNA-His(GUG) encoded by the chloroplast genome is the most abundant sRNA, accounting for 42.2% of the total sRNAs in transgenic barley and 28.9% in non-transgenic barley. This sRNA, which targets a gene (TC245676) involved in biological processes, was only present in barley leaves but not roots. 124 and 136 miRNAs were detected in transgenic and non-transgenic barley, respectively. miR156 was the most abundant miRNA and up-regulated in transgenic barley, while miR168 was the most abundant miRNA and up-regulated in non-transgenic barley. Eight out of 20 predicted novel miRNAs were differentially expressed between the two groups. All the predicted novel miRNA targets were validated using a degradome library. Our data provide an insight into the effect of TF on the expression of sRNAs in barley. PMID:22870277

The development of fixed-ratio performance under the influence of ribonucleic acid12

PubMed Central

Gott, C. Thomas; Weiss, Bernard

1972-01-01

The transition from fixed-ratio 1 performance (every response reinforced) to fixed-ratio 30 performance (every thirtieth response reinforced) was studied in nine pigeons. These were divided into three treatment groups given daily oral doses of saline, or 250 mg/kg/day or 500 mg/kg/day of yeast ribonucleic acid. Detailed computer-assisted analyses of how fixed-ratio behavior develops revealed the following typical sequence. After the transition, the first few ratios typically were emitted without long interresponse times within the ratio. Steady responding then ceased, and numerous long interresponse times occurred, with no systematic relationship to ordinal position within the ratio. Gradually, a new pattern evolved, characterized by a consistently long post-reinforcement time, a border region of the next few interresponse times within which the mean interresponse time monotonically decreased, and short interresponse times within the last 80% of the ratio. Long interresponse times were eliminated from this last section of the ratio without regard to proximity to reinforcement. Various analytical procedures suggested that the final pattern can be conceived, in part, as the shaping of a reliable response topography. The group of three pigeons given 250 mg/kg/day of yeast ribonucleic acid responded at higher rates than the saline and 500 mg/kg/day groups. The latter group, in contrast to the saline and lower dose groups, which continued to increase their rates, reached a rate asymptote very early. PMID:4574711

Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope

NASA Astrophysics Data System (ADS)

Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R.; Gambhir, Sanjiv S.; Kino, Gordon S.; Solgaard, Olav; Kaspar, Roger L.; Contag, Christopher H.

2010-05-01

Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

Genome-wide identification of microRNAs in pomegranate (Punica granatum L.) by high-throughput sequencing

USDA-ARS?s Scientific Manuscript database

Background: MicroRNAs (miRNAs), a class of small non-coding endogenous RNAs that regulate gene expression post-transcriptionally, play multiple key roles in plant growth and development and in biotic and abiotic stress response. Knowledge and roles of miRNAs in pomegranate fruit development have not...

NEAT1 Scaffolds RNA Binding Proteins and the Microprocessor to Globally Enhance Pri-miRNA Processing

PubMed Central

Jiang, Li; Shao, Changwei; Wu, Qi-Jia; Chen, Geng; Zhou, Jie; Yang, Bo; Li, Hairi; Gou, Lan-Tao; Zhang, Yi; Wang, Yangming; Yeo, Gene W.; Zhou, Yu; Fu, Xiang-Dong

2018-01-01

Summary MicroRNA biogenesis is known to be modulated by a variety of RNA binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. We herein report that the RNA binding NONO/PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha/DGCR8 Microprocessor. Because NONO/PSF are key components of paraspeckles organized by the lncRNA NEAT1, we further demonstrate that NEAT1 also has a profound effect on global pri-miRNA processing. Mechanistic dissection reveals that NEAT1 broadly interacts with NONO/PSF as well as many other RBPs, and that multiple RNA segments in NEAT1, including a “pseudo pri-miRNA” near its 3′ end, help attract the Microprocessor. These findings suggest a bird nest model for a large non-coding RNA to orchestrate efficient processing of almost an entire class of small non-coding RNAs in the nucleus. PMID:28846091

Emerging Roles of Small Epstein-Barr Virus Derived Non-Coding RNAs in Epithelial Malignancy

PubMed Central

Lung, Raymond Wai-Ming; Tong, Joanna Hung-Man; To, Ka-Fai

2013-01-01

Latent Epstein-Barr virus (EBV) infection is an etiological factor in the progression of several human epithelial malignancies such as nasopharyngeal carcinoma (NPC) and a subset of gastric carcinoma. Reports have shown that EBV produces several viral oncoproteins, yet their pathological roles in carcinogenesis are not fully elucidated. Studies on the recently discovered of EBV-encoded microRNAs (ebv-miRNAs) showed that these small molecules function as post-transcriptional gene regulators and may play a role in the carcinogenesis process. In NPC and EBV positive gastric carcinoma (EBVaGC), 22 viral miRNAs which are located in the long alternative splicing EBV transcripts, named BamH1 A rightward transcripts (BARTs), are abundantly expressed. The importance of several miR-BARTs in carcinogenesis has recently been demonstrated. These novel findings enhance our understanding of the oncogenic properties of EBV and may lead to a more effective design of therapeutic regimens to combat EBV-associated malignancies. This article will review the pathological roles of miR-BARTs in modulating the expression of cancer-related genes in both host and viral genomes. The expression of other small non-coding RNAs in NPC and the expression pattern of miR-BARTs in rare EBV-associated epithelial cancers will also be discussed. PMID:23979421

Diatomite biosilica nanocarriers for siRNA transport inside cancer cells.

PubMed

Rea, Ilaria; Martucci, Nicola M; De Stefano, Luca; Ruggiero, Immacolata; Terracciano, Monica; Dardano, Principia; Migliaccio, Nunzia; Arcari, Paolo; Taté, Rosarita; Rendina, Ivo; Lamberti, Annalisa

2014-12-01

Diatomite is a natural porous biomaterial of sedimentary origin, formed by fragments of diatom siliceous skeletons, called "frustules". Due to large availability in many areas of the world, chemical stability, and non-toxicity, these fossil structures have been widespread used in lot of industrial applications, such as food production, water extracting agent, production of cosmetics and pharmaceutics. However, diatomite is surprisingly still rarely used in biomedical applications. In this work, we exploit diatomite nanoparticles for small interfering ribonucleic acid (siRNA) transport inside human epidermoid cancer cells (H1355). Morphology and composition of diatomite microfrustules (average size lower than 40μm) are investigated by scanning electron microscopy equipped by energy dispersive X-ray spectroscopy, Fourier transform infrared analysis, and photoluminescence measurements. Nanometric porous particles (average size lower than 450nm) are obtained by mechanical crushing, sonication, and filtering of micrometric frustules. siRNA bioconjugation is performed on both micrometric and nanometric fragments by silanization. In-vitro experiments show very low toxicity on exposure of the cells to diatomite nanoparticle concentration up to 300μg/ml for 72h. Confocal microscopy imaging performed on cancer cells incubated with siRNA conjugated nanoparticles demonstrates a cytoplasmatic localization of vectors. Gene silencing by delivered siRNA is also demonstrated. Our studies endorse diatomite nanoparticles as non-toxic nanocarriers for siRNA transport in cancer cells. siRNA is a powerful molecular tool for cancer treatment but its delivery is inefficient due to the difficulty to penetrate the cell membrane. siRNA-diatomite nanoconjugate may be well suited for delivery of therapeutic to cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Small Open Reading Frames, Non-Coding RNAs and Repetitive Elements in Bradyrhizobium japonicum USDA 110

PubMed Central

Hahn, Julia; Tsoy, Olga V.; Thalmann, Sebastian; Čuklina, Jelena; Gelfand, Mikhail S.

2016-01-01

Small open reading frames (sORFs) and genes for non-coding RNAs are poorly investigated components of most genomes. Our analysis of 1391 ORFs recently annotated in the soybean symbiont Bradyrhizobium japonicum USDA 110 revealed that 78% of them contain less than 80 codons. Twenty-one of these sORFs are conserved in or outside Alphaproteobacteria and most of them are similar to genes found in transposable elements, in line with their broad distribution. Stabilizing selection was demonstrated for sORFs with proteomic evidence and bll1319_ISGA which is conserved at the nucleotide level in 16 alphaproteobacterial species, 79 species from other taxa and 49 other Proteobacteria. Further we used Northern blot hybridization to validate ten small RNAs (BjsR1 to BjsR10) belonging to new RNA families. We found that BjsR1 and BjsR3 have homologs outside the genus Bradyrhizobium, and BjsR5, BjsR6, BjsR7, and BjsR10 have up to four imperfect copies in Bradyrhizobium genomes. BjsR8, BjsR9, and BjsR10 are present exclusively in nodules, while the other sRNAs are also expressed in liquid cultures. We also found that the level of BjsR4 decreases after exposure to tellurite and iron, and this down-regulation contributes to survival under high iron conditions. Analysis of additional small RNAs overlapping with 3’-UTRs revealed two new repetitive elements named Br-REP1 and Br-REP2. These REP elements may play roles in the genomic plasticity and gene regulation and could be useful for strain identification by PCR-fingerprinting. Furthermore, we studied two potential toxin genes in the symbiotic island and confirmed toxicity of the yhaV homolog bll1687 but not of the newly annotated higB homolog blr0229_ISGA in E. coli. Finally, we revealed transcription interference resulting in an antisense RNA complementary to blr1853, a gene induced in symbiosis. The presented results expand our knowledge on sORFs, non-coding RNAs and repetitive elements in B. japonicum and related bacteria. PMID:27788207

Flavivirus RNAi suppression: decoding non-coding RNA.

PubMed

Pijlman, Gorben P

2014-08-01

Flaviviruses are important human pathogens that are transmitted by invertebrate vectors, mostly mosquitoes and ticks. During replication in their vector, flaviviruses are subject to a potent innate immune response known as antiviral RNA interference (RNAi). This defense mechanism is associated with the production of small interfering (si)RNA that lead to degradation of viral RNA. To what extent flaviviruses would benefit from counteracting antiviral RNAi is subject of debate. Here, the experimental evidence to suggest the existence of flavivirus RNAi suppressors is discussed. I will highlight the putative role of non-coding, subgenomic flavivirus RNA in suppression of RNAi in insect and mammalian cells. Novel insights from ongoing research will reveal how arthropod-borne viruses modulate innate immunity including antiviral RNAi. Copyright © 2014 Elsevier B.V. All rights reserved.

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations.

PubMed

Gormley, Matthew; Ona, Katherine; Kapidzic, Mirhan; Garrido-Gomez, Tamara; Zdravkovic, Tamara; Fisher, Susan J

2017-08-01

The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of non-protein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-type-specific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy complication. Gene ontology analysis of the syncytiotrophoblast data highlighted the dysregulation of immune functions, morphogenesis, transport, and responses to vascular endothelial growth factor and progesterone. The invasive cytotrophoblast data provided evidence of alterations in cellular movement, which is consistent with the shallow invasion often associated with severe preeclampsia. Other dysregulated pathways included immune, lipid, oxygen, and transforming growth factor-beta responses. The data for endovascular cytotrophoblasts showed disordered metabolism, signaling, and vascular development. Additionally, the transcriptional data revealed the differential expression in severe preeclampsia of 2 classes of non-coding RNAs: long non-coding RNAs and small nucleolar RNAs. The long non-coding RNA, urothelial cancer associated 1, was the most highly up-regulated in this class. In situ hybridization confirmed severe preeclampsia-associated expression in syncytiotrophoblasts. The small nucleolar RNAs, which chemically modify RNA structure, also correlated with severe preeclampsia. Thus, we enumerated Cajal body foci, sites of small nucleolar RNA activity, in primary cytotrophoblasts that were isolated from control and severe preeclampsia placentas. In severe preeclampsia, cytotrophoblasts had approximately double the number of these foci as the control samples. A laser microdissection approach enabled the identification of novel messenger RNAs and non-coding RNAs that were misexpressed by various trophoblast subpopulations in severe preeclampsia. The results suggested new avenues of investigation, in particular, the roles of PRG2, Kell blood group determinants, and urothelial cancer associated 1 in syncytiotrophoblast diseases. Additionally, many of the newly identified dysregulated molecules might have clinical utility as biomarkers of severe preeclampsia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Downregulation of BRAF-activated non-protein coding RNA in patients with hepatitis B virus-associated hepatocellular carcinoma.

PubMed

Zhao, Na-Na; Wang, Cheng; Lai, Cheng-Cai; Cheng, Si-Jie; Yan, Jin; Hong, Zhi-Xian; Yu, Lin-Xiang; Zhu, Zhen-Yu; Zhang, Pei-Rui; Wang, Zhao-Hai; Wang, Xi-Liang; Zhang, Shao-Geng; Yang, Peng-Hui

2018-05-01

Long non-coding RNAs (lncRNAs) have been investigated as a novel class of regulators of cellular processes, including cell growth, apoptosis and carcinogenesis. lncRNA BRAF-activated non-protein coding RNA (BANCR) has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including papillary thyroid carcinoma, melanoma, non-small cell lung cancer and colorectal cancer. However, the expression profiles and biological relevance of lncRNA BANCR in hepatocellular carcinoma (HCC) has not yet been reported. In the present study, the expression level of BANCR in tumor tissues and para-cancerous tissues was determined by reverse transcription-quantitative polymerase chain reaction in patients with hepatitis B virus (HBV)-associated HCC, and its association with clinicopathological characteristics of patients was analyzed. The results demonstrated that the expression level of BANCR was significantly reduced in tumor tissues in comparison with in para-cancerous tissues (P<0.001). Furthermore, the present study demonstrated that BANCR expression level was closely associated with serum α-fetoprotein levels (P<0.01) and HCC tumor number (P<0.05). To the best of our knowledge, these results revealed for the first time that BANCR downregulated in patients with HBV-associated HCC and BANCR expression level may be a potential valuable diagnosis and therapeutic biomarker in HCC.

TAS3 miR390-dependent loci in non-vascular land plants: towards a comprehensive reconstruction of the gene evolutionary history

PubMed Central

Milyutina, Irina A.; Erokhina, Tatiana N.; Ozerova, Liudmila V.; Troitsky, Alexey V.; Solovyev, Andrey G.

2018-01-01

Trans-acting small interfering RNAs (ta-siRNAs) are transcribed from protein non-coding genomic TAS loci and belong to a plant-specific class of endogenous small RNAs. These siRNAs have been found to regulate gene expression in most taxa including seed plants, gymnosperms, ferns and mosses. In this study, bioinformatic and experimental PCR-based approaches were used as tools to analyze TAS3 and TAS6 loci in transcriptomes and genomic DNAs from representatives of evolutionary distant non-vascular plant taxa such as Bryophyta, Marchantiophyta and Anthocerotophyta. We revealed previously undiscovered TAS3 loci in plant classes Sphagnopsida and Anthocerotopsida, as well as TAS6 loci in Bryophyta classes Tetraphidiopsida, Polytrichopsida, Andreaeopsida and Takakiopsida. These data further unveil the evolutionary pathway of the miR390-dependent TAS3 loci in land plants. We also identified charophyte alga sequences coding for SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for generation of ta-siRNAs in plants, and hypothesized that the appearance of TAS3-related sequences could take place at a very early step in evolutionary transition from charophyte algae to an earliest common ancestor of land plants. PMID:29682420

MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer.

PubMed

Zhou, Qun; Huang, Shao-Xin; Zhang, Feng; Li, Shu-Jun; Liu, Cong; Xi, Yong-Yong; Wang, Liang; Wang, Xin; He, Qi-Qiang; Sun, Cheng-Cao; Li, De-Jia

2017-12-01

Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase. A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC. MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC. © 2017 John Wiley & Sons Ltd.

Representation mutations from standard genetic codes

NASA Astrophysics Data System (ADS)

Aisah, I.; Suyudi, M.; Carnia, E.; Suhendi; Supriatna, A. K.

2018-03-01

Graph is widely used in everyday life especially to describe model problem and describe it concretely and clearly. In addition graph is also used to facilitate solve various kinds of problems that are difficult to be solved by calculation. In Biology, graph can be used to describe the process of protein synthesis in DNA. Protein has an important role for DNA (deoxyribonucleic acid) or RNA (ribonucleic acid). Proteins are composed of amino acids. In this study, amino acids are related to genetics, especially the genetic code. The genetic code is also known as the triplet or codon code which is a three-letter arrangement of DNA nitrogen base. The bases are adenine (A), thymine (T), guanine (G) and cytosine (C). While on RNA thymine (T) is replaced with Urasil (U). The set of all Nitrogen bases in RNA is denoted by N = {C U, A, G}. This codon works at the time of protein synthesis inside the cell. This codon also encodes the stop signal as a sign of the stop of protein synthesis process. This paper will examine the process of protein synthesis through mathematical studies and present it in three-dimensional space or graph. The study begins by analysing the set of all codons denoted by NNN such that to obtain geometric representations. At this stage there is a matching between the sets of all nitrogen bases N with Z 2 × Z 2; C=(\\overline{0},\\overline{0}),{{U}}=(\\overline{0},\\overline{1}),{{A}}=(\\overline{1},\\overline{0}),{{G}}=(\\overline{1},\\overline{1}). By matching the algebraic structure will be obtained such as group, group Klein-4,Quotien group etc. With the help of Geogebra software, the set of all codons denoted by NNN can be presented in a three-dimensional space as a multicube NNN and also can be represented as a graph, so that can easily see relationship between the codon.

Low-dose exposure to bisphenols A, F and S of human primary adipocyte impacts coding and non-coding RNA profiles

PubMed Central

Leloire, Audrey; Dhennin, Véronique; Coumoul, Xavier; Yengo, Loïc; Froguel, Philippe

2017-01-01

Bisphenol A (BPA) exposure has been suspected to be associated with deleterious effects on health including obesity and metabolically-linked diseases. Although bisphenols F (BPF) and S (BPS) are BPA structural analogs commonly used in many marketed products as a replacement for BPA, only sparse toxicological data are available yet. Our objective was to comprehensively characterize bisphenols gene targets in a human primary adipocyte model, in order to determine whether they may induce cellular dysfunction, using chronic exposure at two concentrations: a “low-dose” similar to the dose usually encountered in human biological fluids and a higher dose. Therefore, BPA, BPF and BPS have been added at 10 nM or 10 μM during the differentiation of human primary adipocytes from subcutaneous fat of three non-diabetic Caucasian female patients. Gene expression (mRNA/lncRNA) arrays and microRNA arrays, have been used to assess coding and non-coding RNA changes. We detected significantly deregulated mRNA/lncRNA and miRNA at low and high doses. Enrichment in “cancer” and “organismal injury and abnormalities” related pathways was found in response to the three products. Some long intergenic non-coding RNAs and small nucleolar RNAs were differentially expressed suggesting that bisphenols may also activate multiple cellular processes and epigenetic modifications. The analysis of upstream regulators of deregulated genes highlighted hormones or hormone-like chemicals suggesting that BPS and BPF can be suspected to interfere, just like BPA, with hormonal regulation and have to be considered as endocrine disruptors. All these results suggest that as BPA, its substitutes BPS and BPF should be used with the same restrictions. PMID:28628672

The Unexpected Tuners: Are LncRNAs Regulating Host Translation during Infections?

PubMed Central

Knap, Primoz; Tebaldi, Toma; Di Leva, Francesca; Biagioli, Marta; Dalla Serra, Mauro; Viero, Gabriella

2017-01-01

Pathogenic bacteria produce powerful virulent factors, such as pore-forming toxins, that promote their survival and cause serious damage to the host. Host cells reply to membrane stresses and ionic imbalance by modifying gene expression at the epigenetic, transcriptional and translational level, to recover from the toxin attack. The fact that the majority of the human transcriptome encodes for non-coding RNAs (ncRNAs) raises the question: do host cells deploy non-coding transcripts to rapidly control the most energy-consuming process in cells—i.e., host translation—to counteract the infection? Here, we discuss the intriguing possibility that membrane-damaging toxins induce, in the host, the expression of toxin-specific long non-coding RNAs (lncRNAs), which act as sponges for other molecules, encoding small peptides or binding target mRNAs to depress their translation efficiency. Unravelling the function of host-produced lncRNAs upon bacterial infection or membrane damage requires an improved understanding of host lncRNA expression patterns, their association with polysomes and their function during this stress. This field of investigation holds a unique opportunity to reveal unpredicted scenarios and novel approaches to counteract antibiotic-resistant infections. PMID:29469820

Introducing Molecular Biology to Environmental Engineers through Development of a New Course.

ERIC Educational Resources Information Center

Oerther, Daniel B.

2002-01-01

Introduces a molecular biology course designed for environmental engineering majors using 16S ribosomal ribonucleic acid-targeted technology that allows students to identify and study microorganisms in bioreactor environments. (Contains 17 references.) (YDS)

5S ribosomal ribonucleic acid sequences in Bacteroides and Fusobacterium: evolutionary relationships within these genera and among eubacteria in general

NASA Technical Reports Server (NTRS)

Van den Eynde, H.; De Baere, R.; Shah, H. N.; Gharbia, S. E.; Fox, G. E.; Michalik, J.; Van de Peer, Y.; De Wachter, R.

1989-01-01

The 5S ribosomal ribonucleic acid (rRNA) sequences were determined for Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides capillosus, Bacteroides veroralis, Porphyromonas gingivalis, Anaerorhabdus furcosus, Fusobacterium nucleatum, Fusobacterium mortiferum, and Fusobacterium varium. A dendrogram constructed by a clustering algorithm from these sequences, which were aligned with all other hitherto known eubacterial 5S rRNA sequences, showed differences as well as similarities with respect to results derived from 16S rRNA analyses. In the 5S rRNA dendrogram, Bacteroides clustered together with Cytophaga and Fusobacterium, as in 16S rRNA analyses. Intraphylum relationships deduced from 5S rRNAs suggested that Bacteroides is specifically related to Cytophaga rather than to Fusobacterium, as was suggested by 16S rRNA analyses. Previous taxonomic considerations concerning the genus Bacteroides, based on biochemical and physiological data, were confirmed by the 5S rRNA sequence analysis.

Roles of small RNAs in the immune defense mechanisms of crustaceans.

PubMed

He, Yaodong; Ju, Chenyu; Zhang, Xiaobo

2015-12-01

Small RNAs, 21-24 nucleotides in length, are non-coding RNAs found in most multicellular organisms, as well as in some viruses. There are three main types of small RNAs including microRNA (miRNA), small-interfering RNA (siRNA), and piwi-interacting RNA (piRNA). Small RNAs play key roles in the genetic regulation of eukaryotes; at least 50% of all eukaryote genes are the targets of small RNAs. In recent years, studies have shown that some unique small RNAs are involved in the immune response of crustaceans, leading to lower or higher immune responses to infections and diseases. SiRNAs could be used as therapy for virus infection. In this review, we provide an overview of the diverse roles of small RNAs in the immune defense mechanisms of crustaceans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Finite element modelling of non-linear magnetic circuits using Cosmic NASTRAN

NASA Technical Reports Server (NTRS)

Sheerer, T. J.

1986-01-01

The general purpose Finite Element Program COSMIC NASTRAN currently has the ability to model magnetic circuits with constant permeablilities. An approach was developed which, through small modifications to the program, allows modelling of non-linear magnetic devices including soft magnetic materials, permanent magnets and coils. Use of the NASTRAN code resulted in output which can be used for subsequent mechanical analysis using a variation of the same computer model. Test problems were found to produce theoretically verifiable results.

Enhancing Scalability and Efficiency of the TOUGH2_MP for LinuxClusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Keni; Wu, Yu-Shu

2006-04-17

TOUGH2{_}MP, the parallel version TOUGH2 code, has been enhanced by implementing more efficient communication schemes. This enhancement is achieved through reducing the amount of small-size messages and the volume of large messages. The message exchange speed is further improved by using non-blocking communications for both linear and nonlinear iterations. In addition, we have modified the AZTEC parallel linear-equation solver to nonblocking communication. Through the improvement of code structuring and bug fixing, the new version code is now more stable, while demonstrating similar or even better nonlinear iteration converging speed than the original TOUGH2 code. As a result, the new versionmore » of TOUGH2{_}MP is improved significantly in its efficiency. In this paper, the scalability and efficiency of the parallel code are demonstrated by solving two large-scale problems. The testing results indicate that speedup of the code may depend on both problem size and complexity. In general, the code has excellent scalability in memory requirement as well as computing time.« less

Uptake of dietary milk microRNAs by adult humans: Rules for the game of hide and seek

USDA-ARS?s Scientific Manuscript database

Milk producers recently used a social media campaign to build public confidence in the health benefits of their product; however, it is not clear why they did not tout the abundant microRNAs (miRNAs), small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation o...

Bioinformatics of prokaryotic RNAs

PubMed Central

Backofen, Rolf; Amman, Fabian; Costa, Fabrizio; Findeiß, Sven; Richter, Andreas S; Stadler, Peter F

2014-01-01

The genome of most prokaryotes gives rise to surprisingly complex transcriptomes, comprising not only protein-coding mRNAs, often organized as operons, but also harbors dozens or even hundreds of highly structured small regulatory RNAs and unexpectedly large levels of anti-sense transcripts. Comprehensive surveys of prokaryotic transcriptomes and the need to characterize also their non-coding components is heavily dependent on computational methods and workflows, many of which have been developed or at least adapted specifically for the use with bacterial and archaeal data. This review provides an overview on the state-of-the-art of RNA bioinformatics focusing on applications to prokaryotes. PMID:24755880

Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for highly accurate CNV and SNP/INDEL detection.

PubMed

Alvarado, David M; Yang, Ping; Druley, Todd E; Lovett, Michael; Gurnett, Christina A

2014-06-01

Despite declining sequencing costs, few methods are available for cost-effective single-nucleotide polymorphism (SNP), insertion/deletion (INDEL) and copy number variation (CNV) discovery in a single assay. Commercially available methods require a high investment to a specific region and are only cost-effective for large samples. Here, we introduce a novel, flexible approach for multiplexed targeted sequencing and CNV analysis of large genomic regions called multiplexed direct genomic selection (MDiGS). MDiGS combines biotinylated bacterial artificial chromosome (BAC) capture and multiplexed pooled capture for SNP/INDEL and CNV detection of 96 multiplexed samples on a single MiSeq run. MDiGS is advantageous over other methods for CNV detection because pooled sample capture and hybridization to large contiguous BAC baits reduces sample and probe hybridization variability inherent in other methods. We performed MDiGS capture for three chromosomal regions consisting of ∼ 550 kb of coding and non-coding sequence with DNA from 253 patients with congenital lower limb disorders. PITX1 nonsense and HOXC11 S191F missense mutations were identified that segregate in clubfoot families. Using a novel pooled-capture reference strategy, we identified recurrent chromosome chr17q23.1q23.2 duplications and small HOXC 5' cluster deletions (51 kb and 12 kb). Given the current interest in coding and non-coding variants in human disease, MDiGS fulfills a niche for comprehensive and low-cost evaluation of CNVs, coding, and non-coding variants across candidate regions of interest. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

New insights into the molecular mechanism of Boletus edulis ribonucleic acid fraction (BE3) concerning antiproliferative activity on human colon cancer cells.

PubMed

Lemieszek, Marta Kinga; Ribeiro, Miguel; Marques, Guilhermina; Nunes, Fernando Milheiro; Pożarowski, Piotr; Rzeski, Wojciech

2017-05-24

One of the relatively new and promising strategies of cancer treatment is chemoprevention, which involves the use of natural or synthetic compounds to block, inhibit or reverse carcinogenesis. A valuable and still untapped source of chemopreventive compounds seems to be edible mushrooms belonging to higher Basidiomycetes. Boletus edulis biopolymers extracted with hot water and purified by anion-exchange chromatography showed antiproliferative activity in colon cancer cells, but only fraction BE3, mostly composed of ribonucleic acids, was able to inhibit DNA synthesis in HT-29 cells. The present work aims to elucidate the molecular mechanism of this Boletus edulis ribonucleic acid fraction and in this sense flow cytometry and western blotting were applied to cell cycle analysis in HT-29 cells. We found that the antiproliferative ability of fraction BE3 observed in HT-29 cells was associated with the modulation of expression of cell cycle regulatory proteins (Cyclin D1, Cyclin A, p21 and p27) leading to cell accumulation in the S phase of the cell cycle. Furthermore, the BE3 fraction showed effective silencing of the signal transduction in an MAPK/Erk pathway in HT-29 and LS180 colon cancer cell lines. Thus, the previously and currently obtained results indicate that the BE3 fraction from Boletus edulis has great potential and needs to be further exploited through animal and clinical studies in order to develop a new efficient and safe therapeutic strategy for people who have been threatened by or suffered from colon cancer.

Galactosylated magnetic nanovectors for regulation of lipid metabolism based on biomarker-specific RNAi and MR imaging.

PubMed

Heo, Dan; Lee, Chanjoo; Ku, Minhee; Haam, Seungjoo; Suh, Jin-Suck; Huh, Yong-Min; Park, Sahng Wook; Yang, Jaemoon

2015-08-21

The specific delivery of ribonucleic acid (RNA) interfering molecules to disease-related cells is still a critical blockade for in vivo systemic treatment. Here, this study suggests a robust delivery carrier for targeted delivery of RNA-interfering molecules using galactosylated magnetic nanovectors (gMNVs). gMNVs are an organic-inorganic polymeric nanomaterial composed of polycationics and magnetic nanocrystal for delivery of RNA-interfering molecules and tracking via magnetic resonance (MR) imaging. In particular, the surface of gMNVs was modified by galactosylgluconic groups for targeted delivering to asialoglycoprotein receptor (ASGPR) of hepatocytes. Moreover, the small interfering RNAs were used to regulate target proteins related with low-density lipoprotein level and in vivo MR imaging was conducted for tracking of nanovectors. The obtained results show that the prepared gMNVs demonstrate potential as a systemic theragnostic nanoplatform for RNA interference and MR imaging.

[Acatalasemia and type 2 diabetes mellitus].

PubMed

Góth, László; Nagy, Teréz; Káplár, Miklós

2015-03-08

The catalase enzyme decomposes the toxic concentrations of hydrogen peroxide into oxygen and water. Hydrogen peroxide is a highly reactive small molecule and its excessive concentration may cause significant damages to proteins, deoxyribonucleic acid, ribonucleic acid and lipids. Acatalasemia refers to inherited deficiency of the catalase enzyme. In this review the authors discuss the possible role of the human catalase enzyme, the metabolism of hydrogen peroxide, and the phenomenon of hydrogen peroxide paradox. In addition, they review data obtained from Hungarian acatalasemic patients indicating an increased frequency of type 2 diabetes mellitus, especially in female patients, and an early onset of type 2 diabetes in these patients. There are 10 catalase gene variants which appear to be responsible for decreased blood catalase activity in acatalasemic patients with type 2 diabetes. It is assumed that low levels of blood catalase may cause an increased concentration of hydrogen peroxide which may contribute to the pathogenesis of type 2 diabetes mellitus.

EPA Registers Innovative Tool to Control Corn Rootworm

EPA Pesticide Factsheets

Ribonucleic acid interference (RNAi) based Plant Incorporated Protectant (PIP) technology is a new and innovative scientific tool utilized by U.S. growers. Learn more about RNAi technology and the 4 new products containing the RNAi based PIP called SMARTST

Problems in aerial application. I, Some biochemical effects of lindane and dieldrin on vertebrates.

DOT National Transportation Integrated Search

1962-05-01

Chronic exposure to the chlorinated hydrocarbon, lindane, elicited alterations in several biochemical values of rat tissues. These included ribonucleic acid quantities, water content, and the cytochrome oxidase activity of heart sarcosomes. The chlor...

The presence, role and clinical use of spermatozoal RNAs

PubMed Central

Jodar, Meritxell; Selvaraju, Sellappan; Sendler, Edward; Diamond, Michael P.; Krawetz, Stephen A.

2013-01-01

BACKGROUND Spermatozoa are highly differentiated, transcriptionally inert cells characterized by a compact nucleus with minimal cytoplasm. Nevertheless they contain a suite of unique RNAs that are delivered to oocyte upon fertilization. They are likely integrated as part of many different processes including genome recognition, consolidation-confrontation, early embryonic development and epigenetic transgenerational inherence. Spermatozoal RNAs also provide a window into the developmental history of each sperm thereby providing biomarkers of fertility and pregnancy outcome which are being intensely studied. METHODS Literature searches were performed to review the majority of spermatozoal RNA studies that described potential functions and clinical applications with emphasis on Next-Generation Sequencing. Human, mouse, bovine and stallion were compared as their distribution and composition of spermatozoal RNAs, using these techniques, have been described. RESULTS Comparisons highlighted the complexity of the population of spermatozoal RNAs that comprises rRNA, mRNA and both large and small non-coding RNAs. RNA-seq analysis has revealed that only a fraction of the larger RNAs retain their structure. While rRNAs are the most abundant and are highly fragmented, ensuring a translationally quiescent state, other RNAs including some mRNAs retain their functional potential, thereby increasing the opportunity for regulatory interactions. Abundant small non-coding RNAs retained in spermatozoa include miRNAs and piRNAs. Some, like miR-34c are essential to the early embryo development required for the first cellular division. Others like the piRNAs are likely part of the genomic dance of confrontation and consolidation. Other non-coding spermatozoal RNAs include transposable elements, annotated lnc-RNAs, intronic retained elements, exonic elements, chromatin-associated RNAs, small-nuclear ILF3/NF30 associated RNAs, quiescent RNAs, mse-tRNAs and YRNAs. Some non-coding RNAs are known to act as epigenetic modifiers, inducing histone modifications and DNA methylation, perhaps playing a role in transgenerational epigenetic inherence. Transcript profiling holds considerable potential for the discovery of fertility biomarkers for both agriculture and human medicine. Comparing the differential RNA profiles of infertile and fertile individuals as well as assessing species similarities, should resolve the regulatory pathways contributing to male factor infertility. CONCLUSIONS Dad delivers a complex population of RNAs to the oocyte at fertilization that likely influences fertilization, embryo development, the phenotype of the offspring and possibly future generations. Development is continuing on the use of spermatozoal RNA profiles as phenotypic markers of male factor status for use as clinical diagnostics of the father's contribution to the birth of a healthy child. PMID:23856356

Small Molecule Chemical Probes of MicroRNA Function

PubMed Central

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R.; Disney, Matthew D.

2015-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as strides are made to understand small molecule recognition of RNA from a fundamental perspective. PMID:25500006

What's Gender Got to Do With It: Difference in the Proportion of Traditionally Female Cases Performed by General Urologists of Each Gender.

PubMed

Rotker, Katherine; Iosifescu, Sarah; Baird, Grayson; Thavaseelan, Simone; Hwang, Kathleen

2018-06-01

To examine surgical case volume characteristics in certifying urologists to evaluate practice patterns, given the long-standing understanding but unproven hypothesis that non-fellowship trained female general urologists perform more urogynecologic procedures compared with their equally trained male counterparts. Case log data from certifying and recertifying urologists from 2000 to 2015 were obtained from the American Board of Urology. Thirty-seven Current Procedural Terminology (CPT) codes were chosen to represent traditionally urogynecologic cases. Logistic regression analysis models were used to determine the percentage of total CPT codes logged during the certification period made up by traditionally urogynecologic cases. Male and female non-fellowship trained, self-described general urologists were compared. The case logs of 4032 non-fellowship trained general urologists were reviewed from 2000 to 2015, 297 of whom were female and 3735 of whom were male. Urogynecologic cases made up 1.27% of the total CPT codes logged by the women and 0.59% of those codes logged by the men (P <.001), an increase of 2.2 times (P <.001). This statistically significant difference persisted regardless of certification period, geographic location, population density, or full-time vs part-time employment. Traditional urogynecologic cases represented a significantly greater percentage of the total cases logged by non-fellowship trained female general urologists compared with their non-fellowship trained, generalist male colleagues. The percentage of total cases performed by both is very small. However, it supports a belief that patient populations differ for male and female general urologists, which may impact training or career choices. Copyright © 2018 Elsevier Inc. All rights reserved.

The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.

PubMed

Shi, Lihua; Zhang, Zhe; Yu, Angela M; Wang, Wei; Wei, Zhi; Akhter, Ehtisham; Maurer, Kelly; Costa Reis, Patrícia; Song, Li; Petri, Michelle; Sullivan, Kathleen E

2014-01-01

Gene expression studies of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) have demonstrated a type I interferon signature and increased expression of inflammatory cytokine genes. Studies of patients with Aicardi Goutières syndrome, commonly cited as a single gene model for SLE, have suggested that accumulation of non-coding RNAs may drive some of the pathologic gene expression, however, no RNA sequencing studies of SLE patients have been performed. This study was designed to define altered expression of coding and non-coding RNAs and to detect globally altered RNA processing in SLE. Purified monocytes from eight healthy age/gender matched controls and nine SLE patients (with low-moderate disease activity and lack of biologic drug use or immune suppressive treatment) were studied using RNA-seq. Quantitative RT-PCR was used to validate findings. Serum levels of endotoxin were measured by ELISA. We found that SLE patients had diminished expression of most endogenous retroviruses and small nucleolar RNAs, but exhibited increased expression of pri-miRNAs. Splicing patterns and polyadenylation were significantly altered. In addition, SLE monocytes expressed novel transcripts, an effect that was replicated by LPS treatment of control monocytes. We further identified increased circulating endotoxin in SLE patients. Monocytes from SLE patients exhibit globally dysregulated gene expression. The transcriptome is not simply altered by the transcriptional activation of a set of genes, but is qualitatively different in SLE. The identification of novel loci, inducible by LPS, suggests that chronic microbial translocation could contribute to the immunologic dysregulation in SLE, a new potential disease mechanism.

The small stellated dodecahedron code and friends.

PubMed

Conrad, J; Chamberland, C; Breuckmann, N P; Terhal, B M

2018-07-13

We explore a distance-3 homological CSS quantum code, namely the small stellated dodecahedron code, for dense storage of quantum information and we compare its performance with the distance-3 surface code. The data and ancilla qubits of the small stellated dodecahedron code can be located on the edges respectively vertices of a small stellated dodecahedron, making this code suitable for three-dimensional connectivity. This code encodes eight logical qubits into 30 physical qubits (plus 22 ancilla qubits for parity check measurements) in contrast with one logical qubit into nine physical qubits (plus eight ancilla qubits) for the surface code. We develop fault-tolerant parity check circuits and a decoder for this code, allowing us to numerically assess the circuit-based pseudo-threshold.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Authors.

Role of Alternative Polyadenylation during Adipogenic Differentiation: An In Silico Approach

PubMed Central

Spangenberg, Lucía; Correa, Alejandro; Dallagiovanna, Bruno; Naya, Hugo

2013-01-01

Post-transcriptional regulation of stem cell differentiation is far from being completely understood. Changes in protein levels are not fully correlated with corresponding changes in mRNAs; the observed differences might be partially explained by post-transcriptional regulation mechanisms, such as alternative polyadenylation. This would involve changes in protein binding, transcript usage, miRNAs and other non-coding RNAs. In the present work we analyzed the distribution of alternative transcripts during adipogenic differentiation and the potential role of miRNAs in post-transcriptional regulation. Our in silico analysis suggests a modest, consistent, bias in 3′UTR lengths during differentiation enabling a fine-tuned transcript regulation via small non-coding RNAs. Including these effects in the analyses partially accounts for the observed discrepancies in relative abundance of protein and mRNA. PMID:24143171

The Non-Coding RNA Ontology (NCRO): a comprehensive resource for the unification of non-coding RNA biology.

PubMed

Huang, Jingshan; Eilbeck, Karen; Smith, Barry; Blake, Judith A; Dou, Dejing; Huang, Weili; Natale, Darren A; Ruttenberg, Alan; Huan, Jun; Zimmermann, Michael T; Jiang, Guoqian; Lin, Yu; Wu, Bin; Strachan, Harrison J; He, Yongqun; Zhang, Shaojie; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming

2016-01-01

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/ncro.owl.

Downregulation of long non-coding RNA LET predicts poor prognosis and increases Notch signaling in non-small cell lung cancer

PubMed Central

Li, Shengwen; Zhao, Hui; Li, Jianqiang; Zhang, Aizheng; Wang, Haibin

2018-01-01

Long non-coding RNAs (lncRNAs) have been found to be dysregulated in a variety of tumors. The lncRNA-Low Expression in Tumor (LET) is a recently identified lncRNA, but its expression pattern and biological significance in human non-small cell lung cancer (NSCLC) are still largely unknown. In this study, we found that lncRNA-LET was significantly downregulated in human NSCLC lung tissues and cell lines. Decreased lncRNA-LET expression was strongly associated with advanced tumor stages and poorer overall survival of NSCLC patients. Functionally, overexpression of lncRNA-LET in NSCLC H292 cells significantly suppressed cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis, while knockdown of lncRNA-LET in NSCLC H1975 cells showed an opposite effect, pointing to a tumor-suppressive role for lncRNA-LET in NSCLC. Mechanistically, we demonstrated that lncRNA-LET overexpression significantly reduced the expression of Notch1 intracellular Domain (NICD1) in H292 cells while knockdown of lncRNA-LET increased NICD1 expression in H1975 cells. Similarly, NSCLC lung tissues with high levels of lncRNA-LET had lower NICD1 expression. Thus, our results provide a strong rationale for lncRNA-LET to be used as a prognostic indicator and a potent therapeutic target for NSCLC patients, and highlight a novel lncRNA-LET/Notch axis in regulating NSCLC cell fate and tumor progression. PMID:29416684

Viroid Pathogenicity: One Process, Many Faces

PubMed Central

Owens, Robert A.; Hammond, Rosemarie W.

2009-01-01

Despite the non-coding nature of their small RNA genomes, the visible symptoms of viroid infection resemble those associated with many plant virus diseases. Recent evidence indicates that viroid-derived small RNAs acting through host RNA silencing pathways play a key role in viroid pathogenicity. Host responses to viroid infection are complex, involving signaling cascades containing host-encoded protein kinases and crosstalk between hormonal and defense-signaling pathways. Studies of viroid-host interaction in the context of entire biochemical or developmental pathways are just beginning, and many working hypotheses have yet to be critically tested. PMID:21994551

Non coding RNAs in vascular disease - from basic science to clinical applications: Scientific update from the Working Group of Myocardial Function of the European Society of Cardiology

PubMed

Fiedler, Jan; Baker, Andrew H; Dimmeler, Stefanie; Heymans, Stephane; Mayr, Manuel; Thum, Thomas

2018-05-23

Non-coding RNAs are increasingly recognized not only as regulators of various biological functions but also as targets for a new generation of RNA therapeutics and biomarkers. We hereby review recent insights relating to non-coding RNAs including microRNAs (e.g. miR-126, miR-146a), long non-coding RNAs (e.g. MIR503HG, GATA6-AS, SMILR) and circular RNAs (e.g. cZNF292) and their role in vascular diseases. This includes identification and therapeutic use of hypoxia-regulated non-coding RNAs and endogenous non-coding RNAs that regulate intrinsic smooth muscle cell signalling, age-related non-coding RNAs and non-coding RNAs involved in the regulation of mitochondrial biology and metabolic control. Finally, we discuss non-coding RNA species with biomarker potential.

Biological significance of long non-coding RNA FTX expression in human colorectal cancer.

PubMed

Guo, Xiao-Bo; Hua, Zhu; Li, Chen; Peng, Li-Pan; Wang, Jing-Shen; Wang, Bo; Zhi, Qiao-Ming

2015-01-01

The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer.

COMMISSION ON EPIDEMIOLOGICAL SURVEY

DTIC Science & Technology

Ribonucleic Acid Metabolism during Infection; Mechanisms of Endotoxin Tolerance; Typhoid Fever: Pathogenesis and Prevention; Studies on Rocky Mountain Spotted Fever : Serologic...Response in Man to Vaccination with Combined Epidemic Typhus, Rocky Mountain Spotted Fever and Q Fever Vaccine; and Influence of Tularemia on Insulin Secretion.

Endogenous small RNAs and antibacterial immunity in plants.

PubMed

Jin, Hailing

2008-08-06

Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Virus-derived small RNAs induce silencing of viral RNAs and are essential for antiviral defense in both animal and plant systems. The role of host endogenous small RNAs on antibacterial immunity has only recently been recognized. Host disease resistance and defense responses are achieved by activation and repression of a large array of genes. Certain endogenous small RNAs in plants, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are induced or repressed in response to pathogen attack and subsequently regulate the expression of genes involved in disease resistance and defense responses by mediating transcriptional or post-transcriptional gene silencing. Thus, these small RNAs play an important role in gene expression reprogramming in plant disease resistance and defense responses. This review focuses on the recent findings of plant endogenous small RNAs in antibacterial immunity.

Attacks on quantum key distribution protocols that employ non-ITS authentication

NASA Astrophysics Data System (ADS)

Pacher, C.; Abidin, A.; Lorünser, T.; Peev, M.; Ursin, R.; Zeilinger, A.; Larsson, J.-Å.

2016-01-01

We demonstrate how adversaries with large computing resources can break quantum key distribution (QKD) protocols which employ a particular message authentication code suggested previously. This authentication code, featuring low key consumption, is not information-theoretically secure (ITS) since for each message the eavesdropper has intercepted she is able to send a different message from a set of messages that she can calculate by finding collisions of a cryptographic hash function. However, when this authentication code was introduced, it was shown to prevent straightforward man-in-the-middle (MITM) attacks against QKD protocols. In this paper, we prove that the set of messages that collide with any given message under this authentication code contains with high probability a message that has small Hamming distance to any other given message. Based on this fact, we present extended MITM attacks against different versions of BB84 QKD protocols using the addressed authentication code; for three protocols, we describe every single action taken by the adversary. For all protocols, the adversary can obtain complete knowledge of the key, and for most protocols her success probability in doing so approaches unity. Since the attacks work against all authentication methods which allow to calculate colliding messages, the underlying building blocks of the presented attacks expose the potential pitfalls arising as a consequence of non-ITS authentication in QKD post-processing. We propose countermeasures, increasing the eavesdroppers demand for computational power, and also prove necessary and sufficient conditions for upgrading the discussed authentication code to the ITS level.

Diversity-optimal power loading for intensity modulated MIMO optical wireless communications.

PubMed

Zhang, Yan-Yu; Yu, Hong-Yi; Zhang, Jian-Kang; Zhu, Yi-Jun

2016-04-18

In this paper, we consider the design of space code for an intensity modulated direct detection multi-input-multi-output optical wireless communication (IM/DD MIMO-OWC) system, in which channel coefficients are independent and non-identically log-normal distributed, with variances and means known at the transmitter and channel state information available at the receiver. Utilizing the existing space code design criterion for IM/DD MIMO-OWC with a maximum likelihood (ML) detector, we design a diversity-optimal space code (DOSC) that maximizes both large-scale diversity and small-scale diversity gains and prove that the spatial repetition code (RC) with a diversity-optimized power allocation is diversity-optimal among all the high dimensional nonnegative space code schemes under a commonly used optical power constraint. In addition, we show that one of significant advantages of the DOSC is to allow low-complexity ML detection. Simulation results indicate that in high signal-to-noise ratio (SNR) regimes, our proposed DOSC significantly outperforms RC, which is the best space code currently available for such system.

Potential miRNA regulators of differential HPG axis gene expression between low egg producing and high egg producing turkey hens

USDA-ARS?s Scientific Manuscript database

Expression differences exist in key genes of the hypothalamo-pituitary-gonadal (HPG) axis in low egg producing hens (LEPH) and high egg producing hens (HEPH); however, regulation of these differences is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that play a role in post-transcriptional re...

Genome-wide piRNA profiles of virus transmitting whitefly Bemisia tabaci during feeding on TYLCV-infected tomato

USDA-ARS?s Scientific Manuscript database

Small RNAs (sRNAs) are 20-31 nucleotide (nt) non-coding regulatory elements commonly found in plants and animals, which are classified as short interfering RNA (siRNA), microRNA (miRNA) and Piwi-interacting RNA (piRNA). The whitefly Bemisia tabaci MEAM1 is a vector capable of transmitting many devas...

Small RNA profiling of Dengue virus-mosquito interactions implicates the PIWI RNA pathway in anti-viral defense

PubMed Central

2011-01-01

Background Small RNA (sRNA) regulatory pathways (SRRPs) are important to anti-viral defence in mosquitoes. To identify critical features of the virus infection process in Dengue serotype 2 (DENV2)-infected Ae. aegypti, we deep-sequenced small non-coding RNAs. Triplicate biological replicates were used so that rigorous statistical metrics could be applied. Results In addition to virus-derived siRNAs (20-23 nts) previously reported for other arbovirus-infected mosquitoes, we show that PIWI pathway sRNAs (piRNAs) (24-30 nts) and unusually small RNAs (usRNAs) (13-19 nts) are produced in DENV-infected mosquitoes. We demonstrate that a major catalytic enzyme of the siRNA pathway, Argonaute 2 (Ago2), co-migrates with a ~1 megadalton complex in adults prior to bloodfeeding. sRNAs were cloned and sequenced from Ago2 immunoprecipitations. Viral sRNA patterns change over the course of infection. Host sRNAs were mapped to the published aedine transcriptome and subjected to analysis using edgeR (Bioconductor). We found that sRNA profiles are altered early in DENV2 infection, and mRNA targets from mitochondrial, transcription/translation, and transport functional categories are affected. Moreover, small non-coding RNAs (ncRNAs), such as tRNAs, spliceosomal U RNAs, and snoRNAs are highly enriched in DENV-infected samples at 2 and 4 dpi. Conclusions These data implicate the PIWI pathway in anti-viral defense. Changes to host sRNA profiles indicate that specific cellular processes are affected during DENV infection, such as mitochondrial function and ncRNA levels. Together, these data provide important progress in understanding the DENV2 infection process in Ae. aegypti. PMID:21356105

Discrimination of Spore-Forming Bacilli Using spoIVA

NASA Technical Reports Server (NTRS)

Venkateswaran, Kasthuri; LaDuc, Myron; Stuecker, Tara

2009-01-01

A method of discriminating between spore-forming and non-spore-forming bacteria is based on a combination of simultaneous sporulation-specific and non-sporulation-specific quantitative polymerase chain reactions (Q-PCRs). The method was invented partly in response to the observation that for the purposes of preventing or reducing biological contamination affecting many human endeavors, ultimately, only the spore-forming portions of bacterial populations are the ones that are problematic (or, at least, more problematic than are the non-spore-forming portions). In some environments, spore-forming bacteria constitute small fractions of the total bacterial populations. The use of sporulation-specific primers in Q-PCR affords the ability to assess the spore-forming fraction of a bacterial population present in an environment of interest. This assessment can provide a more thorough and accurate understanding of the bacterial contamination in the environment, thereby making it possible to focus contamination- testing, contamination-prevention, sterilization, and decontamination resources more economically and efficiently. The method includes the use of sporulation-specific primers in the form of designed, optimized deoxyribonucleic acid (DNA) oligonucleotides specific for the bacterial spoIVA gene (see table). [In "spoIVA," "IV" signifies Roman numeral four and the entire quoted name refers to gene A for the fourth stage of sporulation.] These primers are mixed into a PCR cocktail with a given sample of bacterial cells. A control PCR cocktail into which are mixed universal 16S rRNA primers is also prepared. ["16S rRNA" denotes a ribosomal ribonucleic acid (rRNA) sequence that is common to all organisms.] Following several cycles of heating and cooling according to the PCR protocol to amplify amounts of DNA molecules, the amplification products can be analyzed to determine the types of bacterial cells present within the samples. If the amplification product is strong, relative to the product of a control PCR sequence, then it is concluded that the bacterial population in the sample consists predominantly of spore-forming cells. If the amplification product is weak or nonexistent, then it is concluded that the bacterial population in the sample consists predominantly or entirely of non-spore-forming cells.

Transposon-driven transcription is a conserved feature of vertebrate spermatogenesis and transcript evolution.

PubMed

Davis, Matthew P; Carrieri, Claudia; Saini, Harpreet K; van Dongen, Stijn; Leonardi, Tommaso; Bussotti, Giovanni; Monahan, Jack M; Auchynnikava, Tania; Bitetti, Angelo; Rappsilber, Juri; Allshire, Robin C; Shkumatava, Alena; O'Carroll, Dónal; Enright, Anton J

2017-07-01

Spermatogenesis is associated with major and unique changes to chromosomes and chromatin. Here, we sought to understand the impact of these changes on spermatogenic transcriptomes. We show that long terminal repeats (LTRs) of specific mouse endogenous retroviruses (ERVs) drive the expression of many long non-coding transcripts (lncRNA). This process occurs post-mitotically predominantly in spermatocytes and round spermatids. We demonstrate that this transposon-driven lncRNA expression is a conserved feature of vertebrate spermatogenesis. We propose that transposon promoters are a mechanism by which the genome can explore novel transcriptional substrates, increasing evolutionary plasticity and allowing for the genesis of novel coding and non-coding genes. Accordingly, we show that a small fraction of these novel ERV-driven transcripts encode short open reading frames that produce detectable peptides. Finally, we find that distinct ERV elements from the same subfamilies act as differentially activated promoters in a tissue-specific context. In summary, we demonstrate that LTRs can act as tissue-specific promoters and contribute to post-mitotic spermatogenic transcriptome diversity. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Decoding the ubiquitous role of microRNAs in neurogenesis.

PubMed

Nampoothiri, Sreekala S; Rajanikant, G K

2017-04-01

Neurogenesis generates fledgling neurons that mature to form an intricate neuronal circuitry. The delusion on adult neurogenesis was far resolved in the past decade and became one of the largely explored domains to identify multifaceted mechanisms bridging neurodevelopment and neuropathology. Neurogenesis encompasses multiple processes including neural stem cell proliferation, neuronal differentiation, and cell fate determination. Each neurogenic process is specifically governed by manifold signaling pathways, several growth factors, coding, and non-coding RNAs. A class of small non-coding RNAs, microRNAs (miRNAs), is ubiquitously expressed in the brain and has emerged to be potent regulators of neurogenesis. It functions by fine-tuning the expression of specific neurogenic gene targets at the post-transcriptional level and modulates the development of mature neurons from neural progenitor cells. Besides the commonly discussed intrinsic factors, the neuronal morphogenesis is also under the control of several extrinsic temporal cues, which in turn are regulated by miRNAs. This review enlightens on dicer controlled switch from neurogenesis to gliogenesis, miRNA regulation of neuronal maturation and the differential expression of miRNAs in response to various extrinsic cues affecting neurogenesis.

Biological significance of long non-coding RNA FTX expression in human colorectal cancer

PubMed Central

Guo, Xiao-Bo; Hua, Zhu; Li, Chen; Peng, Li-Pan; Wang, Jing-Shen; Wang, Bo; Zhi, Qiao-Ming

2015-01-01

The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer. PMID:26629053

Reducing acetate excretion from E. coli K-12 by over-expressing the small RNA sgrS

PubMed Central

Negrete, Alejandro; Majdalani, Nadim; Phue, Je Nie; Shiloach, Joseph

2011-01-01

When exposed to the non-metabolized glucose derivative alpha methyl glucoside, both E. coli K-12 (JM109 and MG1655) and E. coli B (BL21) respond by reducing the concentration of the mRNA of the ptsG gene which is responsible for the biosynthesis of the glucose transporter EIICBglu. This occurs through the over-expression of the non-coding small RNA SgrS, which interacts specifically with the mRNA of the ptsG gene and prevents its translation. However, when these bacteria are exposed to a glucose concentration of 40 g/L, over-expression of SgrS is observed only in E. coli B (BL21). Unlike E. coli K-12 (JM109 and MG1655), which are affected by high glucose concentration and produce higher levels of acetate, E. coli B (BL21) is not affected. Based on this information, it was assumed that over-expression of SgrS enables E. coli B (BL21) to reduce its acetate excretion by controlling the glucose transport. When SgrS was over-expressed in both E. coli K-12 strains from a multicopy plasmid, it was possible to reduce their acetate excretion levels to those seen in E. coli B. This observation opens a new approach towards controlling bacterial metabolism through the use of non-coding RNA. PMID:22107968

COMMISSION ON EPIDEMIOLOGICAL SURVEY

DTIC Science & Technology

Ribonucleic Acid Metabolism during Infection; Mechanisms of Endotoxin Tolerance; Typhoid Fever: Pathogenesis and Prevention; Studies on Rocky Mountain Spotted Fever : Serologic...Response in Man to Vaccination with Combined Epidemic Typhus, Rocky Mountain Spotted Fever and Q Fever Vaccine; and Influence of Tularemia on Tularemia on Insulin Secretion.

RNA.

ERIC Educational Resources Information Center

Darnell, James E., Jr.

1985-01-01

Ribonucleic acid (RNA) converts genetic information into protein and usually must be processed to serve its function. RNA types, chemical structure, protein synthesis, translation, manufacture, and processing are discussed. Concludes that the first genes might have been spliced RNA and that humans might be closer than bacteria to primitive…

The diversity of the orthoreoviruses: molecular taxonomy and phylogentic divides.

USDA-ARS?s Scientific Manuscript database

The family Reoviridae is a diverse group of viruses with double-stranded ribonucleic acid (RNA) genomes contained within icosahedral, layered protein capsids. Within the Reoviridae, the Orthoreovirus genus includes viruses that infect reptiles, birds and mammals (including humans). Recent sequencing...

Small molecule chemical probes of microRNA function.

PubMed

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R; Disney, Matthew D

2015-02-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as progress is made in understanding small molecule recognition of RNA. Copyright © 2014. Published by Elsevier Ltd.

AMPK regulates energy metabolism through the SIRT1 signaling pathway to improve myocardial hypertrophy.

PubMed

Dong, H-W; Zhang, L-F; Bao, S-L

2018-05-01

We investigated the correlations of adenosine monophosphate-activated protein kinase (AMPK), Silence information regulator 1 (SIRT1) and energy metabolism with myocardial hypertrophy. Myocardial hypertrophy experimental model was established via transverse aortic constriction (TAC)-induced myocardial hypertrophy and phenylephrine (PE)-induced hypertrophic myocardial cell culture. After activation of AMPK, the messenger ribonucleic acid (mRNA) expressions in myocardial tissue- and myocardial cell hypertrophy-related genes, atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC), were detected. The production rate of 14C-labeled 14CO2 from palmitic acid was quantitatively determined to detect the fatty acid and glucose oxidation of hypertrophic myocardial tissues or cells, and the glucose uptake of myocardial cells was studied using [14C] glucose. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to detect the changes in SIRT1 mRNA and protein expressions in hypertrophic myocardial tissues. Moreover, SIRT1 small interfering ribonucleic acid (siRNA) was used to interfere in SIRT1 expression to further investigate the role of SIRT1 in the effect of AMPK activation on myocardial hypertrophy. AMPK activation could significantly reduce the mRNA expressions of ANP and β-MHC in vitro and in vivo. AMPK could increase the ejection fraction (EF) and decrease the protein synthesis rate in myocardial cells in mice with myocardial hypertrophy. Besides, AMPK activation could increase the fatty acid oxidation, improve the glucose uptake and reduce the glucose oxidation. After AMPK activation, both SIRT1 mRNA and protein expressions in hypertrophic myocardial tissues and myocardial cells were increased. After SIRT1 siRNA was further used to interfere in SIRT1 expression in myocardial cells, it was found that mRNA expressions and protein synthesis rates of ANP and β-MHC were increased. The activation of AMPK can inhibit the myocardial hypertrophy, which may be realized through regulating the myocardial energy metabolism via SIRT1 signaling pathway.

Epstein-Barr virus associated T-cell lymphoproliferative disease misdiagnosed as ulcerative colitis: a case report.

PubMed

Zheng, Xiaodan; Xie, Jianlan; Zhou, Xiaoge

2015-01-01

Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disease (LPD) is not uncommon in China, but gastrointestinal involvement is very rare. We report on an immunocompetent patient with EBV-associated T-cell LPD of the colon. The 26-year-old man was initially misdiagnosed with ulcerative colitis (UC). A colon biopsy revealed the presence of small to medium-sized lymphoid cells infiltrating the intestinal wall. The neoplastic cells expressed CD3, CD5, and granzyme B, not CD56. EBV-encoded small ribonucleic acid was detected in the tumor cells of the colon as well as the lymph node, and the T-cell receptor gene rearrangement result displayed δ gene monoclonal rearrangement. The patient died 2 moths after the diagnosis. The clinical course of EBV-associated T-cell LPD is aggressive and the prognosis is poor, the wrong diagnosis may delay treatment. Therefore, we should be very careful to prevent misdiagnosis. When patients have multiple intestinal ulcers that are not typical of UC and the clinical course is unusual, although morphology looks like inflammatory change, pathologist should consider the possibility of EBV-associated LPD. The treatment strategy and prognosis of these two diseases are different.

Web-accessible molecular modeling with Rosetta: The Rosetta Online Server that Includes Everyone (ROSIE).

PubMed

Moretti, Rocco; Lyskov, Sergey; Das, Rhiju; Meiler, Jens; Gray, Jeffrey J

2018-01-01

The Rosetta molecular modeling software package provides a large number of experimentally validated tools for modeling and designing proteins, nucleic acids, and other biopolymers, with new protocols being added continually. While freely available to academic users, external usage is limited by the need for expertise in the Unix command line environment. To make Rosetta protocols available to a wider audience, we previously created a web server called Rosetta Online Server that Includes Everyone (ROSIE), which provides a common environment for hosting web-accessible Rosetta protocols. Here we describe a simplification of the ROSIE protocol specification format, one that permits easier implementation of Rosetta protocols. Whereas the previous format required creating multiple separate files in different locations, the new format allows specification of the protocol in a single file. This new, simplified protocol specification has more than doubled the number of Rosetta protocols available under ROSIE. These new applications include pK a determination, lipid accessibility calculation, ribonucleic acid redesign, protein-protein docking, protein-small molecule docking, symmetric docking, antibody docking, cyclic toxin docking, critical binding peptide determination, and mapping small molecule binding sites. ROSIE is freely available to academic users at http://rosie.rosettacommons.org. © 2017 The Protein Society.

Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury.

PubMed

Kölling, Malte; Genschel, Celina; Kaucsar, Tamas; Hübner, Anika; Rong, Song; Schmitt, Roland; Sörensen-Zender, Inga; Haddad, George; Kistler, Andreas; Seeger, Harald; Kielstein, Jan T; Fliser, Danilo; Haller, Hermann; Wüthrich, Rudolf; Zörnig, Martin; Thum, Thomas; Lorenzen, Johan

2018-02-21

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was transcriptionally activated by hypoxia-inducible factor 1-α. In vitro, Malat1 inhibition reduced proliferation and the number of endothelial cells in the S-phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed similar degrees of outer medullary tubular epithelial injury, proliferation, capillary rarefaction, inflammation and fibrosis, survival and kidney function. Small-RNA sequencing and whole genome expression analysis revealed only minor changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous studies, which suggested a prominent role of Malat1 in the induction of disease, we did not confirm an in vivo role of Malat1 concerning renal I/R-injury.

Present Scenario of Long Non-Coding RNAs in Plants

PubMed Central

Bhatia, Garima; Goyal, Neetu; Sharma, Shailesh; Upadhyay, Santosh Kumar; Singh, Kashmir

2017-01-01

Small non-coding RNAs have been extensively studied in plants over the last decade. In contrast, genome-wide identification of plant long non-coding RNAs (lncRNAs) has recently gained momentum. LncRNAs are now being recognized as important players in gene regulation, and their potent regulatory roles are being studied comprehensively in eukaryotes. LncRNAs were first reported in humans in 1992. Since then, research in animals, particularly in humans, has rapidly progressed, and a vast amount of data has been generated, collected, and organized using computational approaches. Additionally, numerous studies have been conducted to understand the roles of these long RNA species in several diseases. However, the status of lncRNA investigation in plants lags behind that in animals (especially humans). Efforts are being made in this direction using computational tools and high-throughput sequencing technologies, such as the lncRNA microarray technique, RNA-sequencing (RNA-seq), RNA capture sequencing, (RNA CaptureSeq), etc. Given the current scenario, significant amounts of data have been produced regarding plant lncRNAs, and this amount is likely to increase in the subsequent years. In this review we have documented brief information about lncRNAs and their status of research in plants, along with the plant-specific resources/databases for information retrieval on lncRNAs. PMID:29657289

Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.

PubMed Central

Jacobson, L A; Jen-Jacobson, L

1980-01-01

We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down. PMID:6155375

Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.

PubMed

Jacobson, L A; Jen-Jacobson, L

1980-06-01

We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down.

Ribonucleic Acid and Ribosomes of Bacillus stearothermophilus1

PubMed Central

Saunders, Grady F.; Campbell, L. Leon

1966-01-01

Saunders, Grady F. (University of Illinois, Urbana), and L. Leon Campbell. Ribonucleic acid and ribosomes of Bacillus stearothermophilus. J. Bacteriol. 91:332–339. 1966.—The ability of some thermophilic bacteria to grow at temperatures as high as 76 C emphasizes the remarkable thermal stability of their crucial macromolecules. An investigation of the ribonucleic acid (RNA) and ribosomes of Bacillus stearothermophilus was conducted. Washed log-phase cells were disrupted either by sonic treatment or by alumina grinding in 10−2m MgCl2–10−2m tris-(hydroxymethyl)aminomethane buffer, pH 7.4 (TM buffer). Ultracentrifugal analysis revealed peaks at 72.5S, 101S, and 135S, with the 101S peak being the most prominent. By lowering the Mg++ concentration to 10−3m, the ribosome preparation was dissociated to give 40S, 31S, and 54S peaks. These in turn were reassociated in the presence of 10−2m Mg++ to give the larger 73S and 135S particles. When heated in TM buffer, Escherichia coli ribosomes began a gradual dissociation at 58 C, and at 70 C underwent a large hyperchromic shift with a Tm at 72.8 C. In contrast, B. stearothermophilus ribosomes did not show a hyperchromic shift below 70 C; they had a Tm of 77.9 C. The thermal denaturation curves of the 4S, 16S, and 23S RNA from both organisms were virtually identical. The gross amino acid composition of B. stearothermophilus ribosomes showed no marked differences from that reported for E. coli ribosomes. These data suggest that the unusual thermal stability of B. stearothermophilus ribosomes may reflect either an unusual packing arrangement of the protein to the RNA or differences in the primary structure of the ribosomal proteins. Images PMID:5903099

RIP-seq of BmAgo2-associated small RNAs reveal various types of small non-coding RNAs in the silkworm, Bombyx mori

PubMed Central

2013-01-01

Background Small non-coding RNAs (ncRNAs) are important regulators of gene expression in eukaryotes. Previously, only microRNAs (miRNAs) and piRNAs have been identified in the silkworm, Bombyx mori. Furthermore, only ncRNAs (50-500nt) of intermediate size have been systematically identified in the silkworm. Results Here, we performed a systematic identification and analysis of small RNAs (18-50nt) associated with the Bombyx mori argonaute2 (BmAgo2) protein. Using RIP-seq, we identified various types of small ncRNAs associated with BmAGO2. These ncRNAs showed a multimodal length distribution, with three peaks at ~20nt, ~27nt and ~33nt, which included tRNA-, transposable element (TE)-, rRNA-, snoRNA- and snRNA-derived small RNAs as well as miRNAs and piRNAs. The tRNA-derived fragments (tRFs) were found at an extremely high abundance and accounted for 69.90% of the BmAgo2-associated small RNAs. Northern blotting confirmed that many tRFs were expressed or up-regulated only in the BmNPV-infected cells, implying that the tRFs play a prominent role by binding to BmAgo2 during BmNPV infection. Additional evidence suggested that there are potential cleavage sites on the D, anti-codon and TψC loops of the tRNAs. TE-derived small RNAs and piRNAs also accounted for a significant proportion of the BmAgo2-associated small RNAs, suggesting that BmAgo2 could be involved in the maintenance of genome stability by suppressing the activities of transposons guided by these small RNAs. Finally, Northern blotting was also used to confirm the Bombyx 5.8 s rRNA-derived small RNAs, demonstrating that various novel small RNAs exist in the silkworm. Conclusions Using an RIP-seq method in combination with Northern blotting, we identified various types of small RNAs associated with the BmAgo2 protein, including tRNA-, TE-, rRNA-, snoRNA- and snRNA-derived small RNAs as well as miRNAs and piRNAs. Our findings provide new clues for future functional studies of the role of small RNAs in insect development and evolution. PMID:24074203

A Non Local Electron Heat Transport Model for Multi-Dimensional Fluid Codes

NASA Astrophysics Data System (ADS)

Schurtz, Guy

2000-10-01

Apparent inhibition of thermal heat flow is one of the most ancient problems in computational Inertial Fusion and flux-limited Spitzer-Harm conduction has been a mainstay in multi-dimensional hydrodynamic codes for more than 25 years. Theoretical investigation of the problem indicates that heat transport in laser produced plasmas has to be considered as a non local process. Various authors contributed to the non local theory and proposed convolution formulas designed for practical implementation in one-dimensional fluid codes. Though the theory, confirmed by kinetic calculations, actually predicts a reduced heat flux, it fails to explain the very small limiters required in two-dimensional simulations. Fokker-Planck simulations by Epperlein, Rickard and Bell [PRL 61, 2453 (1988)] demonstrated that non local effects could lead to a strong reduction of heat flow in two dimensions, even in situations where a one-dimensional analysis suggests that the heat flow is nearly classical. We developed at CEA/DAM a non local electron heat transport model suitable for implementation in our two-dimensional radiation hydrodynamic code FCI2. This model may be envisionned as the first step of an iterative solution of the Fokker-Planck equations; it takes the mathematical form of multigroup diffusion equations, the solution of which yields both the heat flux and the departure of the electron distribution function to the Maxwellian. Although direct implementation of the model is straightforward, formal solutions of it can be expressed in convolution form, exhibiting a three-dimensional tensor propagator. Reduction to one dimension retrieves the original formula of Luciani, Mora and Virmont [PRL 51, 1664 (1983)]. Intense magnetic fields may be generated by thermal effects in laser targets; these fields, as well as non local effects, will inhibit electron conduction. We present simulations where both effects are taken into account and shortly discuss the coupling strategy between them.

The mitochondrial genomes of the acoelomorph worms Paratomella rubra, Isodiametra pulchra and Archaphanostoma ylvae.

PubMed

Robertson, Helen E; Lapraz, François; Egger, Bernhard; Telford, Maximilian J; Schiffer, Philipp H

2017-05-12

Acoels are small, ubiquitous - but understudied - marine worms with a very simple body plan. Their internal phylogeny is still not fully resolved, and the position of their proposed phylum Xenacoelomorpha remains debated. Here we describe mitochondrial genome sequences from the acoels Paratomella rubra and Isodiametra pulchra, and the complete mitochondrial genome of the acoel Archaphanostoma ylvae. The P. rubra and A. ylvae sequences are typical for metazoans in size and gene content. The larger I. pulchra  mitochondrial genome contains both ribosomal genes, 21 tRNAs, but only 11 protein-coding genes. We find evidence suggesting a duplicated sequence in the I. pulchra mitochondrial genome. The P. rubra, I. pulchra and A. ylvae mitochondria have a unique genome organisation in comparison to other metazoan mitochondrial genomes. We found a large degree of protein-coding gene and tRNA overlap with little non-coding sequence in the compact P. rubra genome. Conversely, the A. ylvae and I. pulchra genomes have many long non-coding sequences between genes, likely driving genome size expansion in the latter. Phylogenetic trees inferred from mitochondrial genes retrieve Xenacoelomorpha as an early branching taxon in the deuterostomes. Sequence divergence analysis between P. rubra sampled in England and Spain indicates cryptic diversity.

New technologies accelerate the exploration of non-coding RNAs in horticultural plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Degao; Mewalal, Ritesh; Hu, Rongbin

Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial regulators of a variety of biological processes in plants. While protein-encoding genes have been relatively well-annotated in sequenced genomes, accounting for a small portion of the genome space in plants, the universe of plant ncRNAs is rapidly expanding. Recent advances in experimental and computational technologies have generated a great momentum for discovery and functional characterization of ncRNAs. Here we summarize the classification and known biological functions of plant ncRNAs, review the application of next-generation sequencing (NGS) technology and ribosome profiling technology to ncRNA discovery in horticultural plants andmore » discuss the application of new technologies, especially the new genome-editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional characterization of plant ncRNAs.« less

MicroRNAs in large herpesvirus DNA genomes: recent advances.

PubMed

Sorel, Océane; Dewals, Benjamin G

2016-08-01

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that regulate gene expression. They alter mRNA translation through base-pair complementarity, leading to regulation of genes during both physiological and pathological processes. Viruses have evolved mechanisms to take advantage of the host cells to multiply and/or persist over the lifetime of the host. Herpesviridae are a large family of double-stranded DNA viruses that are associated with a number of important diseases, including lymphoproliferative diseases. Herpesviruses establish lifelong latent infections through modulation of the interface between the virus and its host. A number of reports have identified miRNAs in a very large number of human and animal herpesviruses suggesting that these short non-coding transcripts could play essential roles in herpesvirus biology. This review will specifically focus on the recent advances on the functions of herpesvirus miRNAs in infection and pathogenesis.

New technologies accelerate the exploration of non-coding RNAs in horticultural plants

PubMed Central

Liu, Degao; Mewalal, Ritesh; Hu, Rongbin; Tuskan, Gerald A; Yang, Xiaohan

2017-01-01

Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial regulators of a variety of biological processes in plants. While protein-encoding genes have been relatively well-annotated in sequenced genomes, accounting for a small portion of the genome space in plants, the universe of plant ncRNAs is rapidly expanding. Recent advances in experimental and computational technologies have generated a great momentum for discovery and functional characterization of ncRNAs. Here we summarize the classification and known biological functions of plant ncRNAs, review the application of next-generation sequencing (NGS) technology and ribosome profiling technology to ncRNA discovery in horticultural plants and discuss the application of new technologies, especially the new genome-editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional characterization of plant ncRNAs. PMID:28698797

Asian citrus psyllid RNAi pathway - RNAi evidence

USDA-ARS?s Scientific Manuscript database

In silico analyses of the draft genome of Diaphorina citri, the Asian citrus psyllid, for genes within the Ribonucleic acid interference(RNAi), pathway was successful. The psyllid is the vector of the plant-infecting bacterium, Candidatus Liberibacter asiaticus (CLas), which is linked to citrus gree...

Discovery of huanglongbing (HLB) pre-symptomatic Ribonucleic acid (RNA) biomarkers

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) is the most devastating citrus disease and is associated with vector-borne Liberibacter. Currently there is no cure for huanglongbing. Visual disease symptoms appear in only a few leaves months after initial Liberibacter exposure compromising disease management by tree removal. S...

GENETIC INDICATORS OF ENVIRONMENTAL STRESS IN HERMATYPIC CORALS

EPA Science Inventory

An efficient, low cost method was developed for the detection of rapid changes in coral gene expression at the messenger ribonucleic acid (mRNA) level. Hermatypic (stony) corals were exposed to a variety of organic and inorganic toxicants and physical stressors at several concent...

Detection of miRNA using a double-strand displacement biosensor with a self-complementary fluorescent reporter.

PubMed

Larkey, Nicholas E; Almlie, C Kyle; Tran, Victoria; Egan, Marianne; Burrows, Sean M

2014-02-04

Design of rapid, selective, and sensitive DNA and ribonucleic acid (RNA) biosensors capable of minimizing false positives from nuclease degradation is crucial for translational research and clinical diagnostics. We present proof-of-principle studies of an innovative micro-ribonucleic acid (miRNA) reporter-probe biosensor that displaces a self-complementary reporter, while target miRNA binds to the probe. The freed reporter folds into a hairpin structure to induce a decrease in the fluorescent signal. The self-complementarity of the reporter facilitates the reduction of false positives from nuclease degradation. Nanomolar limits of detection and quantitation were capable with this proof-of-principle design. Detection of miRNA occurs within 10 min and does not require any additional hybridization, labeling, or rinsing steps. The potential for medical applications of the reporter-probe biosensor is demonstrated by selective detection of a cancer regulating microRNA, Lethal-7 (Let-7a). Mechanisms for transporting the biosensor across the cell membrane will be the focus of future work.

48 CFR 19.303 - Determining North American Industry Classification System codes and size standards.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Industry Classification System codes and size standards. 19.303 Section 19.303 Federal Acquisition... of Small Business Status for Small Business Programs 19.303 Determining North American Industry... North American Industry Classification System (NAICS) code and related small business size standard and...

The NAICS Code Selection Process And Small Business Participation

DTIC Science & Technology

2016-03-01

specialist 15. NUMBER OF PAGES 59 16. PRICE CODE 17. SECURITY CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE...FPDS-NG) website and information gathered from interviews with small business specialists . The data include contract actions from 276 contracts with...used interviews to determine if small businesses are affected by inappropriate NAICS code selection. None of the six small business specialists we

The non-coding RNA landscape of human hematopoiesis and leukemia.

PubMed

Schwarzer, Adrian; Emmrich, Stephan; Schmidt, Franziska; Beck, Dominik; Ng, Michelle; Reimer, Christina; Adams, Felix Ferdinand; Grasedieck, Sarah; Witte, Damian; Käbler, Sebastian; Wong, Jason W H; Shah, Anushi; Huang, Yizhou; Jammal, Razan; Maroz, Aliaksandra; Jongen-Lavrencic, Mojca; Schambach, Axel; Kuchenbauer, Florian; Pimanda, John E; Reinhardt, Dirk; Heckl, Dirk; Klusmann, Jan-Henning

2017-08-09

Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear. Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helfenbein, Kevin G.; Brown, Wesley M.; Boore, Jeffrey L.

We have sequenced the complete mitochondrial DNA (mtDNA) of the articulate brachiopod Terebratalia transversa. The circular genome is 14,291 bp in size, relatively small compared to other published metazoan mtDNAs. The 37 genes commonly found in animal mtDNA are present; the size decrease is due to the truncation of several tRNA, rRNA, and protein genes, to some nucleotide overlaps, and to a paucity of non-coding nucleotides. Although the gene arrangement differs radically from those reported for other metazoans, some gene junctions are shared with two other articulate brachiopods, Laqueus rubellus and Terebratulina retusa. All genes in the T. transversa mtDNA,more » unlike those in most metazoan mtDNAs reported, are encoded by the same strand. The A+T content (59.1 percent) is low for a metazoan mtDNA, and there is a high propensity for homopolymer runs and a strong base-compositional strand bias. The coding strand is quite G+T-rich, a skew that is shared by the confamilial (laqueid) specie s L. rubellus, but opposite to that found in T. retusa, a cancellothyridid. These compositional skews are strongly reflected in the codon usage patterns and the amino acid compositions of the mitochondrial proteins, with markedly different usage observed between T. retusa and the two laqueids. This observation, plus the similarity of the laqueid non-coding regions to the reverse complement of the non-coding region of the cancellothyridid, suggest that an inversion that resulted in a reversal in the direction of first-strand replication has occurred in one of the two lineages. In addition to the presence of one non-coding region in T. transversa that is comparable to those in the other brachiopod mtDNAs, there are two others with the potential to form secondary structures; one or both of these may be involved in the process of transcript cleavage.« less

Periodic response of nonlinear systems

NASA Technical Reports Server (NTRS)

Nataraj, C.; Nelson, H. D.

1988-01-01

A procedure is developed to determine approximate periodic solutions of autonomous and non-autonomous systems. The trignometric collocation method (TCM) is formalized to allow for the analysis of relatively small order systems directly in physical coordinates. The TCM is extended to large order systems by utilizing modal analysis in a component mode synthesis strategy. The procedure was coded and verified by several check cases. Numerical results for two small order mechanical systems and one large order rotor dynamic system are presented. The method allows for the possibility of approximating periodic responses for large order forced and self-excited nonlinear systems.

Analysis of a tungsten sputtering experiment in DIII-D and code/data validation of high redeposition/reduced erosion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wampler, William R.; Brooks, J. N.; Elder, J. D.

2015-03-29

We analyze a DIII-D tokamak experiment where two tungsten spots on the removable DiMES divertor probe were exposed to 12 s of attached plasma conditions, with moderate strike point temperature and density (~20 eV, ~4.5 × 10 19 m –3), and 3% carbon impurity content. Both very small (1 mm diameter) and small (1 cm diameter) deposited samples were used for assessing gross and net tungsten sputtering erosion. The analysis uses a 3-D erosion/redeposition code package (REDEP/WBC), with input from a diagnostic-calibrated near-surface plasma code (OEDGE), and with focus on charge state resolved impinging carbon ion flux and energy. Themore » tungsten surfaces are primarily sputtered by the carbon, in charge states +1 to +4. We predict high redeposition (~75%) of sputtered tungsten on the 1 cm spot—with consequent reduced net erosion—and this agrees well with post-exposure DiMES probe RBS analysis data. As a result, this study and recent related work is encouraging for erosion lifetime and non-contamination performance of tokamak reactor high-Z plasma facing components.« less

Developing ribonucleic acid interference technology to manage whitefly-transmitted begomoviruses

USDA-ARS?s Scientific Manuscript database

Of nearly 300 viruses transmitted by the whitefly (Bemisia tabaci), 90% of them belong to the genus Begomovirus. Begomoviruses are efficiently transmitted by whiteflies to a range of agricultural crops. This results in billions of dollars lost annually, while jeopardizing food security worldwide. Se...

Molecular characterization of true morels (Morchella) in Turkey

USDA-ARS?s Scientific Manuscript database

A collection of 247 true morels (Morchella spp.) was made from 10 different provinces of Turkey during the 2007-2008 growing season. This collection was analyzed for species diversity using phylogenetic analyses of partial Ribonucleic acid (RNA) polymerase I (RPB1) and nuclear ribosomal large subuni...

Identification and initial characterization of a novel turkey-origin picobirnavirus using a metagenomic approach

USDA-ARS?s Scientific Manuscript database

Using the Genome Sequencer FLX Titanium technology (Roche, 454 Life Sciences), a ribonucleic acid (RNA) virus-specific metagenome was prepared using the pooled intestinal contents collected from North Carolina turkey flocks experiencing enteric disease signs. This analysis produced 6526 contigs rang...

Regulation of a maize HD-ZIP IV transcription factor by a non-conventional RDR2-dependent small RNA.

PubMed

Klein-Cosson, Catherine; Chambrier, Pierre; Rogowsky, Peter M; Vernoud, Vanessa

2015-03-01

Small non-coding RNAs are versatile riboregulators that control gene expression at the transcriptional or post-transcriptional level, governing many facets of plant development. Here we present evidence for the existence of a 24 nt small RNA (named small1) that is complementary to the 3' UTR of OCL1 (Outer Cell Layer1), the founding member of the maize HD-ZIP IV gene family encoding plant-specific transcription factors that are mainly involved in epidermis differentiation and specialization. The biogenesis of small1 depends on DICER-like 3 (DCL3), RNA-dependent RNA polymerase 2 (RDR2) and RNA polymerase IV, components that are usually required for RNA-dependent DNA-methylation. Unexpectedly, GFP sensor experiments in transient and stable transformation systems revealed that small1 may regulate its target at the post-transcriptional level, mainly through translational repression. This translational repression is attenuated in an rdr2 mutant background in which small1 does not accumulate. Our experiments further showed the possible involvement of a secondary stem-loop structure present in the 3' UTR of OCL1 for efficient target repression, suggesting the existence of several regulatory mechanisms affecting OCL1 mRNA stability and translation. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Functions and impact of tal-like genes in animals with regard to applied aspects.

PubMed

Zhu, Min; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

2018-06-16

A large number of DNAs in eukaryote genomes can code for atypical transcripts, and their functions are controversial. It has been reported that the transcripts contain many small open reading frames (sORFs), which were originally considered as non-translatable RNAs. However, increasing evidence has suggested that some of these sORFs can encode for small peptides and some are conserved across large evolutionary distances. It has been reported that the small peptides have functions and may be involved in varieties of cellular processes, playing important roles in development, physiology, and metabolism. Among the sORFs, studies of the non-canonical gene polished rice/tarsal-less (pri/tal) in Drosophila and mille-pattes(mlpt) in Tribolium have been more thoroughly studied. The genes similar to pri/tal in other species have been defined as the tarsal-less-related gene family, tal-like gene. In this review, we described recent progress in the discovery and functional characterization of the small peptides encoded by the tal-like gene and their possible functional potentials.

Fundamental Approaches in Molecular Biology for Communication Sciences and Disorders

ERIC Educational Resources Information Center

Bartlett, Rebecca S.; Jette, Marie E.; King, Suzanne N.; Schaser, Allison; Thibeault, Susan L.

2012-01-01

Purpose: This contemporary tutorial will introduce general principles of molecular biology, common deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein assays and their relevance in the field of communication sciences and disorders. Method: Over the past 2 decades, knowledge of the molecular pathophysiology of human disease has…

The effect of dopants on laser imprint mitigation

NASA Astrophysics Data System (ADS)

Phillips, Lee; Gardner, John H.; Bodner, Stephen E.; Colombant, Denis; Dahlburg, Jill

1999-11-01

An intact implosion of a pellet for direct-drive ICF requires that the perturbations imprinted by the laser be kept below some threshold. We report on simulations of targets that incorporate very small concentrations of a high-Z dopant in the ablator, to increase the electron density in the ablating plasma, causing the laser to be absorbed far enough from the solid ablator to achieve a substantial degree of thermal smoothing. These calculations were performed using NRL's FAST radiation hydrodynamics code(J.H. Gardner, A.J. Schmitt, et al., Phys. Plasmas) 5, 1935 (1998), incorporating the flux-corrected transport algorithm and opacities generated by an STA code, with non-LTE radiation transport based on the Busquet method.

The histone variant H2A.Z promotes efficient cotranscriptional splicing in S. cerevisiae

PubMed Central

Neves, Lauren T.; Douglass, Stephen; Spreafico, Roberto; Venkataramanan, Srivats; Kress, Tracy L.; Johnson, Tracy L.

2017-01-01

In eukaryotes, a dynamic ribonucleic protein machine known as the spliceosome catalyzes the removal of introns from premessenger RNA (pre-mRNA). Recent studies show the processes of RNA synthesis and RNA processing to be spatio–temporally coordinated, indicating that RNA splicing takes place in the context of chromatin. H2A.Z is a highly conserved histone variant of the canonical histone H2A. In Saccharomyces cerevisiae, H2A.Z is deposited into chromatin by the SWR-C complex, is found near the 5′ ends of protein-coding genes, and has been implicated in transcription regulation. Here we show that splicing of intron-containing genes in cells lacking H2A.Z is impaired, particularly under suboptimal splicing conditions. Cells lacking H2A.Z are especially dependent on a functional U2 snRNP (small nuclear RNA [snRNA] plus associated proteins), as H2A.Z shows extensive genetic interactions with U2 snRNP-associated proteins, and RNA sequencing (RNA-seq) reveals that introns with nonconsensus branch points are particularly sensitive to H2A.Z loss. Consistently, H2A.Z promotes efficient spliceosomal rearrangements involving the U2 snRNP, as H2A.Z loss results in persistent U2 snRNP association and decreased recruitment of downstream snRNPs to nascent RNA. H2A.Z impairs transcription elongation, suggesting that spliceosome rearrangements are tied to H2A.Z's role in elongation. Depletion of disassembly factor Prp43 suppresses H2A.Z-mediated splice defects, indicating that, in the absence of H2A.Z, stalled spliceosomes are disassembled, and unspliced RNAs are released. Together, these data demonstrate that H2A.Z is required for efficient pre-mRNA splicing and indicate a role for H2A.Z in coordinating the kinetics of transcription elongation and splicing. PMID:28446598

Automated and fast building of three-dimensional RNA structures.

PubMed

Zhao, Yunjie; Huang, Yangyu; Gong, Zhou; Wang, Yanjie; Man, Jianfen; Xiao, Yi

2012-01-01

Building tertiary structures of non-coding RNA is required to understand their functions and design new molecules. Current algorithms of RNA tertiary structure prediction give satisfactory accuracy only for small size and simple topology and many of them need manual manipulation. Here, we present an automated and fast program, 3dRNA, for RNA tertiary structure prediction with reasonable accuracy for RNAs of larger size and complex topology.

CHOOSING A FORM OF BUSINESS ORGANIZATION.

DTIC Science & Technology

Contents: Non-tax considerations in the choice of business form Tax considerations in the choice of a form of business association Tax control and...choice of business form Subchapter S corporations (Int. Rev. Code of 1954, paragraphs 1371-77), permitting shareholders of small business corporations...to be taxed directly on the corpora tion’s earnings rather than have the corporation taxed as an entity at normal corporate rates Choice of business

Prediction of plant lncRNA by ensemble machine learning classifiers.

PubMed

Simopoulos, Caitlin M A; Weretilnyk, Elizabeth A; Golding, G Brian

2018-05-02

In plants, long non-protein coding RNAs are believed to have essential roles in development and stress responses. However, relative to advances on discerning biological roles for long non-protein coding RNAs in animal systems, this RNA class in plants is largely understudied. With comparatively few validated plant long non-coding RNAs, research on this potentially critical class of RNA is hindered by a lack of appropriate prediction tools and databases. Supervised learning models trained on data sets of mostly non-validated, non-coding transcripts have been previously used to identify this enigmatic RNA class with applications largely focused on animal systems. Our approach uses a training set comprised only of empirically validated long non-protein coding RNAs from plant, animal, and viral sources to predict and rank candidate long non-protein coding gene products for future functional validation. Individual stochastic gradient boosting and random forest classifiers trained on only empirically validated long non-protein coding RNAs were constructed. In order to use the strengths of multiple classifiers, we combined multiple models into a single stacking meta-learner. This ensemble approach benefits from the diversity of several learners to effectively identify putative plant long non-coding RNAs from transcript sequence features. When the predicted genes identified by the ensemble classifier were compared to those listed in GreeNC, an established plant long non-coding RNA database, overlap for predicted genes from Arabidopsis thaliana, Oryza sativa and Eutrema salsugineum ranged from 51 to 83% with the highest agreement in Eutrema salsugineum. Most of the highest ranking predictions from Arabidopsis thaliana were annotated as potential natural antisense genes, pseudogenes, transposable elements, or simply computationally predicted hypothetical protein. Due to the nature of this tool, the model can be updated as new long non-protein coding transcripts are identified and functionally verified. This ensemble classifier is an accurate tool that can be used to rank long non-protein coding RNA predictions for use in conjunction with gene expression studies. Selection of plant transcripts with a high potential for regulatory roles as long non-protein coding RNAs will advance research in the elucidation of long non-protein coding RNA function.

The role of sequence in altering the unfolding pathway of an RNA pseudoknot: a steered molecular dynamics study.

PubMed

Gupta, Asmita; Bansal, Manju

2016-10-19

Mechanical unfolding studies on Ribonucleic Acid (RNA) structures are a subject of tremendous interest as they shed light on the principles of higher order assembly of these structures. Pseudoknotting is one of the most elementary ways in which this higher order assembly is achieved as discrete secondary structural units in RNA are brought in close proximity to form a tertiary structure. Using steered molecular dynamics (SMD) simulations, we have studied the unfolding of five RNA pseudoknot structures that differ from each other either by base substitutions in helices or loops. Our SMD simulations reveal the manner in which a biologically functional RNA pseudoknot unfolds and the effect of changes in the primary structure on this unfolding pathway, providing necessary insights into the driving forces behind the functioning of these structures. We observed that an A → C mutation in the loop sequence makes the pseudoknot far more resistant against force induced disruption relative to its wild type structure. In contrast to this, a base-pair substitution GC → AU near the pseudoknot junction region renders it more vulnerable to this disruption. The quantitative estimation of differences in the unfolding paths was carried out using force extension curves, potential of mean force profiles, and the opening of different Watson-Crick and non-Watson-Crick interactions. The results provide a quantified view in which the unfolding paths of the small RNA structures can be used for investigating the programmability of RNA chains for designing RNA switches and aptamers as their biological folding and unfolding could be assessed and manipulated.

Statistical properties of DNA sequences

NASA Technical Reports Server (NTRS)

Peng, C. K.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Mantegna, R. N.; Simons, M.; Stanley, H. E.

1995-01-01

We review evidence supporting the idea that the DNA sequence in genes containing non-coding regions is correlated, and that the correlation is remarkably long range--indeed, nucleotides thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationarity" feature of the sequence of base pairs by applying a new algorithm called detrended fluctuation analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and non-coding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to every DNA sequence (33301 coding and 29453 non-coding) in the entire GenBank database. Finally, we describe briefly some recent work showing that the non-coding sequences have certain statistical features in common with natural and artificial languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts. These statistical properties of non-coding sequences support the possibility that non-coding regions of DNA may carry biological information.

Long non-coding RNA LINC00339 facilitates the tumorigenesis of non-small cell lung cancer by sponging miR-145 through targeting FOXM1.

PubMed

Yuan, Yuan; Haiying, Gao; Zhuo, Li; Ying, Lu; Xin, He

2018-06-12

Non-small cell lung cancer (NSCLC) is one of leading causes of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) has been identified to modulate the tumorigenesis of NSCLC. However, the precise molecular mechanism of lncRNAs in the course is still unclear. Results showed that LINC00339 was significantly up-regulated in NSCLC tissue and cells, which indicated the poor prognosis of NSCLC patients. Loss-of-function experiments showed that LINC00339 silencing inhibited the proliferation and invasion, accelerated the apoptosis, and suppressed the tumor growth of NSCLC cells in vitro and in vivo. Luciferase reporter assay and RNA immunoprecipitation (RIP) revealed that LINC00339 promoted the NSCLC progression via FOXM1 via targeting miR-145. In conclusion, our results identify the important role of the LINC00339/miR-145/FOXM1 axis in the NSCLC tumorigenesis, providing neoteric mechanism for the NSCLC tumorigenesis. Copyright © 2018. Published by Elsevier Masson SAS.

Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria

NASA Astrophysics Data System (ADS)

Teimouri, Hamid; Korkmazhan, Elgin; Stavans, Joel; Levine, Erel

2017-10-01

Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA. We also identify conditions where the sub-cellular organization of cofactors in the sRNA pathway can induce spatial heterogeneity on sRNA targets. Our results suggest that under certain conditions, interpretation and modeling of natural and synthetic gene regulatory circuits need to take into account the spatial organization of the transcripts of participating genes.

76 FR 53912 - FDA's Public Database of Products With Orphan-Drug Designation: Replacing Non-Informative Code...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] FDA's Public Database of Products With Orphan-Drug Designation: Replacing Non-Informative Code Names... replaced non- informative code names with descriptive identifiers on its public database of products that... on our public database with non-informative code names. After careful consideration of this matter...

Facts and updates about cardiovascular non-coding RNAs in heart failure.

PubMed

Thum, Thomas

2015-09-01

About 11% of all deaths include heart failure as a contributing cause. The annual cost of heart failure amounts to US $34,000,000,000 in the United States alone. With the exception of heart transplantation, there is no curative therapy available. Only occasionally there are new areas in science that develop into completely new research fields. The topic on non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, is such a field. In this short review, we will discuss the latest developments about non-coding RNAs in cardiovascular disease. MicroRNAs are short regulatory non-coding endogenous RNA species that are involved in virtually all cellular processes. Long non-coding RNAs also regulate gene and protein levels; however, by much more complicated and diverse mechanisms. In general, non-coding RNAs have been shown to be of great value as therapeutic targets in adverse cardiac remodelling and also as diagnostic and prognostic biomarkers for heart failure. In the future, non-coding RNA-based therapeutics are likely to enter the clinical reality offering a new treatment approach of heart failure.

Transcription start site associated RNAs (TSSaRNAs) are ubiquitous in all domains of life.

PubMed

Zaramela, Livia S; Vêncio, Ricardo Z N; ten-Caten, Felipe; Baliga, Nitin S; Koide, Tie

2014-01-01

A plethora of non-coding RNAs has been discovered using high-resolution transcriptomics tools, indicating that transcriptional and post-transcriptional regulation is much more complex than previously appreciated. Small RNAs associated with transcription start sites of annotated coding regions (TSSaRNAs) are pervasive in both eukaryotes and bacteria. Here, we provide evidence for existence of TSSaRNAs in several archaeal transcriptomes including: Halobacterium salinarum, Pyrococcus furiosus, Methanococcus maripaludis, and Sulfolobus solfataricus. We validated TSSaRNAs from the model archaeon Halobacterium salinarum NRC-1 by deep sequencing two independent small-RNA enriched (RNA-seq) and a primary-transcript enriched (dRNA-seq) strand-specific libraries. We identified 652 transcripts, of which 179 were shown to be primary transcripts (∼7% of the annotated genome). Distinct growth-associated expression patterns between TSSaRNAs and their cognate genes were observed, indicating a possible role in environmental responses that may result from RNA polymerase with varying pausing rhythms. This work shows that TSSaRNAs are ubiquitous across all domains of life.

Characterization of Non-coding DNA Satellites Associated with Sweepoviruses (Genus Begomovirus, Geminiviridae) – Definition of a Distinct Class of Begomovirus-Associated Satellites

PubMed Central

Lozano, Gloria; Trenado, Helena P.; Fiallo-Olivé, Elvira; Chirinos, Dorys; Geraud-Pouey, Francis; Briddon, Rob W.; Navas-Castillo, Jesús

2016-01-01

Begomoviruses (family Geminiviridae) are whitefly-transmitted, plant-infecting single-stranded DNA viruses that cause crop losses throughout the warmer parts of the World. Sweepoviruses are a phylogenetically distinct group of begomoviruses that infect plants of the family Convolvulaceae, including sweet potato (Ipomoea batatas). Two classes of subviral molecules are often associated with begomoviruses, particularly in the Old World; the betasatellites and the alphasatellites. An analysis of sweet potato and Ipomoea indica samples from Spain and Merremia dissecta samples from Venezuela identified small non-coding subviral molecules in association with several distinct sweepoviruses. The sequences of 18 clones were obtained and found to be structurally similar to tomato leaf curl virus-satellite (ToLCV-sat, the first DNA satellite identified in association with a begomovirus), with a region with significant sequence identity to the conserved region of betasatellites, an A-rich sequence, a predicted stem–loop structure containing the nonanucleotide TAATATTAC, and a second predicted stem–loop. These sweepovirus-associated satellites join an increasing number of ToLCV-sat-like non-coding satellites identified recently. Although sharing some features with betasatellites, evidence is provided to suggest that the ToLCV-sat-like satellites are distinct from betasatellites and should be considered a separate class of satellites, for which the collective name deltasatellites is proposed. PMID:26925037

Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening

PubMed Central

Dostie, Josée; Lemire, Edmond; Bouchard, Philippe; Field, Michael; Jones, Kristie; Lorenz, Birgit; Menten, Björn; Buysse, Karen; Pattyn, Filip; Friedli, Marc; Ucla, Catherine; Rossier, Colette; Wyss, Carine; Speleman, Frank; De Paepe, Anne; Dekker, Job; Antonarakis, Stylianos E.; De Baere, Elfride

2009-01-01

To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5′ to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular. PMID:19543368

Non-coding RNA in cystic fibrosis.

PubMed

Glasgow, Arlene M A; De Santi, Chiara; Greene, Catherine M

2018-05-09

Non-coding RNAs (ncRNAs) are an abundant class of RNAs that include small ncRNAs, long non-coding RNAs (lncRNA) and pseudogenes. The human ncRNA atlas includes thousands of these specialised RNA molecules that are further subcategorised based on their size or function. Two of the more well-known and widely studied ncRNA species are microRNAs (miRNAs) and lncRNAs. These are regulatory RNAs and their altered expression has been implicated in the pathogenesis of a variety of human diseases. Failure to express a functional cystic fibrosis (CF) transmembrane receptor (CFTR) chloride ion channel in epithelial cells underpins CF. Secondary to the CFTR defect, it is known that other pathways can be altered and these may contribute to the pathophysiology of CF lung disease in particular. For example, quantitative alterations in expression of some ncRNAs are associated with CF. In recent years, there has been a series of published studies exploring ncRNA expression and function in CF. The majority have focussed principally on miRNAs, with just a handful of reports to date on lncRNAs. The present study reviews what is currently known about ncRNA expression and function in CF, and discusses the possibility of applying this knowledge to the clinical management of CF in the near future. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Mass spectrometric detection of siRNA in plasma samples for doping control purposes.

PubMed

Kohler, Maxie; Thomas, Andreas; Walpurgis, Katja; Schänzer, Wilhelm; Thevis, Mario

2010-10-01

Small interfering ribonucleic acid (siRNA) molecules can effect the expression of any gene by inducing the degradation of mRNA. Therefore, these molecules can be of interest for illicit performance enhancement in sports by affecting different metabolic pathways. An example of an efficient performance-enhancing gene knockdown is the myostatin gene that regulates muscle growth. This study was carried out to provide a tool for the mass spectrometric detection of modified and unmodified siRNA from plasma samples. The oligonucleotides are purified by centrifugal filtration and the use of an miRNA purification kit, followed by flow-injection analysis using an Exactive mass spectrometer to yield the accurate masses of the sense and antisense strands. Although chromatography and sensitive mass spectrometric analysis of oligonucleotides are still challenging, a method was developed and validated that has adequate sensitivity (limit of detection 0.25-1 nmol mL(-1)) and performance (precision 11-21%, recovery 23-67%) for typical antisense oligonucleotides currently used in clinical studies.

Direct-acting Antivirals and Host-targeting Agents against the Hepatitis A Virus

PubMed Central

Kanda, Tatsuo; Nakamoto, Shingo; Wu, Shuang; Nakamura, Masato; Jiang, Xia; Haga, Yuki; Sasaki, Reina; Yokosuka, Osamu

2015-01-01

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs). Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection. Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication. Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication. Based on this review, both DAAs and HTAs may be needed to control effectively HAV infection, and their use should continue to be explored. PMID:26623267

Creating reference gene annotation for the mouse C57BL6/J genome assembly.

PubMed

Mudge, Jonathan M; Harrow, Jennifer

2015-10-01

Annotation on the reference genome of the C57BL6/J mouse has been an ongoing project ever since the draft genome was first published. Initially, the principle focus was on the identification of all protein-coding genes, although today the importance of describing long non-coding RNAs, small RNAs, and pseudogenes is recognized. Here, we describe the progress of the GENCODE mouse annotation project, which combines manual annotation from the HAVANA group with Ensembl computational annotation, alongside experimental and in silico validation pipelines from other members of the consortium. We discuss the more recent incorporation of next-generation sequencing datasets into this workflow, including the usage of mass-spectrometry data to potentially identify novel protein-coding genes. Finally, we will outline how the C57BL6/J genebuild can be used to gain insights into the variant sites that distinguish different mouse strains and species.

Outcome of patients identified as dead (beyond resuscitation) at the point of the emergency call.

PubMed

Harvey, L; Woollard, M

2004-05-01

Currently, an emergency ambulance is dispatched to all cardiac arrest victims. This study aimed to determine the outcome of patients with a dispatch code of 09B01 ("obvious death") and considers the appropriateness of dispatching a non-emergency response. Dispatch records, patient report forms, and hospital records were reviewed to determine patient outcome. Within the one year study period 141 emergency calls were coded as 09B01. Records were obtained for 59 of these cases (42%). Ambulance crews diagnosed 54 as beyond resuscitation (91.5%, 95% CI 79.5% to 96.2%). Three received resuscitation attempts (5.1%, 95% CI 1.1% to 14.2%): two were subsequently pronounced dead at scene and one on arrival at hospital. Two patients were not in cardiac arrest (3.4%, 95% CI 0.4% to 11.7%): one was a transiently unconscious assault victim, and one had a hand injury after a road accident. Three patients coded as 09B01 were transported to hospital for treatment other than confirmation of death (5.1%, 95% CI 1.1% to 14.2%). Not all patients coded 09B01 by dispatchers are assessed as "dead beyond resuscitation" by attending ambulance crews. Although poor data recovery and a small sample size limited the study, its findings suggest that it is inappropriate to allocate a non-emergency response to 09B01 (obvious death) calls.

Methionine-Mediated Repression in Saccharomyces cerevisiae: a Pleiotropic Regulatory System Involving Methionyl Transfer Ribonucleic Acid and the Product of Gene eth2

PubMed Central

Cherest, H.; Surdin-Kerjan, Y.; De Robichon-Szulmajster, H.

1971-01-01

Detailed study of methionine-mediated repression of enzymes involved in methionine biosynthesis in Saccharomyces cerevisiae led to classification of these enzymes into two distinct regulatory groups. Group I comprises four enzymes specifically involved in different parts of methionine biosynthesis, namely, homoserine-O-transacetylase, homocysteine synthetase, adenosine triphosphate sulfurylase, and sulfite reductase. Repressibility of these enzymes is greatly decreased in strains carrying a genetically impaired methionyl-transfer ribonucleic acid (tRNA) synthetase (mutation ts− 296). Conditions leading to absence of repression in the mutant strain have been correlated with a sharp decrease in bulk tRNAmet charging, whereas conditions which restore repressibility of group I enzymes also restore tRNAmet charging. These findings implicate methionyl-tRNA in the regulatory process. However, the absence of a correlation in the wild type between methionyl-tRNA charging and the levels of methionine group I enzymes suggests that only a minor iso accepting species of tRNAmet may be devoted with a regulatory function. Repressibility of the same four enzymes (group I) was also decreased in strains carrying the regulatory mutation eth2r. Although structural genes coding for two of these enzymes, as well as mutations ts− 296 and eth2r segregate independently to each other, synthesis of group I enzymes is coordinated. The pleiotropic regulatory system involved seems then to comprise beside a “regulatory methionyl tRNAmet,” another element, product of gene eth2, which might correspond either to an aporepressor protein or to the “regulatory tRNAmet” itself. Regulation of group II enzymes is defined by response to exogenous methionine, absence of response to either mutations ts− 296 and eth2r, and absence of coordinacy with group I enzymes. However, the two enzymes which belong to this group and are both involved in threonine and methionine biosynthesis undergo distinct regulatory patterns. One, aspartokinase, is subject to a bivalent repression exerted by threonine and methionine, and the other, homoserine dehydrogenase, is subject only to methionine-mediated repression. Participation of at least another aporepressor and another corepressor, different from the ones involved in regulation of group I enzymes, is discussed. PMID:5557593

Preparation of highly multiplexed small RNA sequencing libraries.

PubMed

Persson, Helena; Søkilde, Rolf; Pirona, Anna Chiara; Rovira, Carlos

2017-08-01

MicroRNAs (miRNAs) are ~22-nucleotide-long small non-coding RNAs that regulate the expression of protein-coding genes by base pairing to partially complementary target sites, preferentially located in the 3´ untranslated region (UTR) of target mRNAs. The expression and function of miRNAs have been extensively studied in human disease, as well as the possibility of using these molecules as biomarkers for prognostication and treatment guidance. To identify and validate miRNAs as biomarkers, their expression must be screened in large collections of patient samples. Here, we develop a scalable protocol for the rapid and economical preparation of a large number of small RNA sequencing libraries using dual indexing for multiplexing. Combined with the use of off-the-shelf reagents, more samples can be sequenced simultaneously on large-scale sequencing platforms at a considerably lower cost per sample. Sample preparation is simplified by pooling libraries prior to gel purification, which allows for the selection of a narrow size range while minimizing sample variation. A comparison with publicly available data from benchmarking of miRNA analysis platforms showed that this method captures absolute and differential expression as effectively as commercially available alternatives.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

A Catalogue of Putative cis-Regulatory Interactions Between Long Non-coding RNAs and Proximal Coding Genes Based on Correlative Analysis Across Diverse Human Tumors.

PubMed

Basu, Swaraj; Larsson, Erik

2018-05-31

Antisense transcripts and other long non-coding RNAs are pervasive in mammalian cells, and some of these molecules have been proposed to regulate proximal protein-coding genes in cis For example, non-coding transcription can contribute to inactivation of tumor suppressor genes in cancer, and antisense transcripts have been implicated in the epigenetic inactivation of imprinted genes. However, our knowledge is still limited and more such regulatory interactions likely await discovery. Here, we make use of available gene expression data from a large compendium of human tumors to generate hypotheses regarding non-coding-to-coding cis -regulatory relationships with emphasis on negative associations, as these are less likely to arise for reasons other than cis -regulation. We document a large number of possible regulatory interactions, including 193 coding/non-coding pairs that show expression patterns compatible with negative cis -regulation. Importantly, by this approach we capture several known cases, and many of the involved coding genes have known roles in cancer. Our study provides a large catalog of putative non-coding/coding cis -regulatory pairs that may serve as a basis for further experimental validation and characterization. Copyright © 2018 Basu and Larsson.

Mimicry technology: suppressing small RNA activity in plants.

PubMed

Rubio-Somoza, Ignacio; Manavella, Pablo Andrés

2011-01-01

Small RNA suppression constitutes one of the major difficulties for a full molecular characterization of their specific roles in plants. Taking advantage of the latest insights into the new post-biogenesis layer of regulation in microRNA (miRNA) activity, it is possible to overcome the above-mentioned limitation (Nat Genet 39:1033-1037, 2007). We engineered the IPS1 non-coding RNA to bear a complementary sequence to a given miRNA family, resulting in specific sequestration of RISC complexes. MIMIC technology allows for the constitutive release of all of the potential targets of a miRNA family as well as tissue-specific and inducible suppression of its activity.

Transcriptome-Wide Analysis of UTRs in Non-Small Cell Lung Cancer Reveals Cancer-Related Genes with SNV-Induced Changes on RNA Secondary Structure and miRNA Target Sites

PubMed Central

Novotny, Peter; Tang, Xiaojia; Kalari, Krishna R.; Gorodkin, Jan

2014-01-01

Traditional mutation assessment methods generally focus on predicting disruptive changes in protein-coding regions rather than non-coding regulatory regions like untranslated regions (UTRs) of mRNAs. The UTRs, however, are known to have many sequence and structural motifs that can regulate translational and transcriptional efficiency and stability of mRNAs through interaction with RNA-binding proteins and other non-coding RNAs like microRNAs (miRNAs). In a recent study, transcriptomes of tumor cells harboring mutant and wild-type KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) genes in patients with non-small cell lung cancer (NSCLC) have been sequenced to identify single nucleotide variations (SNVs). About 40% of the total SNVs (73,717) identified were mapped to UTRs, but omitted in the previous analysis. To meet this obvious demand for analysis of the UTRs, we designed a comprehensive pipeline to predict the effect of SNVs on two major regulatory elements, secondary structure and miRNA target sites. Out of 29,290 SNVs in 6462 genes, we predict 472 SNVs (in 408 genes) affecting local RNA secondary structure, 490 SNVs (in 447 genes) affecting miRNA target sites and 48 that do both. Together these disruptive SNVs were present in 803 different genes, out of which 188 (23.4%) were previously known to be cancer-associated. Notably, this ratio is significantly higher (one-sided Fisher's exact test p-value = 0.032) than the ratio (20.8%) of known cancer-associated genes (n = 1347) in our initial data set (n = 6462). Network analysis shows that the genes harboring disruptive SNVs were involved in molecular mechanisms of cancer, and the signaling pathways of LPS-stimulated MAPK, IL-6, iNOS, EIF2 and mTOR. In conclusion, we have found hundreds of SNVs which are highly disruptive with respect to changes in the secondary structure and miRNA target sites within UTRs. These changes hold the potential to alter the expression of known cancer genes or genes linked to cancer-associated pathways. PMID:24416147

Transcriptome-wide analysis of UTRs in non-small cell lung cancer reveals cancer-related genes with SNV-induced changes on RNA secondary structure and miRNA target sites.

PubMed

Sabarinathan, Radhakrishnan; Wenzel, Anne; Novotny, Peter; Tang, Xiaojia; Kalari, Krishna R; Gorodkin, Jan

2014-01-01

Traditional mutation assessment methods generally focus on predicting disruptive changes in protein-coding regions rather than non-coding regulatory regions like untranslated regions (UTRs) of mRNAs. The UTRs, however, are known to have many sequence and structural motifs that can regulate translational and transcriptional efficiency and stability of mRNAs through interaction with RNA-binding proteins and other non-coding RNAs like microRNAs (miRNAs). In a recent study, transcriptomes of tumor cells harboring mutant and wild-type KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) genes in patients with non-small cell lung cancer (NSCLC) have been sequenced to identify single nucleotide variations (SNVs). About 40% of the total SNVs (73,717) identified were mapped to UTRs, but omitted in the previous analysis. To meet this obvious demand for analysis of the UTRs, we designed a comprehensive pipeline to predict the effect of SNVs on two major regulatory elements, secondary structure and miRNA target sites. Out of 29,290 SNVs in 6462 genes, we predict 472 SNVs (in 408 genes) affecting local RNA secondary structure, 490 SNVs (in 447 genes) affecting miRNA target sites and 48 that do both. Together these disruptive SNVs were present in 803 different genes, out of which 188 (23.4%) were previously known to be cancer-associated. Notably, this ratio is significantly higher (one-sided Fisher's exact test p-value = 0.032) than the ratio (20.8%) of known cancer-associated genes (n = 1347) in our initial data set (n = 6462). Network analysis shows that the genes harboring disruptive SNVs were involved in molecular mechanisms of cancer, and the signaling pathways of LPS-stimulated MAPK, IL-6, iNOS, EIF2 and mTOR. In conclusion, we have found hundreds of SNVs which are highly disruptive with respect to changes in the secondary structure and miRNA target sites within UTRs. These changes hold the potential to alter the expression of known cancer genes or genes linked to cancer-associated pathways.

cncRNAs: Bi-functional RNAs with protein coding and non-coding functions

PubMed Central

Kumari, Pooja; Sampath, Karuna

2015-01-01

For many decades, the major function of mRNA was thought to be to provide protein-coding information embedded in the genome. The advent of high-throughput sequencing has led to the discovery of pervasive transcription of eukaryotic genomes and opened the world of RNA-mediated gene regulation. Many regulatory RNAs have been found to be incapable of protein coding and are hence termed as non-coding RNAs (ncRNAs). However, studies in recent years have shown that several previously annotated non-coding RNAs have the potential to encode proteins, and conversely, some coding RNAs have regulatory functions independent of the protein they encode. Such bi-functional RNAs, with both protein coding and non-coding functions, which we term as ‘cncRNAs’, have emerged as new players in cellular systems. Here, we describe the functions of some cncRNAs identified from bacteria to humans. Because the functions of many RNAs across genomes remains unclear, we propose that RNAs be classified as coding, non-coding or both only after careful analysis of their functions. PMID:26498036

Quantitative spectroscopy of extreme helium stars Model atmospheres and a non-LTE abundance analysis of BD+10°2179

NASA Astrophysics Data System (ADS)

Kupfer, T.; Przybilla, N.; Heber, U.; Jeffery, C. S.; Behara, N. T.; Butler, K.

2017-10-01

Extreme helium stars (EHe stars) are hydrogen-deficient supergiants of spectral type A and B. They are believed to result from mergers in double degenerate systems. In this paper, we present a detailed quantitative non-LTE spectral analysis for BD+10°2179, a prototype of this rare class of stars, using UV-Visual Echelle Spectrograph and Fiber-fed Extended Range Optical Spectrograph spectra covering the range from ˜3100 to 10 000 Å. Atmosphere model computations were improved in two ways. First, since the UV metal line blanketing has a strong impact on the temperature-density stratification, we used the atlas12 code. Additionally, We tested atlas12 against the benchmark code sterne3, and found only small differences in the temperature and density stratifications, and good agreement with the spectral energy distributions. Secondly, 12 chemical species were treated in non-LTE. Pronounced non-LTE effects occur in individual spectral lines but, for the majority, the effects are moderate to small. The spectroscopic parameters give Teff =17 300±300 K and log g = 2.80±0.10, and an evolutionary mass of 0.55±0.05 M⊙. The star is thus slightly hotter, more compact and less massive than found in previous studies. The kinematic properties imply a thick-disc membership, which is consistent with the metallicity [Fe/H] ≈ -1 and α-enhancement. The refined light-element abundances are consistent with the white dwarf merger scenario. We further discuss the observed helium spectrum in an appendix, detecting dipole-allowed transitions from about 150 multiplets plus the most comprehensive set of known/predicted isolated forbidden components to date. Moreover, a so far unreported series of pronounced forbidden He I components is detected in the optical-UV.

A Contemporary, Laboratory-Intensive Course on Messenger RNA Transcription and Processing

ERIC Educational Resources Information Center

Carson, Sue; Miller, Heather

2012-01-01

Messenger ribonucleic acid (mRNA) plays a pivotal role in the central dogma of molecular biology. Importantly, molecular events occurring during and after mRNA synthesis have the potential to create multiple proteins from one gene, leading to some of the remarkable protein diversity that genomes hold. The North Carolina State University…

Composition of ribonucleic acid from various parts of spider oocytes.

PubMed

EDSTROM, J E

1960-09-01

Microphoretic purine-pyrimidine analyses of the ribonucleic acid (RNA) in nucleoli, nucleoplasm, cytoplasm, and yolk nuclei of spider oocytes have been carried out. The material necessary for the analyses was isolated by micromanipulation. Determinations of the amounts of RNA in the different parts of the cell were also performed. No differences between the composition of RNA in the nucleolus and the cytoplasm could be disclosed. Nucleoplasmic RNA was, on the other hand, distinctly different from that in the nucleolus and in the cytoplasm. The difference lies in the content of adenine, which is highest in nucleoplasmic RNA. The few analyses carried out on yolk nuclei showed their RNA to be variable in composition with a tendency to high purine values. The cytoplasm contains about 99 per cent of the total RNA in these cells, the nucleoplasm about 1 per cent, and the nucleolus not more than 0.3 per cent, although the highest concentrations are found in these latter structures. When considered in the light of other recent findings the results are compatible with the view that nucleolar RNA is the precursor of cytoplasmic RNA.

Evaluating the reproducibility of quantifying modified nucleosides from ribonucleic acids by LC–UV–MS

PubMed Central

Russell, Susan P.; Limbach, Patrick A.

2013-01-01

Post-transcriptional chemical covalent modification of adenosine, guanosine, uridine and cytidine occurs frequently in all types of ribonucleic acids (RNAs). In ribosomal RNA (rRNA) and transfer RNA (tRNA) these modifications make important contributions to RNA structure and stability and to the accuracy and efficiency of protein translation. The functional dynamics, synergistic nature and regulatory roles of these posttranscriptional nucleoside modifications within the cell are not well characterized. These modifications are present at very low levels and isolation of individual nucleosides for analysis requires a complex multi-step approach. The focus of this study is to characterize the reproducibility of a liquid chromatography method used to isolate and quantitatively characterize modified nucleosides in tRNA and rRNA when nucleoside detection is performed using ultraviolet and mass spectrometric detection (UV and MS, respectively). Despite the analytical challenges of sample isolation and dynamic range, quantitative profiling of modified nucleosides obtained from bacterial tRNAs and rRNAs is feasible at relative standard deviations of 5% RSD or less. PMID:23500350

Strain of Escherichia coli with a temperature-sensitive mutation affecting ribosomal ribonucleic acid accumulation.

PubMed Central

Frey, T; Newlin, L L; Atherly, A G

1975-01-01

A mutant of Escherichia coli has been isolated that has a temperature-sensitive mutation that results in specific loss of ribosomal ribonucleic acid (RNA) synthesis and some reduction in messenger RNA synthesis. When the strain was grown in glucose medium at a restrictive temperature, RNA accumulation ceased, but both messenger RNA and protein synthesis continued for an extended time. Because carbon metabolism was slowed drastically when strain AA-157 was placed at the restrictive temperature, this phenotype can be compared with carbon depletion conditions present during diauxic lag. However, the phenotype of mutant AA-157 differs from shift-down conditions in that guanosine-3',5'-tetraphosphate levels are unaffected; therefore, a different site is affected. This mutant strain (AA-157) thus shows many characteristics similar to an aldolase mutant previously reported (Böck and Neidhardt, 1966). However, the mutation occurred in a different position on the E. coli genetic map, and furthermore, aldolase was not temperature sensitive in strain AA-157. In this paper we present a study of macromolecular biosynthesis in this mutant. PMID:1090609

Regulation of ribonucleic acid synthesis by polyamines. Reversal by spermine of inhibition by methylglyoxal bis(guanylhydrazone) of ribonucleic acid synthesis and histone acetylation in rabbit heart.

PubMed

Caldarera, C M; Casti, A; Guarnier, C; Moruzzi, G

1975-10-01

The relationship between polyamines and RNA synthesis was studied by considering the action of spermine on histone acetylation in perfused heart. In addition, the effect of methylglyoxal bis(guanylhydrazone), inhibitor of putrescine-activated S-adenosylmethionine decarboxylase activity, on RNA and polyamine specific radioactivity and on acetylation of histone fractions was also investigated in perfused heart. Different concentrations of spermine and/or methylglyoxas bis(guanylhydrazone) were injected into the heart, 15 min after beginning the perfusion. The results demonstrate that spermine stimulates the specific radioactivity of RNA of subcellular fractions. Acetylation of the arginine-rich histone fractions, involved in the regulation of RNA transcription, is enhanced by spermine. The perfusion with methylglyoxal bis(guanylhydrazone) causes a decrease in the specific radioactivity of polyamines and RNA, and in acetylation of histone fractions. However, spermine is able to reverse the methylglyoxal bis(guanylhydrazone) inhibition when injected simultaneously. From these results we may assume a possible role for spermine in the regulation of RNA transcription.

Regulation of ribonucleic acid synthesis by polyamines. Reversal by spermine of inhibition by methylglyoxal bis(guanylhydrazone) of ribonucleic acid synthesis and histone acetylation in rabbit heart.

PubMed Central

Caldarera, C M; Casti, A; Guarnier, C; Moruzzi, G

1975-01-01

The relationship between polyamines and RNA synthesis was studied by considering the action of spermine on histone acetylation in perfused heart. In addition, the effect of methylglyoxal bis(guanylhydrazone), inhibitor of putrescine-activated S-adenosylmethionine decarboxylase activity, on RNA and polyamine specific radioactivity and on acetylation of histone fractions was also investigated in perfused heart. Different concentrations of spermine and/or methylglyoxas bis(guanylhydrazone) were injected into the heart, 15 min after beginning the perfusion. The results demonstrate that spermine stimulates the specific radioactivity of RNA of subcellular fractions. Acetylation of the arginine-rich histone fractions, involved in the regulation of RNA transcription, is enhanced by spermine. The perfusion with methylglyoxal bis(guanylhydrazone) causes a decrease in the specific radioactivity of polyamines and RNA, and in acetylation of histone fractions. However, spermine is able to reverse the methylglyoxal bis(guanylhydrazone) inhibition when injected simultaneously. From these results we may assume a possible role for spermine in the regulation of RNA transcription. PMID:1212228

Identification and Differential Abundance of Mitochondrial Genome Encoding Small RNAs (mitosRNA) in Breast Muscles of Modern Broilers and Unselected Chicken Breed

PubMed Central

Bottje, Walter G.; Khatri, Bhuwan; Shouse, Stephanie A.; Seo, Dongwon; Mallmann, Barbara; Orlowski, Sara K.; Pan, Jeonghoon; Kong, Seongbae; Owens, Casey M.; Anthony, Nicholas B.; Kim, Jae K.; Kong, Byungwhi C.

2017-01-01

Background: Although small non-coding RNAs are mostly encoded by the nuclear genome, thousands of small non-coding RNAs encoded by the mitochondrial genome, termed as mitosRNAs were recently reported in human, mouse and trout. In this study, we first identified chicken mitosRNAs in breast muscle using small RNA sequencing method and the differential abundance was analyzed between modern pedigree male (PeM) broilers (characterized by rapid growth and large muscle mass) and the foundational Barred Plymouth Rock (BPR) chickens (characterized by slow growth and small muscle mass). Methods: Small RNA sequencing was performed with total RNAs extracted from breast muscles of PeM and BPR (n = 6 per group) using the 1 × 50 bp single end read method of Illumina sequencing. Raw reads were processed by quality assessment, adapter trimming, and alignment to the chicken mitochondrial genome (GenBank Accession: X52392.1) using the NGen program. Further statistical analyses were performed using the JMP Genomics 8. Differentially expressed (DE) mitosRNAs between PeM and BPR were confirmed by quantitative PCR. Results: Totals of 183,416 unique small RNA sequences were identified as potential chicken mitosRNAs. After stringent filtering processes, 117 mitosRNAs showing >100 raw read counts were abundantly produced from all 37 mitochondrial genes (except D-loop region) and the length of mitosRNAs ranged from 22 to 46 nucleotides. Of those, abundance of 44 mitosRNAs were significantly altered in breast muscles of PeM compared to those of BPR: all mitosRNAs were higher in PeM breast except those produced from 16S-rRNA gene. Possibly, the higher mitosRNAs abundance in PeM breast may be due to a higher mitochondrial content compared to BPR. Our data demonstrate that in addition to 37 known mitochondrial genes, the mitochondrial genome also encodes abundant mitosRNAs, that may play an important regulatory role in muscle growth via mitochondrial gene expression control. PMID:29104541

Micro-RNA-21 (biomarker) and global longitudinal strain (functional marker) in detection of myocardial fibrotic burden in severe aortic valve stenosis: a pilot study.

PubMed

Fabiani, Iacopo; Scatena, Cristian; Mazzanti, Chiara Maria; Conte, Lorenzo; Pugliese, Nicola Riccardo; Franceschi, Sara; Lessi, Francesca; Menicagli, Michele; De Martino, Andrea; Pratali, Stefano; Bortolotti, Uberto; Naccarato, Antonio Giuseppe; La Carrubba, Salvatore; Di Bello, Vitantonio

2016-08-27

Myocardial fibrosis (MF) is a deleterious consequence of aortic valve stenosis (AVS). Global longitudinal strain (GLS) is a novel left ventricular (LV) functional parameter potentially useful to non-invasively estimate MF. MicroRNAs (miRNAs) are non-coding small ribonucleic acids (RNA) modulating genes function, mainly through RNA degradation. miRNA-21 is a biomarker associated with MF in pressure overload. The aim of the present study was to find an integrated algorithm for detection of MF using a combined approach with both bio- and functional markers. Thirty-six patients (75.2 ± 8 y.o.; 63 % Female) with severe AVS and preserved LV ejection fraction (EF), candidate to surgical aortic valve replacement (sAVR) were enrolled. Clinical, bio-humoral evaluation (including plasmatic miRNA-21 collected using specific tubes, PAXgene, for stabilization of peripheral RNA) and a complete echocardiographic study, including GLS and septal strain, were performed before sAVR. Twenty-eight of those patients underwent sAVR and, in 23 of them, an inter-ventricular septum biopsy was performed. Tissues were fixed in formalin and embedded in paraffin. Sections were stained with Hematoxylin and Eosin for histological evaluation and with histochemical Masson trichrome for collagen fibers. The different components were calculated and expressed as micrometers(2). To evaluate tissue miRNA components, sections 2-μm thick were cut using a microtome blade for each slide. Regression analysis was performed to test association between dependent variable and various predictors included in the model. Despite a preserved EF (66 ± 11 %), patients presented altered myocardial deformation parameters (GLS -14,02 ± 3.8 %; septal longitudinal strain, SSL -9.63 ± 2.9 %; septal longitudinal strain rate, SL-Sr -0.58 ± 0.17 1/s; Septal Longitudinal early-diastolic strain rate, SL-SrE 0.62 ± 0.32 1/s). The extent of MF showed an inverse association with both GLS and septal longitudinal deformation indices (GLS: R(2) = 0.30; p = 0.02; SSL: R(2) = 0.36; p = 0.01; SL-Sr: R(2) = 0.39; p < 0.001; SL-SrE: R(2) = 0.35; p = 0.001). miRNA-21 was mainly expressed in fibrous tissue (p < 0.0001). A significant association between MF and plasmatic miRNA-21, alone and weighted for measures of structural (LVMi R(2) = 0.50; p = 0.0005) and functional (SSL R(2) = 0.35; p = 0.006) remodeling, was found. In AVS, MF is associated with alterations of regional and global strain. Plasmatic miRNA-21 is directly related to MF and associated with LV structural and functional impairment.

Ground-water quality and discharge to Chincoteague and Sinepuxent Bays adjacent to Assateague Island National Seashore, Maryland

USGS Publications Warehouse

Dillow, Jonathan J.A.; Banks, William S.L.; Smigaj, Michael J.

2002-01-01

The U.S. Geological Survey, in cooperation with the Maryland Department of the Environment and the Wisconsin State Laboratory of Hygiene, conducted a study to characterize the occurrence and distribution of viral contamination in small (withdrawing less than 10,000 gallons per day) public water-supply wells screened in the shallow aquifer in the Piedmont Physiographic Province in Baltimore and Harford Counties, Maryland. Two hundred sixty-three small public water-supply wells were in operation in these counties during the spring of 2000. Ninety-one of these sites were selected for sampling using a methodology that distributed the samples evenly over the population and the spatial extent of the study area. Each site, and its potential susceptibility to microbiological contamination, was evaluated with regard to hole depth, casing interval, and open interval. Each site was evaluated using characteristics such as on-site geology and on-site land use.Samples were collected by pumping between 200 and 400 gallons of untreated well water through an electropositive cartridge filter. Water concentrates were subjected to cell-culture assay for the detection of culturable viruses and reverse-transcription polymerase chain reaction/gene probe assays to detect viral ribonucleic acid; grab samples were analyzed for somatic and male-specific coliphages, Bacteroides fragilis, Clostridium perfringens, enterococci, Escherichia coli, total coliforms, total oxidized nitrogen, nitrite, organic nitrogen, total phosphate, ortho-phosphate, calcium, magnesium, sodium, potas-sium, chloride, sulfate, iron, acid-neutralizing capacity, pH, specific conductance, temperature, and dissolved oxygen.One sample tested positive for the presence of the ribonucleic acid of rotavirus through poly-merase chain-reaction analysis. Twenty-nine per-cent of the samples (26 of 90) had bacterial con-tamination. About 7 percent of the samples (6 of 90) were contaminated with either male-specific coliphage, somatic coliphage, or bacteriophages of Bacteroides fragilis. About 3 percent of the sam-ples (3 of 87) had oxidized nitrogen concentra-tions that exceeded the U.S. Environmental Protection Agency?s Maximum Contaminant Level of 10.0 milligrams per liter. A statistical analysis showed that no significant relation exists between the presence of bacteria or coliphage and all variables, except the mean temperature of the water sample as measured in the field. Additionally, the concentration of total coliform bacteria had a statistically significant, moderately strong cor-relation with the concentration of sulfate and sample pH as measured at the U.S. Geological Survey National Water-Quality Laboratory in Denver, Colorado.

Occurrence and distribution of microbiological contamination and enteric viruses in shallow ground water in Baltimore and Harford counties, Maryland

USGS Publications Warehouse

Banks, William S.L.; Battigelli, David A.

2002-01-01

The U.S. Geological Survey, in cooperation with the Maryland Department of the Environment and the Wisconsin State Laboratory of Hygiene, conducted a study to characterize the occurrence and distribution of viral contamination in small (withdrawing less than 10,000 gallons per day) public water-supply wells screened in the shallow aquifer in the Piedmont Physiographic Province in Baltimore and Harford Counties, Maryland. Two hundred sixty-three small public water-supply wells were in operation in these counties during the spring of 2000. Ninety-one of these sites were selected for sampling using a methodology that distributed the samples evenly over the population and the spatial extent of the study area. Each site, and its potential susceptibility to microbiological contamination, was evaluated with regard to hole depth, casing interval, and open interval. Each site was evaluated using characteristics such as on-site geology and on-site land use.Samples were collected by pumping between 200 and 400 gallons of untreated well water through an electropositive cartridge filter. Water concentrates were subjected to cell-culture assay for the detection of culturable viruses and reverse-transcription polymerase chain reaction/gene probe assays to detect viral ribonucleic acid; grab samples were analyzed for somatic and male-specific coliphages, Bacteroides fragilis, Clostridium perfringens, enterococci, Escherichia coli, total coliforms, total oxidized nitrogen, nitrite, organic nitrogen, total phosphate, ortho-phosphate, calcium, magnesium, sodium, potas-sium, chloride, sulfate, iron, acid-neutralizing capacity, pH, specific conductance, temperature, and dissolved oxygen.One sample tested positive for the presence of the ribonucleic acid of rotavirus through poly-merase chain-reaction analysis. Twenty-nine per-cent of the samples (26 of 90) had bacterial con-tamination. About 7 percent of the samples (6 of 90) were contaminated with either male-specific coliphage, somatic coliphage, or bacteriophages of Bacteroides fragilis. About 3 percent of the sam-ples (3 of 87) had oxidized nitrogen concentra-tions that exceeded the U.S. Environmental Protection Agency?s Maximum Contaminant Level of 10.0 milligrams per liter. A statistical analysis showed that no significant relation exists between the presence of bacteria or coliphage and all variables, except the mean temperature of the water sample as measured in the field. Additionally, the concentration of total coliform bacteria had a statistically significant, moderately strong cor-relation with the concentration of sulfate and sample pH as measured at the U.S. Geological Survey National Water-Quality Laboratory in Denver, Colorado.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen

Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression,more » and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.« less

Complete Sequence of the mitochondrial genome of the tapeworm Hymenolepis diminuta: Gene arrangements indicate that platyhelminths are eutrochozoans

DOE Office of Scientific and Technical Information (OSTI.GOV)

von Nickisch-Rosenegk, Markus; Brown, Wesley M.; Boore, Jeffrey L.

2001-01-01

Using ''long-PCR'' we have amplified in overlapping fragments the complete mitochondrial genome of the tapeworm Hymenolepis diminuta (Platyhelminthes: Cestoda) and determined its 13,900 nucleotide sequence. The gene content is the same as that typically found for animal mitochondrial DNA (mtDNA) except that atp8 appears to be lacking, a condition found previously for several other animals. Despite the small size of this mtDNA, there are two large non-coding regions, one of which contains 13 repeats of a 31 nucleotide sequence and a potential stem-loop structure of 25 base pairs with an 11-member loop. Large potential secondary structures are identified also formore » the non-coding regions of two other cestode mtDNAs. Comparison of the mitochondrial gene arrangement of H. diminuta with those previously published supports a phylogenetic position of flatworms as members of the Eutrochozoa, rather than being basal to either a clade of protostomes or a clade of coelomates.« less

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

Genome re-annotation of the wild strawberry Fragaria vesca using extensive Illumina- and SMRT-based RNA-seq datasets

PubMed Central

Li, Yongping; Wei, Wei; Feng, Jia; Luo, Huifeng; Pi, Mengting; Liu, Zhongchi; Kang, Chunying

2018-01-01

Abstract The genome of the wild diploid strawberry species Fragaria vesca, an ideal model system of cultivated strawberry (Fragaria × ananassa, octoploid) and other Rosaceae family crops, was first published in 2011 and followed by a new assembly (Fvb). However, the annotation for Fvb mainly relied on ab initio predictions and included only predicted coding sequences, therefore an improved annotation is highly desirable. Here, a new annotation version named v2.0.a2 was created for the Fvb genome by a pipeline utilizing one PacBio library, 90 Illumina RNA-seq libraries, and 9 small RNA-seq libraries. Altogether, 18,641 genes (55.6% out of 33,538 genes) were augmented with information on the 5′ and/or 3′ UTRs, 13,168 (39.3%) protein-coding genes were modified or newly identified, and 7,370 genes were found to possess alternative isoforms. In addition, 1,938 long non-coding RNAs, 171 miRNAs, and 51,714 small RNA clusters were integrated into the annotation. This new annotation of F. vesca is substantially improved in both accuracy and integrity of gene predictions, beneficial to the gene functional studies in strawberry and to the comparative genomic analysis of other horticultural crops in Rosaceae family. PMID:29036429

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering.

PubMed

Ni, PeiYan; Fu, ShaoZhi; Fan, Min; Guo, Gang; Shi, Shuai; Peng, JinRong; Luo, Feng; Qian, ZhiYong

2011-01-01

Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone tissue engineering application, however, the great hydrophobicity limits its broad application. In this study, the hybrid amphiphilic poly(ethylene glycol) (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with regular and continuous fibers compared to corresponding blank PLA fiber mats. The prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment and proliferation by providing an interconnected porous extracellular environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the interstitial pores and integrate well with the surrounding fibers, which is very important for favorable application in tissue engineering. More importantly, the electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate into bone-associated cells by comprehensively evaluating the representative markers of the osteogenic procedure with messenger ribonucleic acid quantitation and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better differentiation potential with higher messenger ribonucleic acid expression of the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I. The significantly higher alkaline phosphatase activity of the PEG/PLA fibrous scaffolds indicated that these can enhance the differentiation of MSCs into osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level of the late osteogenic differentiation markers OCN (osteocalcin) and OPN (osteopontin), accompanied by the positive Alizarin red S staining, showed better maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the mineralization stage of differentiation. After transplantation into the thigh muscle pouches of rats, and evaluating the inflammatory cells surrounding the scaffolds and the physiological characteristics of the surrounding tissues, the PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular response and excellent osteogenic potential in vitro, as well as the biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA fibrous scaffolds could be one of the most promising candidates in bone tissue engineering.

Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs

PubMed Central

2014-01-01

Background The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein-coding RNAs. Despite increasing numbers of functional reports of individual long non-coding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein-coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays. Results We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein-coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed. Conclusions It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events. PMID:24594072

Design and construction of functional AAV vectors.

PubMed

Gray, John T; Zolotukhin, Serge

2011-01-01

Using the basic principles of molecular biology and laboratory techniques presented in this chapter, researchers should be able to create a wide variety of AAV vectors for both clinical and basic research applications. Basic vector design concepts are covered for both protein coding gene expression and small non-coding RNA gene expression cassettes. AAV plasmid vector backbones (available via AddGene) are described, along with critical sequence details for a variety of modular expression components that can be inserted as needed for specific applications. Protocols are provided for assembling the various DNA components into AAV vector plasmids in Escherichia coli, as well as for transferring these vector sequences into baculovirus genomes for large-scale production of AAV in the insect cell production system.

50 CFR Table 14b to Part 679 - Port of Landing Codes: Non-Alaska

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Port of Landing Codes: Non-Alaska 14b... ALASKA Pt. 679, Table 14b Table 14b to Part 679—Port of Landing Codes: Non-Alaska (California, Canada... report a landing at a location not currently assigned a location code number, use the code for “Other...

50 CFR Table 14b to Part 679 - Port of Landing Codes: Non-Alaska

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Port of Landing Codes: Non-Alaska 14b... ALASKA Pt. 679, Table 14b Table 14b to Part 679—Port of Landing Codes: Non-Alaska (California, Canada... report a landing at a location not currently assigned a location code number, use the code for “Other...

OpenGeoSys-GEMS: Hybrid parallelization of a reactive transport code with MPI and threads

NASA Astrophysics Data System (ADS)

Kosakowski, G.; Kulik, D. A.; Shao, H.

2012-04-01

OpenGeoSys-GEMS is a generic purpose reactive transport code based on the operator splitting approach. The code couples the Finite-Element groundwater flow and multi-species transport modules of the OpenGeoSys (OGS) project (http://www.ufz.de/index.php?en=18345) with the GEM-Selektor research package to model thermodynamic equilibrium of aquatic (geo)chemical systems utilizing the Gibbs Energy Minimization approach (http://gems.web.psi.ch/). The combination of OGS and the GEM-Selektor kernel (GEMS3K) is highly flexible due to the object-oriented modular code structures and the well defined (memory based) data exchange modules. Like other reactive transport codes, the practical applicability of OGS-GEMS is often hampered by the long calculation time and large memory requirements. • For realistic geochemical systems which might include dozens of mineral phases and several (non-ideal) solid solutions the time needed to solve the chemical system with GEMS3K may increase exceptionally. • The codes are coupled in a sequential non-iterative loop. In order to keep the accuracy, the time step size is restricted. In combination with a fine spatial discretization the time step size may become very small which increases calculation times drastically even for small 1D problems. • The current version of OGS is not optimized for memory use and the MPI version of OGS does not distribute data between nodes. Even for moderately small 2D problems the number of MPI processes that fit into memory of up-to-date workstations or HPC hardware is limited. One strategy to overcome the above mentioned restrictions of OGS-GEMS is to parallelize the coupled code. For OGS a parallelized version already exists. It is based on a domain decomposition method implemented with MPI and provides a parallel solver for fluid and mass transport processes. In the coupled code, after solving fluid flow and solute transport, geochemical calculations are done in form of a central loop over all finite element nodes with calls to GEMS3K and consecutive calculations of changed material parameters. In a first step the existing MPI implementation was utilized to parallelize this loop. Calculations were split between the MPI processes and afterwards data was synchronized by using MPI communication routines. Furthermore, multi-threaded calculation of the loop was implemented with help of the boost thread library (http://www.boost.org). This implementation provides a flexible environment to distribute calculations between several threads. For each MPI process at least one and up to several dozens of worker threads are spawned. These threads do not replicate the complete OGS-GEM data structure and use only a limited amount of memory. Calculation of the central geochemical loop is shared between all threads. Synchronization between the threads is done by barrier commands. The overall number of local threads times MPI processes should match the number of available computing nodes. The combination of multi-threading and MPI provides an effective and flexible environment to speed up OGS-GEMS calculations while limiting the required memory use. Test calculations on different hardware show that for certain types of applications tremendous speedups are possible.

Long Non-Coding RNAs Differentially Expressed between Normal versus Primary Breast Tumor Tissues Disclose Converse Changes to Breast Cancer-Related Protein-Coding Genes

PubMed Central

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U.; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N.; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O.

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes. PMID:25264628

Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

PubMed

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes.

Targeting Non-Coding RNAs in Plants with the CRISPR-Cas Technology is a Challenge yet Worth Accepting.

PubMed

Basak, Jolly; Nithin, Chandran

2015-01-01

Non-coding RNAs (ncRNAs) have emerged as versatile master regulator of biological functions in recent years. MicroRNAs (miRNAs) are small endogenous ncRNAs of 18-24 nucleotides in length that originates from long self-complementary precursors. Besides their direct involvement in developmental processes, plant miRNAs play key roles in gene regulatory networks and varied biological processes. Alternatively, long ncRNAs (lncRNAs) are a large and diverse class of transcribed ncRNAs whose length exceed that of 200 nucleotides. Plant lncRNAs are transcribed by different RNA polymerases, showing diverse structural features. Plant lncRNAs also are important regulators of gene expression in diverse biological processes. There has been a breakthrough in the technology of genome editing, the CRISPR-Cas9 (clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9) technology, in the last decade. CRISPR loci are transcribed into ncRNA and eventually form a functional complex with Cas9 and further guide the complex to cleave complementary invading DNA. The CRISPR-Cas technology has been successfully applied in model plants such as Arabidopsis and tobacco and important crops like wheat, maize, and rice. However, all these studies are focused on protein coding genes. Information about targeting non-coding genes is scarce. Hitherto, the CRISPR-Cas technology has been exclusively used in vertebrate systems to engineer miRNA/lncRNAs, but it is still relatively unexplored in plants. While briefing miRNAs, lncRNAs and applications of the CRISPR-Cas technology in human and animals, this review essentially elaborates several strategies to overcome the challenges of applying the CRISPR-Cas technology in editing ncRNAs in plants and the future perspective of this field.

Stability of metal-rich very massive stars

NASA Astrophysics Data System (ADS)

Goodman, J.; White, Christopher J.

2016-02-01

We revisit the stability of very massive non-rotating main-sequence stars at solar metallicity, with the goal of understanding whether radial pulsations set a physical upper limit to stellar mass. Models of up to 938 solar masses are constructed with the MESA code, and their linear stability in the fundamental mode, assumed to be the most dangerous, is analysed with a fully non-adiabatic method. Models above 100 M⊙ have extended tenuous atmospheres (`shelves') that affect the stability of the fundamental. Even when positive, this growth rate is small, in agreement with previous results. We argue that small growth rates lead to saturation at small amplitudes that are not dangerous to the star. A mechanism for saturation is demonstrated involving non-linear parametric coupling to short-wavelength g-modes and the damping of the latter by radiative diffusion. The shelves are subject to much more rapidly growing strange modes. This also agrees with previous results but is extended here to higher masses. The strange modes probably saturate via shocks rather than mode coupling but have very small amplitudes in the core, where almost all of the stellar mass resides. Although our stellar models are hydrostatic, the structure of their outer parts suggests that optically thick winds, driven by some combination of radiation pressure, transonic convection, and strange modes, are more likely than pulsation in the fundamental mode to limit the main-sequence lifetime.

Numerical exploration of non-axisymmetric divertor closure in the small angle slot (SAS) divertor at DIII-D

DOE PAGES

Frerichs, H.; Schmitz, O.; Covele, B.; ...

2018-02-28

Numerical simulations of toroidal asymmetries in a tightly baffled small angle slot (SAS) divertor on the DIII-D tokamak show that toroidal asymmetries in divertor closure result in (non-axisymmetric) local onset of detachment within a density window of 10-15% on top of the nominal threshold separatrix density. The SAS divertor is explored at DIII-D for improving access to cold, dissipative/detached divertor conditions. The narrow width of the slot divertor coupled with a small magnetic field line-to-target angle facilitates the buildup of neutral density, thereby increasing radiative and neutrals-related (atoms and molecules) losses in the divertor. Therefore, small changes in the strikemore » point location can be expected to have a large impact on diverter conditions. The combination of misaligned slot structure and non-axisymmetric perturbations to the magnetic field configuration causes the strike point to move along the divertor target plate, possibly leaving the diverter slot at some locations. The latter extreme case essentially introduces an opening in the divertor slot from where recycling neutrals can easily escape, and thereby degrade the performance of the slot divertor. Such a strike point dislocation is approximated by a finite gap in the divertor baffle for which three dimensional edge plasma and neutral gas simulations are performed with the EMC3-EIRENE code.« less

Numerical exploration of non-axisymmetric divertor closure in the small angle slot (SAS) divertor at DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frerichs, H.; Schmitz, O.; Covele, B.

Numerical simulations of toroidal asymmetries in a tightly baffled small angle slot (SAS) divertor on the DIII-D tokamak show that toroidal asymmetries in divertor closure result in (non-axisymmetric) local onset of detachment within a density window of 10-15% on top of the nominal threshold separatrix density. The SAS divertor is explored at DIII-D for improving access to cold, dissipative/detached divertor conditions. The narrow width of the slot divertor coupled with a small magnetic field line-to-target angle facilitates the buildup of neutral density, thereby increasing radiative and neutrals-related (atoms and molecules) losses in the divertor. Therefore, small changes in the strikemore » point location can be expected to have a large impact on diverter conditions. The combination of misaligned slot structure and non-axisymmetric perturbations to the magnetic field configuration causes the strike point to move along the divertor target plate, possibly leaving the diverter slot at some locations. The latter extreme case essentially introduces an opening in the divertor slot from where recycling neutrals can easily escape, and thereby degrade the performance of the slot divertor. Such a strike point dislocation is approximated by a finite gap in the divertor baffle for which three dimensional edge plasma and neutral gas simulations are performed with the EMC3-EIRENE code.« less

Numerical exploration of non-axisymmetric divertor closure in the small angle slot (SAS) divertor at DIII-D

NASA Astrophysics Data System (ADS)

Frerichs, H.; Schmitz, O.; Covele, B.; Feng, Y.; Guo, H. Y.; Hill, D.

2018-05-01

Numerical simulations of toroidal asymmetries in a tightly baffled small angle slot (SAS) divertor on the DIII-D tokamak show that toroidal asymmetries in divertor closure result in (non-axisymmetric) local onset of detachment within a density window of 10-15% on top of the nominal threshold separatrix density. The SAS divertor is explored at DIII-D for improving access to cold, dissipative/detached divertor conditions. The narrow width of the slot divertor coupled with a small magnetic field line-to-target angle facilitates the buildup of neutral density, thereby increasing radiative and neutrals-related (atoms and molecules) losses in the divertor. Small changes in the strike point location can be expected to have a large impact on divertor conditions. The combination of misaligned slot structure and non-axisymmetric perturbations to the magnetic field configuration causes the strike point to move along the divertor target plate, possibly leaving the divertor slot at some locations. The latter extreme case essentially introduces an opening in the divertor slot from where recycling neutrals can easily escape, and thereby degrade the performance of the slot divertor. Such a strike point dislocation is approximated by a finite gap in the divertor baffle for which 3D edge plasma and neutral gas simulations are performed with the EMC3-EIRENE code.

Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate

PubMed Central

Juul, Malene; Bertl, Johanna; Guo, Qianyun; Nielsen, Morten Muhlig; Świtnicki, Michał; Hornshøj, Henrik; Madsen, Tobias; Hobolth, Asger; Pedersen, Jakob Skou

2017-01-01

Non-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here, we develop a statistically founded non-coding driver-detection method, ncdDetect, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using ncdDetect, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n = 505), which top-ranked known drivers and identified new candidates. For individual candidates, presence of non-coding mutations associates with altered expression or decreased patient survival across an independent pan-cancer sample set (n = 5454). This includes an antigen-presenting gene (CD1A), where 5’UTR mutations correlate significantly with decreased survival in melanoma. Additionally, mutations in a base-excision-repair gene (SMUG1) correlate with a C-to-T mutational-signature. Overall, we find that a rich model of mutational heterogeneity facilitates non-coding driver identification and integrative analysis points to candidates of potential clinical relevance. DOI: http://dx.doi.org/10.7554/eLife.21778.001 PMID:28362259

Energy parasites trigger oncogene mutation.

PubMed

Pokorný, Jiří; Pokorný, Jan; Jandová, Anna; Kobilková, Jitka; Vrba, Jan; Vrba, Jan

2016-10-01

Cancer initialization can be explained as a result of parasitic virus energy consumption leading to randomized genome chemical bonding. Analysis of experimental data on cell-mediated immunity (CMI) containing about 12,000 cases of healthy humans, cancer patients and patients with precancerous cervical lesions disclosed that the specific cancer and the non-specific lactate dehydrogenase-elevating (LDH) virus antigen elicit similar responses. The specific antigen is effective only in cancer type of its origin but the non-specific antigen in all examined cancers. CMI results of CIN patients display both healthy and cancer state. The ribonucleic acid (RNA) of the LDH virus parasitizing on energy reduces the ratio of coherent/random oscillations. Decreased effect of coherent cellular electromagnetic field on bonding electrons in biological macromolecules leads to elevating probability of random genome reactions. Overlapping of wave functions in biological macromolecules depends on energy of the cellular electromagnetic field which supplies energy to bonding electrons for selective chemical bonds. CMI responses of cancer and LDH virus antigens in all examined healthy, precancerous and cancer cases point to energy mechanism in cancer initiation. Dependence of the rate of biochemical reactions on biological electromagnetic field explains yet unknown mechanism of genome mutation.

Genome-scale deletion screening of human long non-coding RNAs using a paired-guide RNA CRISPR library

PubMed Central

Zhu, Shiyou; Li, Wei; Liu, Jingze; Chen, Chen-Hao; Liao, Qi; Xu, Ping; Xu, Han; Xiao, Tengfei; Cao, Zhongzheng; Peng, Jingyu; Yuan, Pengfei; Brown, Myles; Liu, Xiaole Shirley; Wei, Wensheng

2017-01-01

CRISPR/Cas9 screens have been widely adopted to analyse coding gene functions, but high throughput screening of non-coding elements using this method is more challenging, because indels caused by a single cut in non-coding regions are unlikely to produce a functional knockout. A high-throughput method to produce deletions of non-coding DNA is needed. Herein, we report a high throughput genomic deletion strategy to screen for functional long non-coding RNAs (lncRNAs) that is based on a lentiviral paired-guide RNA (pgRNA) library. Applying our screening method, we identified 51 lncRNAs that can positively or negatively regulate human cancer cell growth. We individually validated 9 lncRNAs using CRISPR/Cas9-mediated genomic deletion and functional rescue, CRISPR activation or inhibition, and gene expression profiling. Our high-throughput pgRNA genome deletion method should enable rapid identification of functional mammalian non-coding elements. PMID:27798563

Role of non-coding RNAs in non-aging-related neurological disorders.

PubMed

Vieira, A S; Dogini, D B; Lopes-Cendes, I

2018-06-11

Protein coding sequences represent only 2% of the human genome. Recent advances have demonstrated that a significant portion of the genome is actively transcribed as non-coding RNA molecules. These non-coding RNAs are emerging as key players in the regulation of biological processes, and act as "fine-tuners" of gene expression. Neurological disorders are caused by a wide range of genetic mutations, epigenetic and environmental factors, and the exact pathophysiology of many of these conditions is still unknown. It is currently recognized that dysregulations in the expression of non-coding RNAs are present in many neurological disorders and may be relevant in the mechanisms leading to disease. In addition, circulating non-coding RNAs are emerging as potential biomarkers with great potential impact in clinical practice. In this review, we discuss mainly the role of microRNAs and long non-coding RNAs in several neurological disorders, such as epilepsy, Huntington disease, fragile X-associated ataxia, spinocerebellar ataxias, amyotrophic lateral sclerosis (ALS), and pain. In addition, we give information about the conditions where microRNAs have demonstrated to be potential biomarkers such as in epilepsy, pain, and ALS.

Genetics of Inflammatory Bowel Diseases

PubMed Central

McGovern, Dermot; Kugathasan, Subra; Cho, Judy H.

2015-01-01

In this Review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and non-coding genetic variation. In the small minority of loci where major association signals correspond to non-synonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that expression of the large majority of human genes is regulated by non-coding genetic variation. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (i.e. odds ratios markedly deviating from one) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in very-early onset, more severe cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility, through emerging precision medicine initiatives. We discuss the rapidly evolving area of direct to consumer genetic testing, as well as the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect of partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD. PMID:26255561

A finite element code for modelling tracer transport in a non-isothermal two-phase flow system for CO2 geological storage characterization

NASA Astrophysics Data System (ADS)

Tong, F.; Niemi, A. P.; Yang, Z.; Fagerlund, F.; Licha, T.; Sauter, M.

2011-12-01

This paper presents a new finite element method (FEM) code for modeling tracer transport in a non-isothermal two-phase flow system. The main intended application is simulation of the movement of so-called novel tracers for the purpose of characterization of geologically stored CO2 and its phase partitioning and migration in deep saline formations. The governing equations are based on the conservation of mass and energy. Among the phenomena accounted for are liquid-phase flow, gas flow, heat transport and the movement of the novel tracers. The movement of tracers includes diffusion and the advection associated with the gas and liquid flow. The temperature, gas pressure, suction, concentration of tracer in liquid phase and concentration of tracer in gas phase are chosen as the five primary variables. Parameters such as the density, viscosity, thermal expansion coefficient are expressed in terms of the primary variables. The governing equations are discretized in space using the Galerkin finite element formulation, and are discretized in time by one-dimensional finite difference scheme. This leads to an ill-conditioned FEM equation that has many small entries along the diagonal of the non-symmetric coefficient matrix. In order to deal with the problem of non-symmetric ill-conditioned matrix equation, special techniques are introduced . Firstly, only nonzero elements of the matrix need to be stored. Secondly, it is avoided to directly solve the whole large matrix. Thirdly, a strategy has been used to keep the diversity of solution methods in the calculation process. Additionally, an efficient adaptive mesh technique is included in the code in order to track the wetting front. The code has been validated against several classical analytical solutions, and will be applied for simulating the CO2 injection experiment to be carried out at the Heletz site, Israel, as part of the EU FP7 project MUSTANG.

An improved method for identification of small non-coding RNAs in bacteria using support vector machine

NASA Astrophysics Data System (ADS)

Barman, Ranjan Kumar; Mukhopadhyay, Anirban; Das, Santasabuj

2017-04-01

Bacterial small non-coding RNAs (sRNAs) are not translated into proteins, but act as functional RNAs. They are involved in diverse biological processes like virulence, stress response and quorum sensing. Several high-throughput techniques have enabled identification of sRNAs in bacteria, but experimental detection remains a challenge and grossly incomplete for most species. Thus, there is a need to develop computational tools to predict bacterial sRNAs. Here, we propose a computational method to identify sRNAs in bacteria using support vector machine (SVM) classifier. The primary sequence and secondary structure features of experimentally-validated sRNAs of Salmonella Typhimurium LT2 (SLT2) was used to build the optimal SVM model. We found that a tri-nucleotide composition feature of sRNAs achieved an accuracy of 88.35% for SLT2. We validated the SVM model also on the experimentally-detected sRNAs of E. coli and Salmonella Typhi. The proposed model had robustly attained an accuracy of 81.25% and 88.82% for E. coli K-12 and S. Typhi Ty2, respectively. We confirmed that this method significantly improved the identification of sRNAs in bacteria. Furthermore, we used a sliding window-based method and identified sRNAs from complete genomes of SLT2, S. Typhi Ty2 and E. coli K-12 with sensitivities of 89.09%, 83.33% and 67.39%, respectively.

The evolution and expression of the snaR family of small non-coding RNAs

PubMed Central

Parrott, Andrew M.; Tsai, Michael; Batchu, Priyanka; Ryan, Karen; Ozer, Harvey L.; Tian, Bin; Mathews, Michael B.

2011-01-01

We recently identified the snaR family of small non-coding RNAs that associate in vivo with the nuclear factor 90 (NF90/ILF3) protein. The major human species, snaR-A, is an RNA polymerase III transcript with restricted tissue distribution and orthologs in chimpanzee but not rhesus macaque or mouse. We report their expression in human tissues and their evolution in primates. snaR genes are exclusively in African Great Apes and some are unique to humans. Two novel families of snaR-related genetic elements were found in primates: CAS (catarrhine ancestor of snaR), limited to Old World Monkeys and apes; and ASR (Alu/snaR-related), present in all monkeys and apes. ASR and CAS appear to have spread by retrotransposition, whereas most snaR genes have spread by segmental duplication. snaR-A and snaR-G2 are differentially expressed in discrete regions of the human brain and other tissues, notably including testis. snaR-A is up-regulated in transformed and immortalized human cells, and is stably bound to ribosomes in HeLa cells. We infer that snaR evolved from the left monomer of the primate-specific Alu SINE family via ASR and CAS in conjunction with major primate speciation events, and suggest that snaRs participate in tissue- and species-specific regulation of cell growth and translation. PMID:20935053

High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

PubMed Central

de Castro Barbosa, Thais; Ingerslev, Lars R.; Alm, Petter S.; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M.; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R.; Barrès, Romain

2015-01-01

Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations. PMID:26977389

Transcriptome analysis of Bemisia tabaci during tomato yellow leaf curl virus acquisition and ribonucleic acid interference to manage whitefly-transmitted viruses

USDA-ARS?s Scientific Manuscript database

Over 300 viruses are transmitted by the whitefly, Bemisia tabaci, with 90% of them belonging to the genus, Begomovirus. Begomoviruses are obligately transmitted by whiteflies to a wide range of agriculture crops, resulting in billions of dollars lost annually, while jeopardizing food security worldw...

Use of novel RT-PCR assay to detect picobirnavirus in Poultry Intestinal samples collected from the field

USDA-ARS?s Scientific Manuscript database

Recent metagenomic analyses of the turkey gut ribonucleic acid (RNA) virus community in our laboratory have identified novel enteric RNA viruses that may play roles in the poultry enteric diseases and in performance problems noted in the field. This has lead to new molecular diagnostic assays for ce...

EPA Method 1615. Measurement of Enterovirus and Norovirus Occurrence in Water by Culture and RT-qPCR. Part III. Virus Detection by RT-qPCR

EPA Science Inventory

EPA Method 1615 measures enteroviruses and noroviruses present in environmental and drinking waters. The viral ribonucleic acid (RNA) from water sample concentrates is extracted and tested for enterovirus and norovirus RNA using reverse transcription-quantitative PCR (RT-qPCR). V...

Bringing RNA into View: RNA and Its Roles in Biology.

ERIC Educational Resources Information Center

Atkins, John F.; Ellington, Andrew; Friedman, B. Ellen; Gesteland, Raymond F.; Noller, Harry F.; Pasquale, Stephen M.; Storey, Richard D.; Uhlenbeck, Olke C.; Weiner, Alan M.

This guide presents a module for college students on ribonucleic acid (RNA) and its role in biology. The module aims to integrate the latest research and its findings into college-level biology and provide an opportunity for students to understand biological processes. Four activities are presented: (1) "RNA Structure: Tapes to Shapes"; (2) "RNA…

42 CFR 71.54 - Import regulations for infectious biological agents, infectious substances, and vectors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... segmented configuration and may be positive sense (same polarity as mRNA), negative sense, or ambisense... material. Deoxyribonucleic acid (DNA) or Ribonucleic acid (RNA) comprising the genome or organism's... threat to public health and safety as listed in 42 CFR 73.3 and 73.4. Vector. Any animals (vertebrate or...

42 CFR 71.54 - Import regulations for infectious biological agents, infectious substances, and vectors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... segmented configuration and may be positive sense (same polarity as mRNA), negative sense, or ambisense... material. Deoxyribonucleic acid (DNA) or Ribonucleic acid (RNA) comprising the genome or organism's... threat to public health and safety as listed in 42 CFR 73.3 and 73.4. Vector. Any animals (vertebrate or...

INVESTIGATION OF THE INFLUENCE OF THE POSITION INSIDE A SMALL AIRCRAFT ON THE COSMIC-RADIATION-INDUCED DOSE.

PubMed

Prado, A C M; Pazianotto, M T; Gonçalez, O L; Dos Santos, L R; Caldeira, A D; Pereira, H H C; Hubert, G; Federico, C A

2017-11-01

This article report the measurements on-board a small aircraft at the same altitude and around the same geographic coordinates. The measurements of Ambient Dose Equivalent Rate (H*(10)) were performed in several positions inside the aircraft, close and far from the pilot location and the discrimination between neutron and non-neutron components. The results show that the neutrons are attenuated close to fuel depots and the non-neutron component appears to have the opposite behavior inside the aircraft. These experimental results are also confronted with results from Monte Carlo simulation, obtained with the MCNPX code, using a simplified model of the Learjet-type aircraft and a modeling of the standard atmosphere, which reproduces the real energy and angular distribution of the particles. The Monte Carlo simulation agreed with the experimental measurements and shows that the total H*(10) presents small variation (around 1%) between the positions inside aircraft, although the neutron spectra present significant variations. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Roles of Non-Coding RNA in Sugarcane-Microbe Interaction.

PubMed

Thiebaut, Flávia; Rojas, Cristian A; Grativol, Clícia; Calixto, Edmundo P da R; Motta, Mariana R; Ballesteros, Helkin G F; Peixoto, Barbara; de Lima, Berenice N S; Vieira, Lucas M; Walter, Maria Emilia; de Armas, Elvismary M; Entenza, Júlio O P; Lifschitz, Sergio; Farinelli, Laurent; Hemerly, Adriana S; Ferreira, Paulo C G

2017-12-20

Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae . Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs) were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a copper-transporter gene whose expression was induced in the presence of A. avenae , while the siRNAs were repressed in the presence of A. avenae . Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408-a copper-microRNA-was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 5'RACE (rapid amplification of cDNA ends) assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly.

Roles of Non-Coding RNA in Sugarcane-Microbe Interaction

PubMed Central

Grativol, Clícia; Motta, Mariana R.; Ballesteros, Helkin G. F.; Peixoto, Barbara; Vieira, Lucas M.; Walter, Maria Emilia; de Armas, Elvismary M.; Entenza, Júlio O. P.; Lifschitz, Sergio; Farinelli, Laurent; Hemerly, Adriana S.

2017-01-01

Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae. Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs) were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a copper-transporter gene whose expression was induced in the presence of A. avenae, while the siRNAs were repressed in the presence of A. avenae. Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408—a copper-microRNA—was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 5′RACE (rapid amplification of cDNA ends) assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly. PMID:29657296

Small RNA populations revealed by blocking rRNA fragments in Drosophila melanogaster reproductive tissues

PubMed Central

Dalmay, Tamas

2018-01-01

RNA interference (RNAi) is a complex and highly conserved regulatory mechanism mediated via small RNAs (sRNAs). Recent technical advances in high throughput sequencing have enabled an increasingly detailed analysis of sRNA abundances and profiles in specific body parts and tissues. This enables investigations of the localized roles of microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, variation in the proportions of non-coding RNAs in the samples being compared can hinder these analyses. Specific tissues may vary significantly in the proportions of fragments of longer non-coding RNAs (such as ribosomal RNA or transfer RNA) present, potentially reflecting tissue-specific differences in biological functions. For example, in Drosophila, some tissues contain a highly abundant 30nt rRNA fragment (the 2S rRNA) as well as abundant 5’ and 3’ terminal rRNA fragments. These can pose difficulties for the construction of sRNA libraries as they can swamp the sequencing space and obscure sRNA abundances. Here we addressed this problem and present a modified “rRNA blocking” protocol for the construction of high-definition (HD) adapter sRNA libraries, in D. melanogaster reproductive tissues. The results showed that 2S rRNAs targeted by blocking oligos were reduced from >80% to < 0.01% total reads. In addition, the use of multiple rRNA blocking oligos to bind the most abundant rRNA fragments allowed us to reveal the underlying sRNA populations at increased resolution. Side-by-side comparisons of sequencing libraries of blocked and non-blocked samples revealed that rRNA blocking did not change the miRNA populations present, but instead enhanced their abundances. We suggest that this rRNA blocking procedure offers the potential to improve the in-depth analysis of differentially expressed sRNAs within and across different tissues. PMID:29474379

[DNA prints instead of plantar prints in neonatal identification].

PubMed

Rodríguez-Alarcón Gómez, J; Martińez de Pancorbo Gómez, M; Santillana Ferrer, L; Castro Espido, A; Melchor Maros, J C; Linares Uribe, M A; Fernández-Llebrez del Rey, L; Aranguren Dúo, G

1996-06-22

To check the possible usefulness in studying DNA in dried blood spots taken on filter paper blotters for newborn identification. It set out to establish: 1. The validity of the method for analysis; 2. The validity of all stored samples (such as those kept in clinical records); 3. Guarantee of non-intrusion in the genetic code; 4. Acceptable price and execution time. Forty (40) anonymous 13-year-old samples of 20 subjects (2 per subject) were studied. DNA was extracted using Chelex resin and the STR ("small tandem repeat") of microsatellite DNA was studies using the "polimerase chain reaction method" (PCR). Three non coding DNA loci (CSF1PO, TPOX and THO1) were analyzed by Multiplex amplification. It was possible to type 39 samples, making it possible to match the 20 cases (one by exclusion). The complete procedure yielded the results within 24 hours in all cases. The estimated final cost was found to be a fifth of that conventional maternity/paternity tests. The study carried out made matching possible in all 20 cases (directly in 19 cases). It was not necessary to study DNA coding areas. The validity of the method for analyzing samples stored for 13 years without any special care was also demonstrated. The technic was fast, producing the results within 24 hours, and at reasonable cost.

A simple model for molecular hydrogen chemistry coupled to radiation hydrodynamics

NASA Astrophysics Data System (ADS)

Nickerson, Sarah; Teyssier, Romain; Rosdahl, Joakim

2018-06-01

We introduce non-equilibrium molecular hydrogen chemistry into the radiation-hydrodynamics code RAMSES-RT. This is an adaptive mesh refinement grid code with radiation hydrodynamics that couples the thermal chemistry of hydrogen and helium to moment-based radiative transfer with the Eddington tensor closure model. The H2 physics that we include are formation on dust grains, gas phase formation, formation by three-body collisions, collisional destruction, photodissociation, photoionisation, cosmic ray ionisation and self-shielding. In particular, we implement the first model for H2 self-shielding that is tied locally to moment-based radiative transfer by enhancing photo-destruction. This self-shielding from Lyman-Werner line overlap is critical to H2 formation and gas cooling. We can now track the non-equilibrium evolution of molecular, atomic, and ionised hydrogen species with their corresponding dissociating and ionising photon groups. Over a series of tests we show that our model works well compared to specialised photodissociation region codes. We successfully reproduce the transition depth between molecular and atomic hydrogen, molecular cooling of the gas, and a realistic Strömgren sphere embedded in a molecular medium. In this paper we focus on test cases to demonstrate the validity of our model on small scales. Our ultimate goal is to implement this in large-scale galactic simulations.

Parallel evolution of chordate cis-regulatory code for development.

PubMed

Doglio, Laura; Goode, Debbie K; Pelleri, Maria C; Pauls, Stefan; Frabetti, Flavia; Shimeld, Sebastian M; Vavouri, Tanya; Elgar, Greg

2013-11-01

Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs), yet these elements have not been identified in urochordate genomes. Consequently the evolution of the cis-regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs) are associated with largely the same key regulatory genes as vertebrate CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene expression in both zebrafish and Ciona embryos, in a pattern that at least partially overlaps that of the gene they associate with, despite the absence of sequence identity. We also show that the ability of a ciCNE to up-regulate gene expression in vertebrate embryos can in some cases be localised to short sub-sequences, suggesting that functional cross-talk may be defined by small regions of ancestral regulatory logic, although functional sub-sequences may also be dispersed across the whole element. We conclude that the structure and organisation of cis-regulatory modules is very different between vertebrates and urochordates, reflecting their separate evolutionary histories. However, functional cross-talk still exists because the same repertoire of transcription factors has likely guided their parallel evolution, exploiting similar sets of binding sites but in different combinations.

Spatial coding of object typical size: evidence for a SNARC-like effect.

PubMed

Sellaro, Roberta; Treccani, Barbara; Job, Remo; Cubelli, Roberto

2015-11-01

The present study aimed to assess whether the representation of the typical size of objects can interact with response position codes in two-choice bimanual tasks, and give rise to a SNARC-like effect (faster responses when the representation of the typical size of the object to which the target stimulus refers corresponds to response side). Participants performed either a magnitude comparison task (in which they were required to judge whether the target was smaller or larger than a reference stimulus; Experiment 1) or a semantic decision task (in which they had to classify the target as belonging to either the category of living or non-living entities; Experiment 2). Target stimuli were pictures or written words referring to either typically large and small animals or inanimate objects. In both tasks, participants responded by pressing a left- or right-side button. Results showed that, regardless of the to-be-performed task (magnitude comparison or semantic decision) and stimulus format (picture or word), left responses were faster when the target represented typically small-sized entities, whereas right responses were faster for typically large-sized entities. These results provide evidence that the information about the typical size of objects is activated even if it is not requested by the task, and are consistent with the idea that objects' typical size is automatically spatially coded, as has been proposed to occur for number magnitudes. In this representation, small objects would be on the left and large objects would be on the right. Alternative interpretations of these results are also discussed.

Regulation of mammalian cell differentiation by long non-coding RNAs

PubMed Central

Hu, Wenqian; Alvarez-Dominguez, Juan R; Lodish, Harvey F

2012-01-01

Differentiation of specialized cell types from stem and progenitor cells is tightly regulated at several levels, both during development and during somatic tissue homeostasis. Many long non-coding RNAs have been recognized as an additional layer of regulation in the specification of cellular identities; these non-coding species can modulate gene-expression programmes in various biological contexts through diverse mechanisms at the transcriptional, translational or messenger RNA stability levels. Here, we summarize findings that implicate long non-coding RNAs in the control of mammalian cell differentiation. We focus on several representative differentiation systems and discuss how specific long non-coding RNAs contribute to the regulation of mammalian development. PMID:23070366

75 FR 13802 - Small Business Size Standards: Waiver of the Nonmanufacturer Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

...) code 325120 (Industrial Gases Manufacturing). According to the request, no small business manufacturers... for LPG, PSC 6830 (Compressed and Liquefied Gases), under NAICS code 325120 (Industrial Gases... for Liquid Propane Gas (LPG). SUMMARY: The U.S. Small Business Administration (SBA) is considering...

Dual stator winding variable speed asynchronous generator: optimal design and experiments

NASA Astrophysics Data System (ADS)

Tutelea, L. N.; Deaconu, S. I.; Popa, G. N.

2015-06-01

In the present paper is carried out a theoretical and experimental study of dual stator winding squirrel cage asynchronous generator (DSWA) behavior in the presence of saturation regime (non-sinusoidal) due to the variable speed operation. The main aims are the determination of the relations of calculating the equivalent parameters of the machine windings to optimal design using a Matlab code. Issue is limited to three phase range of double stator winding cage-induction generator of small sized powers, the most currently used in the small adjustable speed wind or hydro power plants. The tests were carried out using three-phase asynchronous generator having rated power of 6 [kVA].

Low-molecular-weight (4.5S) ribonucleic acid in higher-plant chloroplast ribosomes.

PubMed Central

Whitfeld, P R; Leaver, C J; Bottomley, W; Atchison, B

1978-01-01

A species of RNA that migrates on 10% (w/v) polyacrylamide gels between 5S and 4S RNA was detected in spinach chloroplasts. This RNA (referred to as 4.5 S RNA) was present in amounts equimolar to the 5S RNA and its molecular weight was estimated to be approx. 33 000. Fractionation of the chloroplast components showed that the 4.5S RNA was associated with the 50 S ribosomal subunit and that it could be removed by washing the ribosomes with a buffer containing 0.01 M-EDTA and 0.5 M-KCl. It did not appear to be a cleavage product of the labile 23 S RNA of spinach chloroplast ribosomes. When 125I-labelled 4.5 S RNA was hybridized to fragments of spinach chloroplast DNA produced by SmaI restriction endonuclease, a single fragment (mol.wt. 1.15 times 10(6)) became labelled. The same DNA fragment also hybridized to chloroplast 5 S RNA and part of the 23 S RNA. It was concluded that the coding sequence for 4.5 S RNA was part of, or immediately adjacent to, the rRNA-gene region in chloroplast DNA . A comparable RNA species was observed in chloroplasts of tobacco and pea leaves. Images Fig. 8. PMID:743229

Monte Carlo modelling the dosimetric effects of electrode material on diamond detectors.

PubMed

Baluti, Florentina; Deloar, Hossain M; Lansley, Stuart P; Meyer, Juergen

2015-03-01

Diamond detectors for radiation dosimetry were modelled using the EGSnrc Monte Carlo code to investigate the influence of electrode material and detector orientation on the absorbed dose. The small dimensions of the electrode/diamond/electrode detector structure required very thin voxels and the use of non-standard DOSXYZnrc Monte Carlo model parameters. The interface phenomena was investigated by simulating a 6 MV beam and detectors with different electrode materials, namely Al, Ag, Cu and Au, with thickens of 0.1 µm for the electrodes and 0.1 mm for the diamond, in both perpendicular and parallel detector orientation with regards to the incident beam. The smallest perturbations were observed for the parallel detector orientation and Al electrodes (Z = 13). In summary, EGSnrc Monte Carlo code is well suited for modelling small detector geometries. The Monte Carlo model developed is a useful tool to investigate the dosimetric effects caused by different electrode materials. To minimise perturbations cause by the detector electrodes, it is recommended that the electrodes should be made from a low-atomic number material and placed parallel to the beam direction.

Comparative Evaluation of Different Optimization Algorithms for Structural Design Applications

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Coroneos, Rula M.; Guptill, James D.; Hopkins, Dale A.

1996-01-01

Non-linear programming algorithms play an important role in structural design optimization. Fortunately, several algorithms with computer codes are available. At NASA Lewis Research Centre, a project was initiated to assess the performance of eight different optimizers through the development of a computer code CometBoards. This paper summarizes the conclusions of that research. CometBoards was employed to solve sets of small, medium and large structural problems, using the eight different optimizers on a Cray-YMP8E/8128 computer. The reliability and efficiency of the optimizers were determined from the performance of these problems. For small problems, the performance of most of the optimizers could be considered adequate. For large problems, however, three optimizers (two sequential quadratic programming routines, DNCONG of IMSL and SQP of IDESIGN, along with Sequential Unconstrained Minimizations Technique SUMT) outperformed others. At optimum, most optimizers captured an identical number of active displacement and frequency constraints but the number of active stress constraints differed among the optimizers. This discrepancy can be attributed to singularity conditions in the optimization and the alleviation of this discrepancy can improve the efficiency of optimizers.

RNA Relics and Origin of Life

PubMed Central

Demongeot, Jacques; Glade, Nicolas; Moreira, Andrés; Vial, Laurent

2009-01-01

A number of small RNA sequences, located in different non-coding sequences and highly preserved across the tree of life, have been suggested to be molecular fossils, of ancient (and possibly primordial) origin. On the other hand, recent years have revealed the existence of ubiquitous roles for small RNA sequences in modern organisms, in functions ranging from cell regulation to antiviral activity. We propose that a single thread can be followed from the beginning of life in RNA structures selected only for stability reasons through the RNA relics and up to the current coevolution of RNA sequences; such an understanding would shed light both on the history and on the present development of the RNA machinery and interactions. After presenting the evidence (by comparing their sequences) that points toward a common thread, we discuss a scenario of genome coevolution (with emphasis on viral infectious processes) and finally propose a plan for the reevaluation of the stereochemical theory of the genetic code; we claim that it may still be relevant, and not only for understanding the origin of life, but also for a comprehensive picture of regulation in present-day cells. PMID:20111682

RISC assembly: Coordination between small RNAs and Argonaute proteins.

PubMed

Kobayashi, Hotaka; Tomari, Yukihide

2016-01-01

Non-coding RNAs generally form ribonucleoprotein (RNP) complexes with their partner proteins to exert their functions. Small RNAs, including microRNAs, small interfering RNAs, and PIWI-interacting RNAs, assemble with Argonaute (Ago) family proteins into the effector complex called RNA-induced silencing complex (RISC), which mediates sequence-specific target gene silencing. RISC assembly is not a simple binding between a small RNA and Ago; rather, it follows an ordered multi-step pathway that requires specific accessory factors. Some steps of RISC assembly and RISC-mediated gene silencing are dependent on or facilitated by particular intracellular platforms, suggesting their spatial regulation. In this review, we summarize the currently known mechanisms for RISC assembly of each small RNA class and propose a revised model for the role of the chaperone machinery in the duplex-initiated RISC assembly pathway. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

BRD4 assists elongation of both coding and enhancer RNAs guided by histone acetylation

PubMed Central

Kanno, Tomohiko; Kanno, Yuka; LeRoy, Gary; Campos, Eric; Sun, Hong-Wei; Brooks, Stephen R; Vahedi, Golnaz; Heightman, Tom D; Garcia, Benjamin A; Reinberg, Danny; Siebenlist, Ulrich; O’Shea, John J; Ozato, Keiko

2016-01-01

Small-molecule BET inhibitors interfere with the epigenetic interactions between acetylated histones and the bromodomains of the BET family proteins, including BRD4, and they potently inhibit growth of malignant cells by targeting cancer-promoting genes. BRD4 interacts with the pause-release factor P-TEFb, and has been proposed to release Pol II from promoter-proximal pausing. We show that BRD4 occupied widespread genomic regions in mouse cells, and directly stimulated elongation of both protein-coding transcripts and non-coding enhancer RNAs (eRNAs), dependent on the function of bromodomains. BRD4 interacted physically with elongating Pol II complexes, and assisted Pol II progression through hyper-acetylated nucleosomes by interacting with acetylated histones via bromodomains. On active enhancers, the BET inhibitor JQ1 antagonized BRD4-associated eRNA synthesis. Thus, BRD4 is involved in multiple steps of the transcription hierarchy, primarily by assisting transcript elongation both at enhancers and on gene bodies. PMID:25383670

Advanced GF(3²) nonbinary LDPC coded modulation with non-uniform 9-QAM outperforming star 8-QAM.

PubMed

Liu, Tao; Lin, Changyu; Djordjevic, Ivan B

2016-06-27

In this paper, we first describe a 9-symbol non-uniform signaling scheme based on Huffman code, in which different symbols are transmitted with different probabilities. By using the Huffman procedure, prefix code is designed to approach the optimal performance. Then, we introduce an algorithm to determine the optimal signal constellation sets for our proposed non-uniform scheme with the criterion of maximizing constellation figure of merit (CFM). The proposed nonuniform polarization multiplexed signaling 9-QAM scheme has the same spectral efficiency as the conventional 8-QAM. Additionally, we propose a specially designed GF(3²) nonbinary quasi-cyclic LDPC code for the coded modulation system based on the 9-QAM non-uniform scheme. Further, we study the efficiency of our proposed non-uniform 9-QAM, combined with nonbinary LDPC coding, and demonstrate by Monte Carlo simulation that the proposed GF(2³) nonbinary LDPC coded 9-QAM scheme outperforms nonbinary LDPC coded uniform 8-QAM by at least 0.8dB.

A new method for species identification via protein-coding and non-coding DNA barcodes by combining machine learning with bioinformatic methods.

PubMed

Zhang, Ai-bing; Feng, Jie; Ward, Robert D; Wan, Ping; Gao, Qiang; Wu, Jun; Zhao, Wei-zhong

2012-01-01

Species identification via DNA barcodes is contributing greatly to current bioinventory efforts. The initial, and widely accepted, proposal was to use the protein-coding cytochrome c oxidase subunit I (COI) region as the standard barcode for animals, but recently non-coding internal transcribed spacer (ITS) genes have been proposed as candidate barcodes for both animals and plants. However, achieving a robust alignment for non-coding regions can be problematic. Here we propose two new methods (DV-RBF and FJ-RBF) to address this issue for species assignment by both coding and non-coding sequences that take advantage of the power of machine learning and bioinformatics. We demonstrate the value of the new methods with four empirical datasets, two representing typical protein-coding COI barcode datasets (neotropical bats and marine fish) and two representing non-coding ITS barcodes (rust fungi and brown algae). Using two random sub-sampling approaches, we demonstrate that the new methods significantly outperformed existing Neighbor-joining (NJ) and Maximum likelihood (ML) methods for both coding and non-coding barcodes when there was complete species coverage in the reference dataset. The new methods also out-performed NJ and ML methods for non-coding sequences in circumstances of potentially incomplete species coverage, although then the NJ and ML methods performed slightly better than the new methods for protein-coding barcodes. A 100% success rate of species identification was achieved with the two new methods for 4,122 bat queries and 5,134 fish queries using COI barcodes, with 95% confidence intervals (CI) of 99.75-100%. The new methods also obtained a 96.29% success rate (95%CI: 91.62-98.40%) for 484 rust fungi queries and a 98.50% success rate (95%CI: 96.60-99.37%) for 1094 brown algae queries, both using ITS barcodes.

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Hongxue; Department of Urology, Hospital of Xinjiang Production and Construction Corps, Urumqi 830002; Li, Xuechao

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cellmore » apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.« less

Efficient hybrid-symbolic methods for quantum mechanical calculations

NASA Astrophysics Data System (ADS)

Scott, T. C.; Zhang, Wenxing

2015-06-01

We present hybrid symbolic-numerical tools to generate optimized numerical code for rapid prototyping and fast numerical computation starting from a computer algebra system (CAS) and tailored to any given quantum mechanical problem. Although a major focus concerns the quantum chemistry methods of H. Nakatsuji which has yielded successful and very accurate eigensolutions for small atoms and molecules, the tools are general and may be applied to any basis set calculation with a variational principle applied to its linear and non-linear parameters.

Theoretical Investigation Leading to Energy Storage in Atomic and Molecular Systems

DTIC Science & Technology

1990-12-01

can be calculated in a single run. 21 j) Non-gradient optimization of basis function exponents is possible. The source code can be modified to carry...basis. The 10s3p/5s3p basis consists of the 9s/4s contraction of Siegbahn and Liu (Reference 91) augmented by a diffuse s-type function ( exponent ...vibrational modes. Introduction of diffuse basis functions and optimization of the d-orbital exponents have a small but important effect on the

Epigenetic Therapy in Lung Cancer - Role of microRNAs.

PubMed

Rothschild, Sacha I

2013-01-01

Lung cancer is the leading cause of cancer deaths worldwide. microRNAs (miRNAs) are a class of small non-coding RNA species that have been implicated in the control of many fundamental cellular and physiological processes such as cellular differentiation, proliferation, apoptosis, and stem cell maintenance. Some miRNAs have been categorized as "oncomiRs" as opposed to "tumor suppressor miRs." This review focuses on the role of miRNAs in the lung cancer carcinogenesis and their potential as diagnostic, prognostic, or predictive markers.

Identification of MicroRNAs in the Coral Stylophora pistillata

PubMed Central

Liew, Yi Jin; Aranda, Manuel; Carr, Adrian; Baumgarten, Sebastian; Zoccola, Didier; Tambutté, Sylvie; Allemand, Denis; Micklem, Gos; Voolstra, Christian R.

2014-01-01

Coral reefs are major contributors to marine biodiversity. However, they are in rapid decline due to global environmental changes such as rising sea surface temperatures, ocean acidification, and pollution. Genomic and transcriptomic analyses have broadened our understanding of coral biology, but a study of the microRNA (miRNA) repertoire of corals is missing. miRNAs constitute a class of small non-coding RNAs of ∼22 nt in size that play crucial roles in development, metabolism, and stress response in plants and animals alike. In this study, we examined the coral Stylophora pistillata for the presence of miRNAs and the corresponding core protein machinery required for their processing and function. Based on small RNA sequencing, we present evidence for 31 bona fide microRNAs, 5 of which (miR-100, miR-2022, miR-2023, miR-2030, and miR-2036) are conserved in other metazoans. Homologues of Argonaute, Piwi, Dicer, Drosha, Pasha, and HEN1 were identified in the transcriptome of S. pistillata based on strong sequence conservation with known RNAi proteins, with additional support derived from phylogenetic trees. Examination of putative miRNA gene targets indicates potential roles in development, metabolism, immunity, and biomineralisation for several of the microRNAs. Here, we present first evidence of a functional RNAi machinery and five conserved miRNAs in S. pistillata, implying that miRNAs play a role in organismal biology of scleractinian corals. Analysis of predicted miRNA target genes in S. pistillata suggests potential roles of miRNAs in symbiosis and coral calcification. Given the importance of miRNAs in regulating gene expression in other metazoans, further expression analyses of small non-coding RNAs in transcriptional studies of corals should be informative about miRNA-affected processes and pathways. PMID:24658574

Argonaute: The executor of small RNA function.

PubMed

Azlan, Azali; Dzaki, Najat; Azzam, Ghows

2016-08-20

The discovery of small non-coding RNAs - microRNA (miRNA), short interfering RNA (siRNA) and PIWI-interacting RNA (piRNA) - represents one of the most exciting frontiers in biology specifically on the mechanism of gene regulation. In order to execute their functions, these small RNAs require physical interactions with their protein partners, the Argonaute (AGO) family proteins. Over the years, numerous studies have made tremendous progress on understanding the roles of AGO in gene silencing in various organisms. In this review, we summarize recent progress of AGO-mediated gene silencing and other cellular processes in which AGO proteins have been implicated with a particular focus on progress made in flies, humans and other model organisms as compliment. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Computational Approaches to Nucleic Acid Origami.

PubMed

Jabbari, Hosna; Aminpour, Maral; Montemagno, Carlo

2015-10-12

Recent advances in experimental DNA origami have dramatically expanded the horizon of DNA nanotechnology. Complex 3D suprastructures have been designed and developed using DNA origami with applications in biomaterial science, nanomedicine, nanorobotics, and molecular computation. Ribonucleic acid (RNA) origami has recently been realized as a new approach. Similar to DNA, RNA molecules can be designed to form complex 3D structures through complementary base pairings. RNA origami structures are, however, more compact and more thermodynamically stable due to RNA's non-canonical base pairing and tertiary interactions. With all these advantages, the development of RNA origami lags behind DNA origami by a large gap. Furthermore, although computational methods have proven to be effective in designing DNA and RNA origami structures and in their evaluation, advances in computational nucleic acid origami is even more limited. In this paper, we review major milestones in experimental and computational DNA and RNA origami and present current challenges in these fields. We believe collaboration between experimental nanotechnologists and computer scientists are critical for advancing these new research paradigms.

A narrowband CDMA communications payload for little LEOS applications

NASA Astrophysics Data System (ADS)

Michalik, H.; Hävecker, W.; Ginati, A.

1996-09-01

In recent years Code Division Multiple Access (CDMA) techniques have been investigated for application in Local Area Networks [J. A. Salehi, IEEE Trans. Commun. 37 (1989)]as well as in Mobile Communications [R. Kohno et al., IEEE Commun. Mag. Jan (1995)]. The main attraction of these techniques is due to potential higher throughput and capacity of such systems under certain conditions compared to conventional multi-access schemes like frequency and time division multiplexing. Mobile communication over a Satellite Link represents in some terms the "worst case" for operating a CDMA-system. Considering e.g. the uplink case from mobile to satellite, the imperfections due to different and time varying channel conditions will add to the well known effects of Multiple Access Interference (MAI) between the simultaneously active users at the satellite receiver. In addition, bandwidth constraints due to the non-availability of large bandwidth channels in the interesting frequency bands, exist for small systems. As a result, for a given service in terms of user data rates, the practical code sequence lengths are limited as well as the available number of codes within a code set. In this paper a communications payload for Small Satellite Applications with CDMA uplink and C/TDMA downlink under the constraint of bandwidth limitations is proposed. To optimise the performance under the above addressed imperfections the system provides ability for power control and synchronisation for the CDMA uplink. The major objectives of this project are studying, development and testing of such a system for educational purposes and technology development at Hochschule Bremen.

A duplex real-time RT-PCR system with an internal control offers sensitive and reliable broad spectrum detection of Squash mosaic virus variants

USDA-ARS?s Scientific Manuscript database

Squash mosaic virus (SqMV) is a seed-borne virus, belonging to the genus Commovirus in the subfamily Comoviridae of family Secoviridae. SqMV has a bipartite single-stranded ribonucleic acid (RNA) genome (RNA1 and RNA2) encapsidated separately with two capsid proteins. Two serotypes (genotypes) of ...

Comparative transcriptome analysis in Bemisia tabaci in response to tomato yellow leaf curl virus and development of ribonucleic acid interference to manage whitefly-transmitted viruses

USDA-ARS?s Scientific Manuscript database

The whitefly, Bemisia tabaci transmits over 300 plant viruses, with the majority of them belonging to the Begomovirus genus. Begomoviruses are obligately transmitted to a wide range of agriculture crops, resulting in the loss of billions of dollars annually, while jeopardizing food security worldwid...

Future Technology Themes: 2030 to 2060

DTIC Science & Technology

2013-07-01

Rocket-Based Combined Cycle RF Radio Frequency RNA Ribonucleic Acid SA Situational Awareness SEAD Suppression of Enemy Air Defences SME...and re-routing light in information processing and optical communications ; or for processing radio signals in mobile phones [44]. UNCLASSIFIED DSTO...make use of network polymorphism technologies from 2020 onwards to create frequency -agile and adaptive14 communications links that would change network

EFFECT OF ULTRA-VIOLET IRRADIATION OF RIBONUCLEIC ACID ON ITS CHROMATOGRAPHIC BEHAVIOUR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubinski, H.

1963-11-01

Experiments were made to illustrate the effects of ultraviolet radiation on RNA isolated from uninfected mammalian cells as well as those from those infected with polio virus. The chromatographic recovery of irradiated RNA, as judged by ultraviolet adsorbance and radioactivity (no plaque formers were found after irradiation), was considerably lower than that of unirradiated RNA. (P.C.H.)

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction

PubMed Central

Mellert, Hestia S.; Alexander, Kristin E.; Jackson, Leisa P.; Pestano, Gary A.

2018-01-01

We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR). Samples are evaluated for both the target biomarker as well as a control gene. Test validation included limit of detection, accuracy, and robustness studies with analytic samples. The method developed as a result of these studies reproducibly detect multiple fusion variants for ROS1 (C-Ros proto-oncogene 1; 8 variants) and RET (rearranged during transfection proto-oncogene; 8 variants). The sample processing workflow has been optimized so that test results can consistently be generated within 72 hours of sample receipt. PMID:29683453

RoboOligo: software for mass spectrometry data to support manual and de novo sequencing of post-transcriptionally modified ribonucleic acids

PubMed Central

Sample, Paul J.; Gaston, Kirk W.; Alfonzo, Juan D.; Limbach, Patrick A.

2015-01-01

Ribosomal ribonucleic acid (RNA), transfer RNA and other biological or synthetic RNA polymers can contain nucleotides that have been modified by the addition of chemical groups. Traditional Sanger sequencing methods cannot establish the chemical nature and sequence of these modified-nucleotide containing oligomers. Mass spectrometry (MS) has become the conventional approach for determining the nucleotide composition, modification status and sequence of modified RNAs. Modified RNAs are analyzed by MS using collision-induced dissociation tandem mass spectrometry (CID MS/MS), which produces a complex dataset of oligomeric fragments that must be interpreted to identify and place modified nucleosides within the RNA sequence. Here we report the development of RoboOligo, an interactive software program for the robust analysis of data generated by CID MS/MS of RNA oligomers. There are three main functions of RoboOligo: (i) automated de novo sequencing via the local search paradigm. (ii) Manual sequencing with real-time spectrum labeling and cumulative intensity scoring. (iii) A hybrid approach, coined ‘variable sequencing’, which combines the user intuition of manual sequencing with the high-throughput sampling of automated de novo sequencing. PMID:25820423

Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects.

PubMed

Nakamura, Tsutomu; Sakaeda, Toshiyuki; Horinouchi, Masanori; Tamura, Takao; Aoyama, Nobuo; Shirakawa, Toshiro; Matsuo, Masafumi; Kasuga, Masato; Okumura, Katsuhiko

2002-04-01

The effect of the C3435T mutation at exon 26 of the MDR1 gene on the expression levels of MDR1 messenger ribonucleic acid (mRNA) was evaluated by means of real-time polymerase chain reaction in 51 biopsy specimens of duodenum obtained from 13 healthy Japanese subjects. The mRNA levels of MDR1 were 0.38 +/- 0.15, 0.56 +/- 0.14, and 1.13 +/- 0.42 (mean value +/- SE) in the subjects with the homozygote of wild-type allele (C/C), compound heterozygote with mutant T allele (C/T), and the homozygote of the mutant allele (T/T), respectively, reasonably explaining the lower digoxin serum concentration after administration of a single oral dose to subjects harboring a mutant T allele. Good correlation (r =.797; P <.01) was observed between the mRNA concentrations of MDR1 and CYP3A4 in the individual biopsy specimens. This finding suggested a lower plasma concentration of the substrates for CYP3A4 in subjects harboring the C3435T mutation of the MDR1 gene.

Tailored Codes for Small Quantum Memories

NASA Astrophysics Data System (ADS)

Robertson, Alan; Granade, Christopher; Bartlett, Stephen D.; Flammia, Steven T.

2017-12-01

We demonstrate that small quantum memories, realized via quantum error correction in multiqubit devices, can benefit substantially by choosing a quantum code that is tailored to the relevant error model of the system. For a biased noise model, with independent bit and phase flips occurring at different rates, we show that a single code greatly outperforms the well-studied Steane code across the full range of parameters of the noise model, including for unbiased noise. In fact, this tailored code performs almost optimally when compared with 10 000 randomly selected stabilizer codes of comparable experimental complexity. Tailored codes can even outperform the Steane code with realistic experimental noise, and without any increase in the experimental complexity, as we demonstrate by comparison in the observed error model in a recent seven-qubit trapped ion experiment.

Director of Small and Disadvantaged Business Utilization

DTIC Science & Technology

1989-03-17

Small and Disadvantaged Business Utilization References: (a) Title 15, United States Code (b) Title 10, United States Code (c) DoD 5025.1-M, "Department...position of Director of Small and Disadvantaged Business Utilization (Director, SADBU) under the direction, authority, and control of the Under...Defense Agencies, and the DoD Field Activities. C. RESPONSIBILITIES The Director of Small and Disadvantaged Business Utilization shall serve as the

The developmental transcriptome of Drosophila melanogaster

DOE Office of Scientific and Technical Information (OSTI.GOV)

University of Connecticut; Graveley, Brenton R.; Brooks, Angela N.

Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, predictionmore » and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development. Drosophila melanogaster is an important non-mammalian model system that has had a critical role in basic biological discoveries, such as identifying chromosomes as the carriers of genetic information and uncovering the role of genes in development. Because it shares a substantial genic content with humans, Drosophila is increasingly used as a translational model for human development, homeostasis and disease. High-quality maps are needed for all functional genomic elements. Previous studies demonstrated that a rich collection of genes is deployed during the life cycle of the fly. Although expression profiling using microarrays has revealed the expression of, 13,000 annotated genes, it is difficult to map splice junctions and individual base modifications generated by RNA editing using such approaches. Single-base resolution is essential to define precisely the elements that comprise the Drosophila transcriptome. Estimates of the number of transcript isoforms are less accurate than estimates of the number of genes. Whereas, 20% of Drosophila genes are annotated as encoding alternatively spliced premRNAs, splice-junction microarray experiments indicate that this number is at least 40% (ref. 7). Determining the diversity of mRNAs generated by alternative promoters, alternative splicing and RNA editing will substantially increase the inferred protein repertoire. Non-coding RNA genes (ncRNAs) including short interfering RNAs (siRNAs) and microRNAS (miRNAs) (reviewed in ref. 10), and longer ncRNAs such as bxd (ref. 11) and rox (ref. 12), have important roles in gene regulation, whereas others such as small nucleolar RNAs (snoRNAs)and small nuclear RNAs (snRNAs) are important components of macromolecular machines such as the ribosome and spliceosome. The transcription and processing of these ncRNAs must also be fully documented and mapped. As part of the modENCODE project to annotate the functional elements of the D. melanogaster and Caenorhabditis elegans genomes, we used RNA-Seq and tiling microarrays to sample the Drosophila transcriptome at unprecedented depth throughout development from early embryo to ageing male and female adults. We report on a high-resolution view of the discovery, structure and dynamic expression of the D. melanogaster transcriptome.« less

The complete chloroplast genome of Cinnamomum camphora and its comparison with related Lauraceae species.

PubMed

Chen, Caihui; Zheng, Yongjie; Liu, Sian; Zhong, Yongda; Wu, Yanfang; Li, Jiang; Xu, Li-An; Xu, Meng

2017-01-01

Cinnamomum camphora , a member of the Lauraceae family, is a valuable aromatic and timber tree that is indigenous to the south of China and Japan. All parts of Cinnamomum camphora have secretory cells containing different volatile chemical compounds that are utilized as herbal medicines and essential oils. Here, we reported the complete sequencing of the chloroplast genome of Cinnamomum camphora using illumina technology. The chloroplast genome of Cinnamomum camphora is 152,570 bp in length and characterized by a relatively conserved quadripartite structure containing a large single copy region of 93,705 bp, a small single copy region of 19,093 bp and two inverted repeat (IR) regions of 19,886 bp. Overall, the genome contained 123 coding regions, of which 15 were repeated in the IR regions. An analysis of chloroplast sequence divergence revealed that the small single copy region was highly variable among the different genera in the Lauraceae family. A total of 40 repeat structures and 83 simple sequence repeats were detected in both the coding and non-coding regions. A phylogenetic analysis indicated that Calycanthus is most closely related to Lauraceae , both being members of Laurales , which forms a sister group to Magnoliids . The complete sequence of the chloroplast of Cinnamomum camphora will aid in in-depth taxonomical studies of the Lauraceae family in the future. The genetic sequence information will also have valuable applications for chloroplast genetic engineering.

Capacity achieving nonbinary LDPC coded non-uniform shaping modulation for adaptive optical communications.

PubMed

Lin, Changyu; Zou, Ding; Liu, Tao; Djordjevic, Ivan B

2016-08-08

A mutual information inspired nonbinary coded modulation design with non-uniform shaping is proposed. Instead of traditional power of two signal constellation sizes, we design 5-QAM, 7-QAM and 9-QAM constellations, which can be used in adaptive optical networks. The non-uniform shaping and LDPC code rate are jointly considered in the design, which results in a better performance scheme for the same SNR values. The matched nonbinary (NB) LDPC code is used for this scheme, which further improves the coding gain and the overall performance. We analyze both coding performance and system SNR performance. We show that the proposed NB LDPC-coded 9-QAM has more than 2dB gain in symbol SNR compared to traditional LDPC-coded star-8-QAM. On the other hand, the proposed NB LDPC-coded 5-QAM and 7-QAM have even better performance than LDPC-coded QPSK.

Insertion of operation-and-indicate instructions for optimized SIMD code

DOEpatents

Eichenberger, Alexander E; Gara, Alan; Gschwind, Michael K

2013-06-04

Mechanisms are provided for inserting indicated instructions for tracking and indicating exceptions in the execution of vectorized code. A portion of first code is received for compilation. The portion of first code is analyzed to identify non-speculative instructions performing designated non-speculative operations in the first code that are candidates for replacement by replacement operation-and-indicate instructions that perform the designated non-speculative operations and further perform an indication operation for indicating any exception conditions corresponding to special exception values present in vector register inputs to the replacement operation-and-indicate instructions. The replacement is performed and second code is generated based on the replacement of the at least one non-speculative instruction. The data processing system executing the compiled code is configured to store special exception values in vector output registers, in response to a speculative instruction generating an exception condition, without initiating exception handling.

Non-binary LDPC-coded modulation for high-speed optical metro networks with backpropagation

NASA Astrophysics Data System (ADS)

Arabaci, Murat; Djordjevic, Ivan B.; Saunders, Ross; Marcoccia, Roberto M.

2010-01-01

To simultaneously mitigate the linear and nonlinear channel impairments in high-speed optical communications, we propose the use of non-binary low-density-parity-check-coded modulation in combination with a coarse backpropagation method. By employing backpropagation, we reduce the memory in the channel and in return obtain significant reductions in the complexity of the channel equalizer which is exponentially proportional to the channel memory. We then compensate for the remaining channel distortions using forward error correction based on non-binary LDPC codes. We propose non-binary-LDPC-coded modulation scheme because, compared to bit-interleaved binary-LDPC-coded modulation scheme employing turbo equalization, the proposed scheme lowers the computational complexity and latency of the overall system while providing impressively larger coding gains.

Role of RNA interference (RNAi) in the Moss Physcomitrella patens.

PubMed

Arif, Muhammad Asif; Frank, Wolfgang; Khraiwesh, Basel

2013-01-14

RNA interference (RNAi) is a mechanism that regulates genes by either transcriptional (TGS) or posttranscriptional gene silencing (PTGS), required for genome maintenance and proper development of an organism. Small non-coding RNAs are the key players in RNAi and have been intensively studied in eukaryotes. In plants, several classes of small RNAs with specific sizes and dedicated functions have evolved. The major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis. miRNAs are synthesized from a short hairpin structure while siRNAs are derived from long double-stranded RNAs (dsRNA). Both miRNA and siRNAs control the expression of cognate target RNAs by binding to reverse complementary sequences mediating cleavage or translational inhibition of the target RNA. They also act on the DNA and cause epigenetic changes such as DNA methylation and histone modifications. In the last years, the analysis of plant RNAi pathways was extended to the bryophyte Physcomitrella patens, a non-flowering, non-vascular ancient land plant that diverged from the lineage of seed plants approximately 450 million years ago. Based on a number of characteristic features and its phylogenetic key position in land plant evolution P. patens emerged as a plant model species to address basic as well as applied topics in plant biology. Here we summarize the current knowledge on the role of RNAi in P. patens that shows functional overlap with RNAi pathways from seed plants, and also unique features specific to this species.

Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression†

PubMed Central

York, Adam W.; Zhang, Yilin; Holley, Andrew C.; Guo, Yanlin; Huang, Faqing; McCormick, Charles L.

2009-01-01

Cell specific delivery of small interfering ribonucleic acid (siRNA) using well-defined multivalent folate-conjugated block copolymers is reported. Primary amine functional, biocompatible, hydrophilic-block-cationic copolymers were synthesized via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. N-(2-hydroxypropyl)methacrylamide) (HPMA), a permanently hydrophilic monomer, was copolymerized with a primary amine containing monomer, N-(3-aminopropyl)methacrylamide (APMA). Poly(HPMA) confers biocompatibility while APMA provides amine functionality allowing conjugation of folate derivatives. (HPMA-stat-APMA) was chain extended with a cationic block, poly(N-[3-(dimethylamino)propyl]methacrylamide) in order to promote electrostatic complexation between the copolymer and the negatively charged phosphate backbone of siRNA. Notably, poly(HPMA) stabilizes the neutral complexes in aqueous solution while APMA allows the conjugation of a targeting moiety, thus, dually circumventing problems associated with the delivery of genes via cationically charged complexes (universal transfection). Fluorescence microscopy and gene down-regulation studies indicate that these neutral complexes can be specifically delivered to cancer cells that over-express folate receptors. PMID:19290625

Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore

PubMed Central

Loh, Jin Phang; Gao, Qiu Han Christine; Lee, Vernon J; Tetteh, Kevin; Drakeley, Chris

2016-01-01

INTRODUCTION Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. METHODS Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. RESULTS Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. CONCLUSION The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. PMID:26805667

Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore.

PubMed

Loh, Jin Phang; Gao, Qiu Han Christine; Lee, Vernon J; Tetteh, Kevin; Drakeley, Chris

2016-12-01

Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. Copyright: © Singapore Medical Association

Preparation, purification and analyses of thirteen alkali-stable dinucleotides from ribonucleic acid

PubMed Central

Trim, A. R.; Parker, Janet E.

1970-01-01

Of the 16 alkali-stable dinucleotides known to be obtained by hydrolysis of commercial yeast RNA with alkali, 13 were prepared in quantities of the order of 10mg or more. The samples, with only one exception, contain at least 90% of dinucleotide, and spectroscopic constants and nucleotide-sequence determinations, although not conclusive, indicate a high degree of purity of these products. The small dinucleotide fraction in 150g of RNA hydrolysed with alkali (1–2% of the total nucleotides) was separated from the mononucleotides by stepwise ion-exchange chromatography on DEAE-cellulose columns and resolved into seven fractions containing from one to four different dinucleotides by electrophoresis on paper at pH3.0. These fractions were resolved into their constituent dinucleotides by chromatography in ammonium sulphate. Contamination of the products by impurities from the paper was minimized by washing it before using it for chromatography or electrophoresis and, by using a thick grade of paper (Whatman no. 17), it was possible to handle and purify relatively large quantities of nucleotides. PMID:5435489

Guardian small RNAs and sex determination.

PubMed

Katsuma, Susumu; Kawamoto, Munetaka; Kiuchi, Takashi

2014-01-01

The W chromosome of the silkworm Bombyx mori has been known to determine femaleness for more than 80 years. However, the feminizing gene has not been molecularly identified, because the B. mori W chromosome is almost fully occupied by a large number of transposable elements. The W chromosome-derived feminizing factor of B. mori was recently shown to be a female-specific PIWI-interacting RNA (piRNA). piRNAs are small RNAs that potentially repress invading "non-self" elements (e.g., transposons and virus-like elements) by associating with PIWI proteins. Our results revealed that female-specific piRNA precursors, which we named Fem, are transcribed from the sex-determining region of the W chromosome at the early embryonic stage and are processed into a single mature piRNA (Fem piRNA). Fem piRNA forms a complex with Siwi (silkworm Piwi), which cleaves a protein-coding mRNA transcribed from the Z chromosome. RNA interference of this Z-linked gene, which we named Masc, revealed that this gene encodes a protein required for masculinization and dosage compensation. Fem and Masc both participate in the ping-pong cycle of the piRNA amplification loop by associating with the 2 B. mori PIWI proteins Siwi and BmAgo3 (silkworm Ago3), respectively, indicating that the piRNA-mediated interaction between the 2 sex chromosomes is the primary signal for the B. mori sex determination cascade. Fem is a non-transposable repetitive sequence on the W chromosome, whereas Masc is a single-copy protein-coding gene. It is of great interest how the piRNA system recognizes "self "Masc mRNA as "non-self" RNA.

Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma.

PubMed

Cătană, Cristina- Sorina; Pichler, Martin; Giannelli, Gianluigi; Mader, Robert M; Berindan-Neagoe, Ioana

2017-04-25

In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination. This review details the involvement of non codingRNAs in the evolution of human colorectal carcinoma and hepatocellular carcinoma in relationship with the microenvironment. Recent research has shown that a considerable number of dysregulated non- codingRNAs could be valuable diagnostic and prognostic biomarkers in cancer. Therefore, more in-depth knowledge of the role non- codingRNAs play in stroma-tumor communication and of the complex regulatory mechanisms between ultraconserved genes and microRNAs supports the validation of future effective therapeutic targets in patients suffering from hepatocellular and colorectal carcinoma, two distinctive entities which share quite a lot common non-coding RNAs.

Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma

PubMed Central

Cătană, Cristina- Sorina; Pichler, Martin; Giannelli, Gianluigi; Mader, Robert M.; Berindan-Neagoe, Ioana

2017-01-01

In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination. This review details the involvement of non codingRNAs in the evolution of human colorectal carcinoma and hepatocellular carcinoma in relationship with the microenvironment. Recent research has shown that a considerable number of dysregulated non- codingRNAs could be valuable diagnostic and prognostic biomarkers in cancer. Therefore, more in-depth knowledge of the role non- codingRNAs play in stroma-tumor communication and of the complex regulatory mechanisms between ultraconserved genes and microRNAs supports the validation of future effective therapeutic targets in patients suffering from hepatocellular and colorectal carcinoma, two distinctive entities which share quite a lot common non-coding RNAs. PMID:28392501

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice.

PubMed

Guo, Jun; Zhou, Yuan; Cheng, Yafen; Fang, Weiwei; Hu, Gang; Wei, Jie; Lin, Yajun; Man, Yong; Guo, Lixin; Sun, Mingxiao; Cui, Qinghua; Li, Jian

2018-01-01

Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD. © 2018 The Author(s). Published by S. Karger AG, Basel.

Analysis of Antisense Expression by Whole Genome Tiling Microarrays and siRNAs Suggests Mis-Annotation of Arabidopsis Orphan Protein-Coding Genes

PubMed Central

Richardson, Casey R.; Luo, Qing-Jun; Gontcharova, Viktoria; Jiang, Ying-Wen; Samanta, Manoj; Youn, Eunseog; Rock, Christopher D.

2010-01-01

Background MicroRNAs (miRNAs) and trans-acting small-interfering RNAs (tasi-RNAs) are small (20–22 nt long) RNAs (smRNAs) generated from hairpin secondary structures or antisense transcripts, respectively, that regulate gene expression by Watson-Crick pairing to a target mRNA and altering expression by mechanisms related to RNA interference. The high sequence homology of plant miRNAs to their targets has been the mainstay of miRNA prediction algorithms, which are limited in their predictive power for other kingdoms because miRNA complementarity is less conserved yet transitive processes (production of antisense smRNAs) are active in eukaryotes. We hypothesize that antisense transcription and associated smRNAs are biomarkers which can be computationally modeled for gene discovery. Principal Findings We explored rice (Oryza sativa) sense and antisense gene expression in publicly available whole genome tiling array transcriptome data and sequenced smRNA libraries (as well as C. elegans) and found evidence of transitivity of MIRNA genes similar to that found in Arabidopsis. Statistical analysis of antisense transcript abundances, presence of antisense ESTs, and association with smRNAs suggests several hundred Arabidopsis ‘orphan’ hypothetical genes are non-coding RNAs. Consistent with this hypothesis, we found novel Arabidopsis homologues of some MIRNA genes on the antisense strand of previously annotated protein-coding genes. A Support Vector Machine (SVM) was applied using thermodynamic energy of binding plus novel expression features of sense/antisense transcription topology and siRNA abundances to build a prediction model of miRNA targets. The SVM when trained on targets could predict the “ancient” (deeply conserved) class of validated Arabidopsis MIRNA genes with an accuracy of 84%, and 76% for “new” rapidly-evolving MIRNA genes. Conclusions Antisense and smRNA expression features and computational methods may identify novel MIRNA genes and other non-coding RNAs in plants and potentially other kingdoms, which can provide insight into antisense transcription, miRNA evolution, and post-transcriptional gene regulation. PMID:20520764

High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells

PubMed Central

Gonçalves da Silva, Patrícia Benites; Teixeira dos Santos, Márcia Cristina; Rodini, Carolina Oliveira; Kaid, Carolini; Leite Pereira, Márcia Cristina; Furukawa, Gabriela; Gimenes da Cruz, Daniel Sanzio; Goldfeder, Mauricio Barbugiani; Reily Rocha, Clarissa Ribeiro; Rosenberg, Carla; Okamoto, Oswaldo Keith

2017-01-01

Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates. Pro-oncogenic OCT4A effects were expression-level dependent and accompanied by distinct chromosomal aberrations. OCT4A overexpression in medulloblastoma cells also induced a marked differential expression of non-coding RNAs, including poorly characterized long non-coding RNAs and small nucleolar RNAs. Altogether, our findings support the relevance of pluripotency-related factors in the aggravation of medulloblastoma traits classically associated with poor clinical outcome, and underscore the prognostic and therapeutic value of OCT4A in this challenging type of pediatric brain cancer. PMID:28186969

High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells.

PubMed

da Silva, Patrícia Benites Gonçalves; Teixeira Dos Santos, Márcia Cristina; Rodini, Carolina Oliveira; Kaid, Carolini; Pereira, Márcia Cristina Leite; Furukawa, Gabriela; da Cruz, Daniel Sanzio Gimenes; Goldfeder, Mauricio Barbugiani; Rocha, Clarissa Ribeiro Reily; Rosenberg, Carla; Okamoto, Oswaldo Keith

2017-03-21

Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates. Pro-oncogenic OCT4A effects were expression-level dependent and accompanied by distinct chromosomal aberrations. OCT4A overexpression in medulloblastoma cells also induced a marked differential expression of non-coding RNAs, including poorly characterized long non-coding RNAs and small nucleolar RNAs. Altogether, our findings support the relevance of pluripotency-related factors in the aggravation of medulloblastoma traits classically associated with poor clinical outcome, and underscore the prognostic and therapeutic value of OCT4A in this challenging type of pediatric brain cancer.

The presence of Epstein-Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on 'EBV-positive DLBCL of the elderly'.

PubMed

Uner, Aysegul; Akyurek, Nalan; Saglam, Arzu; Abdullazade, Samir; Uzum, Nuket; Onder, Sevgen; Barista, Ibrahim; Benekli, Mustafa

2011-04-01

Accumulated evidence has shown the importance of Epstein-Barr virus in the pathogenesis of various lymphomas. This study aimed to determine the prevalence of Epstein-Barr virus expression and its effect on survival amongst diffuse large B-cell lymphoma (DLBCL) cases from two large tertiary care centres in Turkey with a particular interest in identifying cases of 'Epstein-Barr virus-positive DLBCL of the elderly'. Diffuse large B-cell lymphoma cases diagnosed between 1999 and 2009 were retrieved and 340 cases were used to construct tissue microarrays. The presence of Epstein-Barr virus small ribonucleic acids was examined by in situ hybridization using Epstein-Barr virus (EBV)-encoded small RNA (EBER) oligonucleotides. A total of 18 cases (5.3%) showed Epstein-Barr virus expression. Twelve cases were classified as Epstein-Barr virus-positive DLBCL of the elderly. Epstein-Barr virus-positive DLBCL cases showed a significantly inferior overall survival as compared with Epstein-Barr virus-negative cases (p < 0.001). In our study group Epstein-Barr virus expression is not prevalent in DLBCLs. Epstein-Barr virus-positive DLBCL of the elderly is also rare in the Turkish population. The presence of Epstein-Barr virus, however, is associated with poor prognosis. © 2011 The Authors. APMIS © 2011 APMIS.

Draft genome sequence of carbapenem-resistant Shewanella algae strain AC isolated from small abalone (Haliotis diversicolor).

PubMed

Huang, Yao-Ting; Cheng, Jan-Fang; Chen, Shi-Yu; Hong, Yu-Kai; Wu, Zong-Yen; Liu, Po-Yu

2018-06-19

Shewanella algae is an environmental marine bacteria and an emerging opportunistic human pathogen. Moreover, there are increasing reports of strains showing multi-drug resistance, particularly carbapenem-resistant isolates. Although S. algae have been found in bivalve shellfish aquaculture, there is very little genome-wide data on resistant determinants in S. algae from shellfish. In the study, we aimed to determine the whole genome sequence of carbapenem-resistant S. algae strain AC isolated from small abalone in Taiwan. Genome DNA was sequenced using an Illumina MiSeq platform using 250bp paired-end reads. De novo genome assembly was performed using Velvet v1.2.07. The whole genome was annotated and several candidate genes for antimicrobial resistance were identified. The genome size was calculated at 4,751,156bp, with a mean G＋C content of 53.09%. A total of 4,164 protein-coding sequences, 7 rRNAs, 85 tRNAs, and 5 non-coding RNAs were identified. The genome contains genes associated with resistance to β-lactams, trimethoprim, tetracycline, colistin, and quinolone resistance. Multiple efflux pump genes were also detected. Small abalone is a potential source of foodborne drug resistant S. algae. The genome sequence of a carbapenem-resistant S. algae strain AC isolated from small abalone will provide valuable information for further study of the dissemination of resistance genes at the human-animal interface. Copyright © 2018. Published by Elsevier Ltd.

The effects of potato virus Y-derived virus small interfering RNAs of three biologically distinct strains on potato (Solanum tuberosum) transcriptome.

PubMed

Moyo, Lindani; Ramesh, Shunmugiah V; Kappagantu, Madhu; Mitter, Neena; Sathuvalli, Vidyasagar; Pappu, Hanu R

2017-07-17

Potato virus Y (PVY) is one of the most economically important pathogen of potato that is present as biologically distinct strains. The virus-derived small interfering RNAs (vsiRNAs) from potato cv. Russet Burbank individually infected with PVY-N, PVY-NTN and PVY-O strains were recently characterized. Plant defense RNA-silencing mechanisms deployed against viruses produce vsiRNAs to degrade homologous viral transcripts. Based on sequence complementarity, the vsiRNAs can potentially degrade host RNA transcripts raising the prospect of vsiRNAs as pathogenicity determinants in virus-host interactions. This study investigated the global effects of PVY vsiRNAs on the host potato transcriptome. The strain-specific vsiRNAs of PVY, expressed in high copy number, were analyzed in silico for their proclivity to target potato coding and non-coding RNAs using psRobot and psRNATarget algorithms. Functional annotation of target coding transcripts was carried out to predict physiological effects of the vsiRNAs on the potato cv. Russet Burbank. The downregulation of selected target coding transcripts was further validated using qRT-PCR. The vsiRNAs derived from biologically distinct strains of PVY displayed diversity in terms of absolute number, copy number and hotspots for siRNAs on their respective genomes. The vsiRNAs populations were derived with a high frequency from 6 K1, P1 and Hc-Pro for PVY-N, P1, Hc-Pro and P3 for PVY-NTN, and P1, 3' UTR and NIa for PVY-O genomic regions. The number of vsiRNAs that displayed interaction with potato coding transcripts and number of putative coding target transcripts were comparable between PVY-N and PVY-O, and were relatively higher for PVY-NTN. The most abundant target non-coding RNA transcripts for the strain specific PVY-derived vsiRNAs were found to be MIR821, 28S rRNA,18S rRNA, snoR71, tRNA-Met and U5. Functional annotation and qRT-PCR validation suggested that the vsiRNAs target genes involved in plant hormone signaling, genetic information processing, plant-pathogen interactions, plant defense and stress response processes in potato. The findings suggested that the PVY-derived vsiRNAs could act as a pathogenicity determinant and as a counter-defense strategy to host RNA silencing in PVY-potato interactions. The broad range of host genes targeted by PVY vsiRNAs in infected potato suggests a diverse role for vsiRNAs that includes suppression of host stress responses and developmental processes. The interactome scenario is the first report on the interaction between one of the most important Potyvirus genome-derived siRNAs and the potato transcripts.

Modeling coherent errors in quantum error correction

NASA Astrophysics Data System (ADS)

Greenbaum, Daniel; Dutton, Zachary

2018-01-01

Analysis of quantum error correcting codes is typically done using a stochastic, Pauli channel error model for describing the noise on physical qubits. However, it was recently found that coherent errors (systematic rotations) on physical data qubits result in both physical and logical error rates that differ significantly from those predicted by a Pauli model. Here we examine the accuracy of the Pauli approximation for noise containing coherent errors (characterized by a rotation angle ɛ) under the repetition code. We derive an analytic expression for the logical error channel as a function of arbitrary code distance d and concatenation level n, in the small error limit. We find that coherent physical errors result in logical errors that are partially coherent and therefore non-Pauli. However, the coherent part of the logical error is negligible at fewer than {ε }-({dn-1)} error correction cycles when the decoder is optimized for independent Pauli errors, thus providing a regime of validity for the Pauli approximation. Above this number of correction cycles, the persistent coherent logical error will cause logical failure more quickly than the Pauli model would predict, and this may need to be combated with coherent suppression methods at the physical level or larger codes.

Upregulation of the long non-coding RNA SNHG1 predicts poor prognosis, promotes cell proliferation and invasion, and reduces apoptosis in glioma.

PubMed

Wang, Qiang; Li, Qing; Zhou, Peng; Deng, Danni; Xue, Lian; Shao, Naiyuan; Peng, Ya; Zhi, Feng

2017-07-01

Long non-coding RNAs (lncRNAs), which are non-coding RNAs with a length above 200 nucleotides, have emerged as novel and important gene expression modulators in carcinogenesis. Recent evidence indicates that the lncRNA small nucleolar RNA host gene 1 (SNHG1) functions as an oncogene in several types of human cancers. However, its function in the development of glioma remains unknown. The aim of this research was to investigate the clinical aspects and biological mechanisms of SNHG1 in glioma. SNHG1 expression was measured in glioma tissues and cell lines by quantitative real-time PCR (qRT-PCR). The association between SNHG1 expression in tissues and clinicopathological characteristics and prognosis in glioma patients was also explored. Gain-of-function and loss-of-function studies using SNHG1 cDNA and siRNA, respectively, were used to investigate the role of SNHG1 in cell proliferation, invasion and apoptosis in glioma. SNHG1 was highly expressed in glioma tissues, and its upregulation was closely related to old age. Kaplan-Meier analysis showed that high expression of SNHG1 was significantly associated with poor overall survival (OS). Functionally, ectopic expression of SNHG1 enhanced cell proliferation and cell invasion and reduced cell apoptosis in vitro, while SNHG1 knockdown reversed these effects. Taken together, our findings indicate that SNHG1 functions as an oncogene in glioma and may serve as a novel therapeutic target in future treatments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Optimal periodic binary codes of lengths 28 to 64

NASA Technical Reports Server (NTRS)

Tyler, S.; Keston, R.

1980-01-01

Results from computer searches performed to find repeated binary phase coded waveforms with optimal periodic autocorrelation functions are discussed. The best results for lengths 28 to 64 are given. The code features of major concern are where (1) the peak sidelobe in the autocorrelation function is small and (2) the sum of the squares of the sidelobes in the autocorrelation function is small.

SYMTRAN - A Time-dependent Symmetric Tandem Mirror Transport Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, D; Fowler, T

2004-06-15

A time-dependent version of the steady-state radial transport model in symmetric tandem mirrors in Ref. [1] has been coded up and first tests performed. Our code, named SYMTRAN, is an adaptation of the earlier SPHERE code for spheromaks, now modified for tandem mirror physics. Motivated by Post's new concept of kinetic stabilization of symmetric mirrors, it is an extension of the earlier TAMRAC rate-equation code omitting radial transport [2], which successfully accounted for experimental results in TMX. The SYMTRAN code differs from the earlier tandem mirror radial transport code TMT in that our code is focused on axisymmetric tandem mirrorsmore » and classical diffusion, whereas TMT emphasized non-ambipolar transport in TMX and MFTF-B due to yin-yang plugs and non-symmetric transitions between the plugs and axisymmetric center cell. Both codes exhibit interesting but different non-linear behavior.« less

Novel insights into the response of Atlantic salmon (Salmo salar) to Piscirickettsia salmonis: Interplay of coding genes and lncRNAs during bacterial infection.

PubMed

Valenzuela-Miranda, Diego; Gallardo-Escárate, Cristian

2016-12-01

Despite the high prevalence and impact to Chilean salmon aquaculture of the intracellular bacterium Piscirickettsia salmonis, the molecular underpinnings of host-pathogen interactions remain unclear. Herein, the interplay of coding and non-coding transcripts has been proposed as a key mechanism involved in immune response. Therefore, the aim of this study was to evidence how coding and non-coding transcripts are modulated during the infection process of Atlantic salmon with P. salmonis. For this, RNA-seq was conducted in brain, spleen, and head kidney samples, revealing different transcriptional profiles according to bacterial load. Additionally, while most of the regulated genes annotated for diverse biological processes during infection, a common response associated with clathrin-mediated endocytosis and iron homeostasis was present in all tissues. Interestingly, while endocytosis-promoting factors and clathrin inductions were upregulated, endocytic receptors were mainly downregulated. Furthermore, the regulation of genes related to iron homeostasis suggested an intracellular accumulation of iron, a process in which heme biosynthesis/degradation pathways might play an important role. Regarding the non-coding response, 918 putative long non-coding RNAs were identified, where 425 were newly characterized for S. salar. Finally, co-localization and co-expression analyses revealed a strong correlation between the modulations of long non-coding RNAs and genes associated with endocytosis and iron homeostasis. These results represent the first comprehensive study of putative interplaying mechanisms of coding and non-coding RNAs during bacterial infection in salmonids. Copyright © 2016 Elsevier Ltd. All rights reserved.

sRNAdb: A small non-coding RNA database for gram-positive bacteria

PubMed Central

2012-01-01

Background The class of small non-coding RNA molecules (sRNA) regulates gene expression by different mechanisms and enables bacteria to mount a physiological response due to adaptation to the environment or infection. Over the last decades the number of sRNAs has been increasing rapidly. Several databases like Rfam or fRNAdb were extended to include sRNAs as a class of its own. Furthermore new specialized databases like sRNAMap (gram-negative bacteria only) and sRNATarBase (target prediction) were established. To the best of the authors’ knowledge no database focusing on sRNAs from gram-positive bacteria is publicly available so far. Description In order to understand sRNA’s functional and phylogenetic relationships we have developed sRNAdb and provide tools for data analysis and visualization. The data compiled in our database is assembled from experiments as well as from bioinformatics analyses. The software enables comparison and visualization of gene loci surrounding the sRNAs of interest. To accomplish this, we use a client–server based approach. Offline versions of the database including analyses and visualization tools can easily be installed locally on the user’s computer. This feature facilitates customized local addition of unpublished sRNA candidates and related information such as promoters or terminators using tab-delimited files. Conclusion sRNAdb allows a user-friendly and comprehensive comparative analysis of sRNAs from available sequenced gram-positive prokaryotic replicons. Offline versions including analysis and visualization tools facilitate complex user specific bioinformatics analyses. PMID:22883983

Association of Genetic Variants of Small Non-Coding RNAs with Survival in Colorectal Cancer

PubMed Central

Pao, Jiunn-Bey; Lu, Te-Ling; Ting, Wen-Chien; Chen, Lu-Min; Bao, Bo-Ying

2018-01-01

Background: Single nucleotide polymorphisms (SNPs) of small non-coding RNAs (sncRNAs) can influence sncRNA function and target gene expression to mediate the risk of certain diseases. The aim of the present study was to evaluate the prognostic relevance of sncRNA SNPs for colorectal cancer, which has not been well characterized to date. Methods: We comprehensively examined 31 common SNPs of sncRNAs, and assessed the impact of these variants on survival in a cohort of 188 patients with colorectal cancer. Results: Three SNPs were significantly associated with survival of patients with colorectal cancer after correction for multiple testing, and two of the SNPs (hsa-mir-196a-2 rs11614913 and U85 rs714775) remained significant in multivariate analyses. Additional in silico analysis provided further evidence of this association, since the expression levels of the target genes of the hsa-miR-196a (HOXA7, HOXB8, and AKT1) were significantly correlated with colorectal cancer progression. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that hsa-miR-196a is associated with well-known oncogenic pathways, including cellular protein modification process, mitotic cell cycle, adherens junction, and extracellular matrix receptor interaction pathways. Conclusion: Our results suggest that SNPs of sncRNAs could play a critical role in cancer progression, and that hsa-miR-196a might be a valuable biomarker or therapeutic target for colorectal cancer patients. PMID:29483812

RNA isolation from mammalian cells using porous polymer monoliths: an approach for high-throughput automation.

PubMed

Chatterjee, Anirban; Mirer, Paul L; Zaldivar Santamaria, Elvira; Klapperich, Catherine; Sharon, Andre; Sauer-Budge, Alexis F

2010-06-01

The life science and healthcare communities have been redefining the importance of ribonucleic acid (RNA) through the study of small molecule RNA (in RNAi/siRNA technologies), micro RNA (in cancer research and stem cell research), and mRNA (gene expression analysis for biologic drug targets). Research in this field increasingly requires efficient and high-throughput isolation techniques for RNA. Currently, several commercial kits are available for isolating RNA from cells. Although the quality and quantity of RNA yielded from these kits is sufficiently good for many purposes, limitations exist in terms of extraction efficiency from small cell populations and the ability to automate the extraction process. Traditionally, automating a process decreases the cost and personnel time while simultaneously increasing the throughput and reproducibility. As the RNA field matures, new methods for automating its extraction, especially from low cell numbers and in high throughput, are needed to achieve these improvements. The technology presented in this article is a step toward this goal. The method is based on a solid-phase extraction technology using a porous polymer monolith (PPM). A novel cell lysis approach and a larger binding surface throughout the PPM extraction column ensure a high yield from small starting samples, increasing sensitivity and reducing indirect costs in cell culture and sample storage. The method ensures a fast and simple procedure for RNA isolation from eukaryotic cells, with a high yield both in terms of quality and quantity. The technique is amenable to automation and streamlined workflow integration, with possible miniaturization of the sample handling process making it suitable for high-throughput applications.

Far-red fluorescent probes for canonical and non-canonical nucleic acid structures: current progress and future implications.

PubMed

Suseela, Y V; Narayanaswamy, Nagarjun; Pratihar, Sumon; Govindaraju, Thimmaiah

2018-02-05

The structural diversity and functional relevance of nucleic acids (NAs), mainly deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are indispensable for almost all living organisms, with minute aberrations in their structure and function becoming causative factors in numerous human diseases. The standard structures of NAs, termed canonical structures, are supported by Watson-Crick hydrogen bonding. Under special physiological conditions, NAs adopt distinct spatial organisations, giving rise to non-canonical conformations supported by hydrogen bonding other than the Watson-Crick type; such non-canonical structures have a definite function in controlling gene expression and are considered as novel diagnostic and therapeutic targets. Development of molecular probes for these canonical and non-canonical DNA/RNA structures has been an active field of research. Among the numerous probes studied, probes with turn-on fluorescence in the far-red (600-750 nm) region are highly sought-after due to minimal autofluorescence and cellular damage. Far-red fluorescent probes are vital for real-time imaging of NAs in live cells as they provide good resolution and minimal perturbation of the cell under investigation. In this review, we present recent advances in the area of far-red fluorescent probes of DNA/RNA and non-canonical G-quadruplex structures. For the sake of continuity and completeness, we provide a brief overview of visible fluorescent probes. Utmost importance is given to design criteria, characteristic properties and biological applications, including in cellulo imaging, apart from critical discussion on limitations of the far-red fluorescent probes. Finally, we offer current and future prospects in targeting canonical and non-canonical NAs specific to cellular organelles, through sequence- and conformation-specific far-red fluorescent probes. We also cover their implications in chemical and molecular biology, with particular focus on decoding various disease mechanisms involving NAs.

48 CFR 52.212-1 - Instructions to Offerors-Commercial Items.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Classification System (NAICS) code and small business size standard. The NAICS code and small business size... Government infrastructure not later than 5:00 p.m. one working day prior to the date specified for receipt of...

Annual Research Report 1 October 1978-30 September 1979.

DTIC Science & Technology

1979-01-01

Roeder, R. G. and Rutter, W. J. Multiple acid polymerases in ribonucleic acid synthesis during sea urchin development. Biochemistry 9: 2543-2554...with ultrastructural transmission electron microscopy (TEM) studies and scanning electron microscopy ( SEM ) stud- ies of lateral ventricular lining and...1I alterations in animals about 100 days after Silastic implantation. SEM studies show flattening and stretching of ependymal cells in the dorsomedial

Optimisation of high-quality total ribonucleic acid isolation from cartilaginous tissues for real-time polymerase chain reaction analysis.

PubMed

Peeters, M; Huang, C L; Vonk, L A; Lu, Z F; Bank, R A; Helder, M N; Doulabi, B Zandieh

2016-11-01

Studies which consider the molecular mechanisms of degeneration and regeneration of cartilaginous tissues are seriously hampered by problematic ribonucleic acid (RNA) isolations due to low cell density and the dense, proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co-purify with RNA, they can absorb the full spectrum of UV light and they are potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of the present study is to compare and optimise different homogenisation methods and RNA isolation kits for an array of cartilaginous tissues. Tissue samples such as the nucleus pulposus (NP), annulus fibrosus (AF), articular cartilage (AC) and meniscus, were collected from goats and homogenised by either the MagNA Lyser or Freezer Mill. RNA of duplicate samples was subsequently isolated by either TRIzol (benchmark), or the RNeasy Lipid Tissue, RNeasy Fibrous Tissue, or Aurum Total RNA Fatty and Fibrous Tissue kits. RNA yield, purity, and integrity were determined and gene expression levels of type II collagen and aggrecan were measured by real-time PCR. No differences between the two homogenisation methods were found. RNA isolation using the RNeasy Fibrous and Lipid kits resulted in the purest RNA (A260/A280 ratio), whereas TRIzol isolations resulted in RNA that is not as pure, and show a larger difference in gene expression of duplicate samples compared with both RNeasy kits. The Aurum kit showed low reproducibility. For the extraction of high-quality RNA from cartilaginous structures, we suggest homogenisation of the samples by the MagNA Lyser. For AC, NP and AF we recommend the RNeasy Fibrous kit, whereas for the meniscus the RNeasy Lipid kit is advised.Cite this article: M. Peeters, C. L. Huang, L. A. Vonk, Z. F. Lu, R. A. Bank, M. N. Helder, B. Zandieh Doulabi. Optimisation of high-quality total ribonucleic acid isolation from cartilaginous tissues for real-time polymerase chain reaction analysis. Bone Joint Res 2016;5:560-568. DOI: 10.1302/2046-3758.511.BJR-2016-0033.R3. © 2016 Peeters et al.

Optimisation of high-quality total ribonucleic acid isolation from cartilaginous tissues for real-time polymerase chain reaction analysis

PubMed Central

Peeters, M.; Huang, C. L.; Vonk, L. A.; Lu, Z. F.; Bank, R. A.; Doulabi, B. Zandieh

2016-01-01

Objectives Studies which consider the molecular mechanisms of degeneration and regeneration of cartilaginous tissues are seriously hampered by problematic ribonucleic acid (RNA) isolations due to low cell density and the dense, proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co-purify with RNA, they can absorb the full spectrum of UV light and they are potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of the present study is to compare and optimise different homogenisation methods and RNA isolation kits for an array of cartilaginous tissues. Materials and Methods Tissue samples such as the nucleus pulposus (NP), annulus fibrosus (AF), articular cartilage (AC) and meniscus, were collected from goats and homogenised by either the MagNA Lyser or Freezer Mill. RNA of duplicate samples was subsequently isolated by either TRIzol (benchmark), or the RNeasy Lipid Tissue, RNeasy Fibrous Tissue, or Aurum Total RNA Fatty and Fibrous Tissue kits. RNA yield, purity, and integrity were determined and gene expression levels of type II collagen and aggrecan were measured by real-time PCR. Results No differences between the two homogenisation methods were found. RNA isolation using the RNeasy Fibrous and Lipid kits resulted in the purest RNA (A260/A280 ratio), whereas TRIzol isolations resulted in RNA that is not as pure, and show a larger difference in gene expression of duplicate samples compared with both RNeasy kits. The Aurum kit showed low reproducibility. Conclusion For the extraction of high-quality RNA from cartilaginous structures, we suggest homogenisation of the samples by the MagNA Lyser. For AC, NP and AF we recommend the RNeasy Fibrous kit, whereas for the meniscus the RNeasy Lipid kit is advised. Cite this article: M. Peeters, C. L. Huang, L. A. Vonk, Z. F. Lu, R. A. Bank, M. N. Helder, B. Zandieh Doulabi. Optimisation of high-quality total ribonucleic acid isolation from cartilaginous tissues for real-time polymerase chain reaction analysis. Bone Joint Res 2016;5:560–568. DOI: 10.1302/2046-3758.511.BJR-2016-0033.R3. PMID:27881439

Down-regulation of long non-coding RNA MEG3 indicates an unfavorable prognosis in non-small cell lung cancer: Evidence from the GEO database.

PubMed

Zhang, Zichao; Liu, Tiantian; Wang, Kai; Qu, Xiao; Pang, Zhaofei; Liu, Shaorui; Liu, Qi; Du, Jiajun

2017-09-30

Long non-coding RNA (lncRNA) MEG3 (maternally expressed gene 3) is an imprinted gene that suppresses cells growth in various tumors. However, the association between MEG3 expression and prognosis in non-small cell lung cancer (NSCLC) has not been fully investigated. Seven datasets with 1144 patients were obtained from Gene Expression Omnibus (GEO) database (Affymetrix U133 Plus 2.0 platform). Association between MEG3 and other variables was tested using the chi-squared test. Kaplan-Meier survival analysis was carried out to explore the association between MEG3 expression and overall survival (OS)/progression free survival (PFS). Results of univariate and multivariate Cox regression analysis were represented in HR and 95%CI form. Summarized results and publication bias were showed by forest plots and funnel plots respectively. Differential expression of MEG3 was related to stage (GSE31210OS and GSE31210PFS), histology (GSE29013OS and GSE29013PFS) and gender (GSE29013PFS). In summary, low MEG3 expression was associated with shorter long-term survival time in several datasets (GSE3141 (p=0.039), GSE30219 (p=0.008) for OS and GSE30219 (p=0.048) for PFS). We found that MEG3 was an independent prognostic factor in GSE30219 for PFS (HR 0.666, 95%CI 0.458-0.969, p=0.033). The summarized results suggested that low MEG3 expression was a poor prognostic factor in NSCLC (HR=0.77, 95%CI 0.63-0.95). Specifically, the association between low MEG3 expression and poor prognosis was markedly significant in younger patients (≤60years old) (HR0.602, 95%CI 0.417-0.867, p=0.007). These findings indicate that MEG3 could be a novel prognostic factor for NSCLC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

u-Constacyclic codes over F_p+u{F}_p and their applications of constructing new non-binary quantum codes

NASA Astrophysics Data System (ADS)

Gao, Jian; Wang, Yongkang

2018-01-01

Structural properties of u-constacyclic codes over the ring F_p+u{F}_p are given, where p is an odd prime and u^2=1. Under a special Gray map from F_p+u{F}_p to F_p^2, some new non-binary quantum codes are obtained by this class of constacyclic codes.

Genome wide discovery of long intergenic non-coding RNAs in Diamondback moth (Plutella xylostella) and their expression in insecticide resistant strains

PubMed Central

Etebari, Kayvan; Furlong, Michael J.; Asgari, Sassan

2015-01-01

Long non-coding RNAs (lncRNAs) play important roles in genomic imprinting, cancer, differentiation and regulation of gene expression. Here, we identified 3844 long intergenic ncRNAs (lincRNA) in Plutella xylostella, which is a notorious pest of cruciferous plants that has developed field resistance to all classes of insecticides, including Bacillus thuringiensis (Bt) endotoxins. Further, we found that some of those lincRNAs may potentially serve as precursors for the production of small ncRNAs. We found 280 and 350 lincRNAs that are differentially expressed in Chlorpyrifos and Fipronil resistant larvae. A survey on P. xylostella midgut transcriptome data from Bt-resistant populations revealed 59 altered lincRNA in two resistant strains compared with the susceptible population. We validated the transcript levels of a number of putative lincRNAs in deltamethrin-resistant larvae that were exposed to deltamethrin, which indicated that this group of lincRNAs might be involved in the response to xenobiotics in this insect. To functionally characterize DBM lincRNAs, gene ontology (GO) enrichment of their associated protein-coding genes was extracted and showed over representation of protein, DNA and RNA binding GO terms. The data presented here will facilitate future studies to unravel the function of lincRNAs in insecticide resistance or the response to xenobiotics of eukaryotic cells. PMID:26411386

The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy.

PubMed

Kwon, Yong Tae; Ciechanover, Aaron

2017-11-01

The conjugation of the 76 amino acid protein ubiquitin to other proteins can alter the metabolic stability or non-proteolytic functions of the substrate. Once attached to a substrate (monoubiquitination), ubiquitin can itself be ubiquitinated on any of its seven lysine (Lys) residues or its N-terminal methionine (Met1). A single ubiquitin polymer may contain mixed linkages and/or two or more branches. In addition, ubiquitin can be conjugated with ubiquitin-like modifiers such as SUMO or small molecules such as phosphate. The diverse ways to assemble ubiquitin chains provide countless means to modulate biological processes. We overview here the complexity of the ubiquitin code, with an emphasis on the emerging role of linkage-specific degradation signals (degrons) in the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system (hereafter autophagy). Copyright © 2017 Elsevier Ltd. All rights reserved.

Small and Smaller—sRNAs and MicroRNAs in the Regulation of Toxin Gene Expression in Prokaryotic Cells: A Mini-Review

PubMed Central

Bloch, Sylwia; Węgrzyn, Alicja; Węgrzyn, Grzegorz; Nejman-Faleńczyk, Bożena

2017-01-01

Non-coding small RNAs (sRNAs) have been identified in the wide range of bacteria (also pathogenic species) and found to play an important role in the regulation of many processes, including toxin gene expression. The best characterized prokaryotic sRNAs regulate gene expression by base pairing with mRNA targets and fall into two broad classes: cis-encoded sRNAs (also called antisense RNA) and trans-acting sRNAs. Molecules from the second class are frequently considered as the most related to eukaryotic microRNAs. Interestingly, typical microRNA-size RNA molecules have also been reported in prokaryotic cells, although they have received little attention up to now. In this work we have collected information about all three types of small prokaryotic RNAs in the context of the regulation of toxin gene expression. PMID:28556797

Small and Smaller-sRNAs and MicroRNAs in the Regulation of Toxin Gene Expression in Prokaryotic Cells: A Mini-Review.

PubMed

Bloch, Sylwia; Węgrzyn, Alicja; Węgrzyn, Grzegorz; Nejman-Faleńczyk, Bożena

2017-05-30

Non-coding small RNAs (sRNAs) have been identified in the wide range of bacteria (also pathogenic species) and found to play an important role in the regulation of many processes, including toxin gene expression. The best characterized prokaryotic sRNAs regulate gene expression by base pairing with mRNA targets and fall into two broad classes: cis -encoded sRNAs (also called antisense RNA) and trans -acting sRNAs. Molecules from the second class are frequently considered as the most related to eukaryotic microRNAs. Interestingly, typical microRNA-size RNA molecules have also been reported in prokaryotic cells, although they have received little attention up to now. In this work we have collected information about all three types of small prokaryotic RNAs in the context of the regulation of toxin gene expression.

Constacyclic codes over the ring F_q+v{F}_q+v2F_q and their applications of constructing new non-binary quantum codes

NASA Astrophysics Data System (ADS)

Ma, Fanghui; Gao, Jian; Fu, Fang-Wei

2018-06-01

Let R={F}_q+v{F}_q+v2{F}_q be a finite non-chain ring, where q is an odd prime power and v^3=v. In this paper, we propose two methods of constructing quantum codes from (α +β v+γ v2)-constacyclic codes over R. The first one is obtained via the Gray map and the Calderbank-Shor-Steane construction from Euclidean dual-containing (α +β v+γ v2)-constacyclic codes over R. The second one is obtained via the Gray map and the Hermitian construction from Hermitian dual-containing (α +β v+γ v2)-constacyclic codes over R. As an application, some new non-binary quantum codes are obtained.

Identification of Novel Long Non-coding and Circular RNAs in Human Papillomavirus-Mediated Cervical Cancer

PubMed Central

Wang, Hongbo; Zhao, Yingchao; Chen, Mingyue; Cui, Jie

2017-01-01

Cervical cancer is the third most common cancer worldwide and the fourth leading cause of cancer-associated mortality in women. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) may play key roles in the carcinogenesis of different cancers; however, little is known about the mechanisms of lncRNAs and circRNAs in the progression and metastasis of cervical cancer. In this study, we explored the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in HPV16 (human papillomavirus genotype 16) mediated cervical squamous cell carcinoma and matched adjacent non-tumor (ATN) tissues from three patients with high-throughput RNA sequencing (RNA-seq). In total, we identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were commonly differentially expressed (DE) in different patients. Among the non-coding RNAs, 3 lncRNAs and 44 circRNAs are novel to our knowledge. Functional enrichment analysis showed that DE lncRNAs, miRNAs, and mRNAs were enriched in pathways crucial to cancer as well as other gene ontology (GO) terms. Furthermore, the co-expression network and function prediction suggested that all 19 DE lncRNAs could play different roles in the carcinogenesis and development of cervical cancer. The competing endogenous RNA (ceRNA) network based on DE coding and non-coding RNAs showed that each miRNA targeted a number of lncRNAs and circRNAs. The link between part of the miRNAs in the network and cervical cancer has been validated in previous studies, and these miRNAs targeted the majority of the novel non-coding RNAs, thus suggesting that these novel non-coding RNAs may be involved in cervical cancer. Taken together, our study shows that DE non-coding RNAs could be further developed as diagnostic and therapeutic biomarkers of cervical cancer. The complex ceRNA network also lays the foundation for future research of the roles of coding and non-coding RNAs in cervical cancer. PMID:28970820

The Mystery Behind the Code: Differentiated Instruction with Quick Response Codes in Secondary Physical Education

ERIC Educational Resources Information Center

Adkins, Megan; Wajciechowski, Misti R.; Scantling, Ed

2013-01-01

Quick response codes, better known as QR codes, are small barcodes scanned to receive information about a specific topic. This article explains QR code technology and the utility of QR codes in the delivery of physical education instruction. Consideration is given to how QR codes can be used to accommodate learners of varying ability levels as…

Incremental Parallelization of Non-Data-Parallel Programs Using the Charon Message-Passing Library

NASA Technical Reports Server (NTRS)

VanderWijngaart, Rob F.

2000-01-01

Message passing is among the most popular techniques for parallelizing scientific programs on distributed-memory architectures. The reasons for its success are wide availability (MPI), efficiency, and full tuning control provided to the programmer. A major drawback, however, is that incremental parallelization, as offered by compiler directives, is not generally possible, because all data structures have to be changed throughout the program simultaneously. Charon remedies this situation through mappings between distributed and non-distributed data. It allows breaking up the parallelization into small steps, guaranteeing correctness at every stage. Several tools are available to help convert legacy codes into high-performance message-passing programs. They usually target data-parallel applications, whose loops carrying most of the work can be distributed among all processors without much dependency analysis. Others do a full dependency analysis and then convert the code virtually automatically. Even more toolkits are available that aid construction from scratch of message passing programs. None, however, allows piecemeal translation of codes with complex data dependencies (i.e. non-data-parallel programs) into message passing codes. The Charon library (available in both C and Fortran) provides incremental parallelization capabilities by linking legacy code arrays with distributed arrays. During the conversion process, non-distributed and distributed arrays exist side by side, and simple mapping functions allow the programmer to switch between the two in any location in the program. Charon also provides wrapper functions that leave the structure of the legacy code intact, but that allow execution on truly distributed data. Finally, the library provides a rich set of communication functions that support virtually all patterns of remote data demands in realistic structured grid scientific programs, including transposition, nearest-neighbor communication, pipelining, gather/scatter, and redistribution. At the end of the conversion process most intermediate Charon function calls will have been removed, the non-distributed arrays will have been deleted, and virtually the only remaining Charon functions calls are the high-level, highly optimized communications. Distribution of the data is under complete control of the programmer, although a wide range of useful distributions is easily available through predefined functions. A crucial aspect of the library is that it does not allocate space for distributed arrays, but accepts programmer-specified memory. This has two major consequences. First, codes parallelized using Charon do not suffer from encapsulation; user data is always directly accessible. This provides high efficiency, and also retains the possibility of using message passing directly for highly irregular communications. Second, non-distributed arrays can be interpreted as (trivial) distributions in the Charon sense, which allows them to be mapped to truly distributed arrays, and vice versa. This is the mechanism that enables incremental parallelization. In this paper we provide a brief introduction of the library and then focus on the actual steps in the parallelization process, using some representative examples from, among others, the NAS Parallel Benchmarks. We show how a complicated two-dimensional pipeline-the prototypical non-data-parallel algorithm- can be constructed with ease. To demonstrate the flexibility of the library, we give examples of the stepwise, efficient parallel implementation of nonlocal boundary conditions common in aircraft simulations, as well as the construction of the sequence of grids required for multigrid.

The complete chloroplast genome sequence of strawberry (Fragaria  × ananassa Duch.) and comparison with related species of Rosaceae

PubMed Central

Cheng, Hui; Li, Jinfeng; Zhang, Hong; Cai, Binhua; Gao, Zhihong

2017-01-01

Compared with other members of the family Rosaceae, the chloroplast genomes of Fragaria species exhibit low variation, and this situation has limited phylogenetic analyses; thus, complete chloroplast genome sequencing of Fragaria species is needed. In this study, we sequenced the complete chloroplast genome of F. × ananassa ‘Benihoppe’ using the Illumina HiSeq 2500-PE150 platform and then performed a combination of de novo assembly and reference-guided mapping of contigs to generate complete chloroplast genome sequences. The chloroplast genome exhibits a typical quadripartite structure with a pair of inverted repeats (IRs, 25,936 bp) separated by large (LSC, 85,531 bp) and small (SSC, 18,146 bp) single-copy (SC) regions. The length of the F. × ananassa ‘Benihoppe’ chloroplast genome is 155,549 bp, representing the smallest Fragaria chloroplast genome observed to date. The genome encodes 112 unique genes, comprising 78 protein-coding genes, 30 tRNA genes and four rRNA genes. Comparative analysis of the overall nucleotide sequence identity among ten complete chloroplast genomes confirmed that for both coding and non-coding regions in Rosaceae, SC regions exhibit higher sequence variation than IRs. The Ka/Ks ratio of most genes was less than 1, suggesting that most genes are under purifying selection. Moreover, the mVISTA results also showed a high degree of conservation in genome structure, gene order and gene content in Fragaria, particularly among three octoploid strawberries which were F. × ananassa ‘Benihoppe’, F. chiloensis (GP33) and F. virginiana (O477). However, when the sequences of the coding and non-coding regions of F. × ananassa ‘Benihoppe’ were compared in detail with those of F. chiloensis (GP33) and F. virginiana (O477), a number of SNPs and InDels were revealed by MEGA 7. Six non-coding regions (trnK-matK, trnS-trnG, atpF-atpH, trnC-petN, trnT-psbD and trnP-psaJ) with a percentage of variable sites greater than 1% and no less than five parsimony-informative sites were identified and may be useful for phylogenetic analysis of the genus Fragaria. PMID:29038765

Not just a rural occurrence: differences in agricultural equipment crash characteristics by rural-urban crash site and proximity to town.

PubMed

Harland, Karisa K; Greenan, Mitchell; Ramirez, Marizen

2014-09-01

Although approximately one-third of agricultural equipment-related crashes occur near town, these crashes are thought to be a rural problem. This analysis examines differences between agricultural equipment-related crashes by their urban-rural distribution and distance from a town. Agricultural equipment crashes were collected from nine Midwest Departments of Transportation (2005-2008). Crash zip code was assigned as urban or rural (large, small and isolated) using Rural-Urban Commuting Areas. Crash proximity to a town was estimated with ArcGIS. Multivariable logistic regression was used to estimate the odds of crashing in an urban versus rural zip codes and across rural gradients. ANOVA analysis estimated mean distance (miles) from a crash site to a town. Over four years, 4444 crashes involved agricultural equipment. About 30% of crashes occurred in urban zip codes. Urban crashes were more likely to be non-collisions (aOR=1.69[1.24-2.30]), involve ≥2 vehicles (2 vehicles: aOR=1.58[1.14-2.20], 3+ vehicles: aOR=1.68[0.98-2.88]), occur in a town (aOR=2.06[1.73-2.45]) and within one mile of a town (aOR=1.65[1.40-1.95]) than rural crashes. The proportion of crashes within a town differed significantly across rural gradients (P<0.0001). Small rural crashes, compared to isolated rural crashes, were 1.98 (95%CI[1.28-3.06]) times more likely to be non-collisions. The distance from the crash to town differed significantly by the urban-rural distribution (P<0.0001). Crashes with agricultural equipment are unexpectedly common in urban areas and near towns and cities. Education among all roadway users, increased visibility of agricultural equipment and the development of complete rural roads are needed to increase road safety and prevent agricultural equipment-related crashes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis.

PubMed

Iorio, Andrea; De Lillo, Antonella; De Angelis, Flavio; Di Girolamo, Marco; Luigetti, Marco; Sabatelli, Mario; Pradotto, Luca; Mauro, Alessandro; Mazzeo, Anna; Stancanelli, Claudia; Perfetto, Federico; Frusconi, Sabrina; My, Filomena; Manfellotto, Dario; Fuciarelli, Maria; Polimanti, Renato

2017-09-01

Coding mutations in TTR gene cause a rare hereditary form of systemic amyloidosis, which has a complex genotype-phenotype correlation. We investigated the role of non-coding variants in regulating TTR gene expression and consequently amyloidosis symptoms. We evaluated the genotype-phenotype correlation considering the clinical information of 129 Italian patients with TTR amyloidosis. Then, we conducted a re-sequencing of TTR gene to investigate how non-coding variants affect TTR expression and, consequently, phenotypic presentation in carriers of amyloidogenic mutations. Polygenic scores for genetically determined TTR expression were constructed using data from our re-sequencing analysis and the GTEx (Genotype-Tissue Expression) project. We confirmed a strong phenotypic heterogeneity across coding mutations causing TTR amyloidosis. Considering the effects of non-coding variants on TTR expression, we identified three patient clusters with specific expression patterns associated with certain phenotypic presentations, including late onset, autonomic neurological involvement, and gastrointestinal symptoms. This study provides novel data regarding the role of non-coding variation and the gene expression profiles in patients affected by TTR amyloidosis, also putting forth an approach that could be used to investigate the mechanisms at the basis of the genotype-phenotype correlation of the disease.

Multilevel Concatenated Block Modulation Codes for the Frequency Non-selective Rayleigh Fading Channel

NASA Technical Reports Server (NTRS)

Lin, Shu; Rhee, Dojun

1996-01-01

This paper is concerned with construction of multilevel concatenated block modulation codes using a multi-level concatenation scheme for the frequency non-selective Rayleigh fading channel. In the construction of multilevel concatenated modulation code, block modulation codes are used as the inner codes. Various types of codes (block or convolutional, binary or nonbinary) are being considered as the outer codes. In particular, we focus on the special case for which Reed-Solomon (RS) codes are used as the outer codes. For this special case, a systematic algebraic technique for constructing q-level concatenated block modulation codes is proposed. Codes have been constructed for certain specific values of q and compared with the single-level concatenated block modulation codes using the same inner codes. A multilevel closest coset decoding scheme for these codes is proposed.

Small RNA deep sequencing identifies novel and salt-stress-regulated microRNAs from roots of Medicago sativa and Medicago truncatula.

PubMed

Long, Rui-Cai; Li, Ming-Na; Kang, Jun-Mei; Zhang, Tie-Jun; Sun, Yan; Yang, Qing-Chuan

2015-05-01

Small 21- to 24-nucleotide (nt) ribonucleic acids (RNAs), notably the microRNA (miRNA), are emerging as a posttranscriptional regulation mechanism. Salt stress is one of the primary abiotic stresses that cause the crop losses worldwide. In saline lands, root growth and function of plant are determined by the action of environmental salt stress through specific genes that adapt root development to the restrictive condition. To elucidate the role of miRNAs in salt stress regulation in Medicago, we used a high-throughput sequencing approach to analyze four small RNA libraries from roots of Zhongmu-1 (Medicago sativa) and Jemalong A17 (Medicago truncatula), which were treated with 300 mM NaCl for 0 and 8 h. Each library generated about 20 million short sequences and contained predominantly small RNAs of 24-nt length, followed by 21-nt and 22-nt small RNAs. Using sequence analysis, we identified 385 conserved miRNAs from 96 families, along with 68 novel candidate miRNAs. Of all the 68 predicted novel miRNAs, 15 miRNAs were identified to have miRNA*. Statistical analysis on abundance of sequencing read revealed specific miRNA showing contrasting expression patterns between M. sativa and M. truncatula roots, as well as between roots treated for 0 and 8 h. The expression of 10 conserved and novel miRNAs was also quantified by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The miRNA precursor and target genes were predicted by bioinformatics analysis. We concluded that the salt stress related conserved and novel miRNAs may have a large variety of target mRNAs, some of which might play key roles in salt stress regulation of Medicago. © 2014 Scandinavian Plant Physiology Society.

Unfiltered Talk--A Challenge to Categories.

ERIC Educational Resources Information Center

McCormick, Kay

A study investigated how and why code switching and mixing occurs between English and Afrikaans in a region of South Africa. In District Six, non-standard Afrikaans seems to be a mixed code, and it is unclear whether non-standard English is a mixed code. Consequently, it is unclear when codes are being switched or mixed. The analysis looks at…

Epigenetic Therapy in Lung Cancer – Role of microRNAs

PubMed Central

Rothschild, Sacha I.

2013-01-01

Lung cancer is the leading cause of cancer deaths worldwide. microRNAs (miRNAs) are a class of small non-coding RNA species that have been implicated in the control of many fundamental cellular and physiological processes such as cellular differentiation, proliferation, apoptosis, and stem cell maintenance. Some miRNAs have been categorized as “oncomiRs” as opposed to “tumor suppressor miRs.” This review focuses on the role of miRNAs in the lung cancer carcinogenesis and their potential as diagnostic, prognostic, or predictive markers. PMID:23802096

Results of a Research Study to Identify Historical Procurement Obligations and Expenditures on Major Army Materiel and Non-Materiel Systems,

DTIC Science & Technology

1983-05-01

release; distribution 2b. DECLASSIFICATION/DOWNGRADING SCHEDULE unlimited. 4. PERFORMING ORGANIZATION REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT...coding scheme derives from the location of the Budget Line Items in Exhibit P-1 (Supporting Data for the President’s Budget), the BLIN’s reflect the same...MULTI-PURPOSE WHEELED VEH 305046 COMMERCIAL UTILITY CARGO VEHICLE 305017 SMALL UNIT SUPPORT VEHICLE(SYSV) 30504 TRUCK ST 6X6 ABT 305019 TRUCK, iOT ,8X8,ART

Functional interrogation of non-coding DNA through CRISPR genome editing

PubMed Central

Canver, Matthew C.; Bauer, Daniel E.; Orkin, Stuart H.

2017-01-01

Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. PMID:28288828

Implementation and performance of shutterless uncooled micro-bolometer cameras

NASA Astrophysics Data System (ADS)

Das, J.; de Gaspari, D.; Cornet, P.; Deroo, P.; Vermeiren, J.; Merken, P.

2015-06-01

A shutterless algorithm is implemented into the Xenics LWIR thermal cameras and modules. Based on a calibration set and a global temperature coefficient the optimal non-uniformity correction is calculated onboard of the camera. The limited resources in the camera require a compact algorithm, hence the efficiency of the coding is important. The performance of the shutterless algorithm is studied by a comparison of the residual non-uniformity (RNU) and signal-to-noise ratio (SNR) between the shutterless and shuttered correction algorithm. From this comparison we conclude that the shutterless correction is only slightly less performant compared to the standard shuttered algorithm, making this algorithm very interesting for thermal infrared applications where small weight and size, and continuous operation are important.

miRNAs as therapeutic targets in ischemic heart disease.

PubMed

Frost, Robert J A; van Rooij, Eva

2010-06-01

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

Interplay between cardiac transcription factors and non-coding RNAs in predisposing to atrial fibrillation.

PubMed

Mikhailov, Alexander T; Torrado, Mario

2018-05-12

There is growing evidence that putative gene regulatory networks including cardio-enriched transcription factors, such as PITX2, TBX5, ZFHX3, and SHOX2, and their effector/target genes along with downstream non-coding RNAs can play a potentially important role in the process of adaptive and maladaptive atrial rhythm remodeling. In turn, expression of atrial fibrillation-associated transcription factors is under the control of upstream regulatory non-coding RNAs. This review broadly explores gene regulatory mechanisms associated with susceptibility to atrial fibrillation-with key examples from both animal models and patients-within the context of both cardiac transcription factors and non-coding RNAs. These two systems appear to have multiple levels of cross-regulation and act coordinately to achieve effective control of atrial rhythm effector gene expression. Perturbations of a dynamic expression balance between transcription factors and corresponding non-coding RNAs can provoke the development or promote the progression of atrial fibrillation. We also outline deficiencies in current models and discuss ongoing studies to clarify remaining mechanistic questions. An understanding of the function of transcription factors and non-coding RNAs in gene regulatory networks associated with atrial fibrillation risk will enable the development of innovative therapeutic strategies.

Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules.

PubMed

Childs-Disney, Jessica L; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z; Hoskins, Jason; Southall, Noel; Marugan, Juan J; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P; Schatz, George C; Sobczak, Krzysztof; Thornton, Charles A; Disney, Matthew D

2013-01-01

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)(exp)). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. A thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)(exp) and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)(exp). This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)(exp) and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of myotonic dystrophy type 1.

Induction and Reversal of Myotonic Dystrophy Type 1 Pre-mRNA Splicing Defects by Small Molecules

PubMed Central

Childs-Disney, Jessica L.; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z.; Hoskins, Jason; Southall, Noel; Marugan, Juan J.; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P.; Schatz, George C.; Sobczak, Krzysztof; Thornton, Charles A.; Disney, Matthew D.

2013-01-01

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 (DM1) is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)exp). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. The thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)exp and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)exp. This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)exp and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of DM1. PMID:23806903

A mixture of sparse coding models explaining properties of face neurons related to holistic and parts-based processing

PubMed Central

2017-01-01

Experimental studies have revealed evidence of both parts-based and holistic representations of objects and faces in the primate visual system. However, it is still a mystery how such seemingly contradictory types of processing can coexist within a single system. Here, we propose a novel theory called mixture of sparse coding models, inspired by the formation of category-specific subregions in the inferotemporal (IT) cortex. We developed a hierarchical network that constructed a mixture of two sparse coding submodels on top of a simple Gabor analysis. The submodels were each trained with face or non-face object images, which resulted in separate representations of facial parts and object parts. Importantly, evoked neural activities were modeled by Bayesian inference, which had a top-down explaining-away effect that enabled recognition of an individual part to depend strongly on the category of the whole input. We show that this explaining-away effect was indeed crucial for the units in the face submodel to exhibit significant selectivity to face images over object images in a similar way to actual face-selective neurons in the macaque IT cortex. Furthermore, the model explained, qualitatively and quantitatively, several tuning properties to facial features found in the middle patch of face processing in IT as documented by Freiwald, Tsao, and Livingstone (2009). These included, in particular, tuning to only a small number of facial features that were often related to geometrically large parts like face outline and hair, preference and anti-preference of extreme facial features (e.g., very large/small inter-eye distance), and reduction of the gain of feature tuning for partial face stimuli compared to whole face stimuli. Thus, we hypothesize that the coding principle of facial features in the middle patch of face processing in the macaque IT cortex may be closely related to mixture of sparse coding models. PMID:28742816

A mixture of sparse coding models explaining properties of face neurons related to holistic and parts-based processing.

PubMed

Hosoya, Haruo; Hyvärinen, Aapo

2017-07-01

Experimental studies have revealed evidence of both parts-based and holistic representations of objects and faces in the primate visual system. However, it is still a mystery how such seemingly contradictory types of processing can coexist within a single system. Here, we propose a novel theory called mixture of sparse coding models, inspired by the formation of category-specific subregions in the inferotemporal (IT) cortex. We developed a hierarchical network that constructed a mixture of two sparse coding submodels on top of a simple Gabor analysis. The submodels were each trained with face or non-face object images, which resulted in separate representations of facial parts and object parts. Importantly, evoked neural activities were modeled by Bayesian inference, which had a top-down explaining-away effect that enabled recognition of an individual part to depend strongly on the category of the whole input. We show that this explaining-away effect was indeed crucial for the units in the face submodel to exhibit significant selectivity to face images over object images in a similar way to actual face-selective neurons in the macaque IT cortex. Furthermore, the model explained, qualitatively and quantitatively, several tuning properties to facial features found in the middle patch of face processing in IT as documented by Freiwald, Tsao, and Livingstone (2009). These included, in particular, tuning to only a small number of facial features that were often related to geometrically large parts like face outline and hair, preference and anti-preference of extreme facial features (e.g., very large/small inter-eye distance), and reduction of the gain of feature tuning for partial face stimuli compared to whole face stimuli. Thus, we hypothesize that the coding principle of facial features in the middle patch of face processing in the macaque IT cortex may be closely related to mixture of sparse coding models.

Crosstalk between Long Noncoding RNAs and MicroRNAs in Health and Disease.

PubMed

Bayoumi, Ahmed S; Sayed, Amer; Broskova, Zuzana; Teoh, Jian-Peng; Wilson, James; Su, Huabo; Tang, Yao-Liang; Kim, Il-Man

2016-03-11

Protein-coding genes account for only a small part of the human genome; in fact, the vast majority of transcripts are comprised of non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs) and small ncRNAs, microRNAs (miRs). Accumulating evidence indicates that ncRNAs could play critical roles in regulating many cellular processes which are often implicated in health and disease. For example, ncRNAs are aberrantly expressed in cancers, heart diseases, and many other diseases. LncRNAs and miRs are therefore novel and promising targets to be developed into biomarkers for diagnosis and prognosis as well as treatment options. The interaction between lncRNAs and miRs as well as its pathophysiological significance have recently been reported. Mechanistically, it is believed that lncRNAs exert "sponge-like" effects on various miRs, which subsequently inhibits miR-mediated functions. This crosstalk between two types of ncRNAs frequently contributes to the pathogenesis of the disease. In this review, we provide a summary of the recent studies highlighting the interaction between these ncRNAs and the effects of this interaction on disease pathogenesis and regulation.

Crosstalk between Long Noncoding RNAs and MicroRNAs in Health and Disease

PubMed Central

Bayoumi, Ahmed S.; Sayed, Amer; Broskova, Zuzana; Teoh, Jian-Peng; Wilson, James; Su, Huabo; Tang, Yao-Liang; Kim, Il-man

2016-01-01

Protein-coding genes account for only a small part of the human genome; in fact, the vast majority of transcripts are comprised of non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs) and small ncRNAs, microRNAs (miRs). Accumulating evidence indicates that ncRNAs could play critical roles in regulating many cellular processes which are often implicated in health and disease. For example, ncRNAs are aberrantly expressed in cancers, heart diseases, and many other diseases. LncRNAs and miRs are therefore novel and promising targets to be developed into biomarkers for diagnosis and prognosis as well as treatment options. The interaction between lncRNAs and miRs as well as its pathophysiological significance have recently been reported. Mechanistically, it is believed that lncRNAs exert “sponge-like” effects on various miRs, which subsequently inhibits miR-mediated functions. This crosstalk between two types of ncRNAs frequently contributes to the pathogenesis of the disease. In this review, we provide a summary of the recent studies highlighting the interaction between these ncRNAs and the effects of this interaction on disease pathogenesis and regulation. PMID:26978351

A METABOLITE OF METHOXYCHLOR,2,2-BIS(P-HYDOXYPHENYL)-1,1,1- TRICHLOROETHANE REDUCES TESTOSTERONE BIOSYNTHESIS IN RAT LEYDIG CELLS THROUGH SUPPRESSION OF STEADY-STATE MESSENGER RIBONUCLEIC ACID LEVELS OF THE CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME

EPA Science Inventory

Postnatal development of Leydig cells involves transformation through three stages: progenitor, immature, and adult Leydig cells. The process of differentiation is accompanied by a progressive increase in the capacity of Leydig cells to produce testosterone (T). T promotes the ma...

The Meduza experiment: An orbital complex ten weeks in flight

NASA Technical Reports Server (NTRS)

Ovcharov, V.

1979-01-01

The newspaper article discusses the contribution of space research to understanding the origin of life on Earth. Part of this basic research involves studying amino acids, ribonucleic acid and DNA molecules subjected to cosmic radiation. The results from the Meduza experiment are not all analyzed as yet. The article also discusses the psychological changes in cosmonauts as evidenced by their attitude towards biology experiments in space.

Human health and ecological risk assessments for SmartStax PRO (MON 89034 x TC1507 x MON 87411 x DAS-59122-7), a plant-incorporated protectant intended to control corn rootworm through ribonucleic acid (RNA) interference

EPA Science Inventory

The use of RNA interference (RNAi) gene silencing technology, particularly RNAi for pesticidal purposes to control macroorganism pests, is a relatively recent innovation. Post-transcriptional silencing of gene function is a very rapid process where double-stranded RNA (dsRNA) dir...

Fine-structure mapping of the firA gene, a locus involved in the phenotypic expression of rifampin resistance in Escherichia.

PubMed

Lathe, R

1977-09-01

The firA (Ts)200 mutation not only eliminates the resistance to rifampin of certain genetically resistant strains, but, moreover, renders ribonucleic acid synthesis thermolabile. The firA gene has been mapped by P1 tranduction and is located extremely close to the structural gene for deoxyribonucleic acid polymerase III at 4 min on the Escherichia coli linkage map.

Interferon Action on Parental Semliki Forest Virus Ribonucleic Acid

PubMed Central

Friedman, Robert M.; Fantes, Karl H.; Levy, Hilton B.; Carter, William B.

1967-01-01

Actinomycin D-treated chick fibroblasts were infected with purified 32P-labeled Semliki forest virus, and ribonucleic acid (RNA) was extracted after 1 or 2 hr. Within 1 hr, viral RNA forms sedimenting in sucrose gradients at 42S, 30S, and 16S were present. The 42S form corresponded to the RNA of the virion. The 16S form appeared to be a double-stranded template for the formation of new viral RNA, since nascent RNA was associated with it and the molecule could be heat-denatured and subsequently reannealed by slow cooling. Interferon treatment before infection, or puromycin (50 μg/ml) or cycloheximide (200 μg/ml) added at the time of virus infection, had no effect on the formation of the 30S RNA but inhibited the production of the 16S form. Several findings made it unlikely that these results were due to breakdown of parental RNA and reincorporation of 32P into progeny structures. The results suggested that the mechanism of interferon action involves inhibition of protein synthesis by parental viral RNA, since a specific viral RNA polymerase had previously been demonstrated to be necessary for production of 16S RNA. No protein synthesis appears necessary for formation of 30S RNA from parental virus RNA. PMID:5621488

Dietary ribonucleic acid suppresses inflammation of adipose tissue and improves glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high-fat diet.

PubMed

Sakai, Tohru; Taki, Tomoyo; Nakamoto, Akiko; Tazaki, Shiho; Arakawa, Mai; Nakamoto, Mariko; Tsutsumi, Rie; Shuto, Emi

2015-01-01

Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.

Label-free serum ribonucleic acid analysis for colorectal cancer detection by surface-enhanced Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Chen, Yanping; Chen, Gang; Feng, Shangyuan; Pan, Jianji; Zheng, Xiongwei; Su, Ying; Chen, Yan; Huang, Zufang; Lin, Xiaoqian; Lan, Fenghua; Chen, Rong; Zeng, Haishan

2012-06-01

Studies with circulating ribonucleic acid (RNA) not only provide new targets for cancer detection, but also open up the possibility of noninvasive gene expression profiling for cancer. In this paper, we developed a surface-enhanced Raman scattering (SERS), platform for detection and differentiation of serum RNAs of colorectal cancer. A novel three-dimensional (3-D), Ag nanofilm formed by dry MgSO4 aggregated silver nanoparticles, Ag NP, as the SERS-active substrate was presented to effectively enhance the RNA Raman signals. SERS measurements were performed on two groups of serum RNA samples. One group from patients, n=55 with pathologically diagnosed colorectal cancer and the other group from healthy controls, n=45. Tentative assignments of the Raman bands in the normalized SERS spectra demonstrated that there are differential expressions of cancer-related RNAs between the two groups. Linear discriminate analysis, based on principal component analysis, generated features can differentiate the colorectal cancer SERS spectra from normal SERS spectra with sensitivity of 89.1 percent and specificity of 95.6 percent. This exploratory study demonstrated great potential for developing serum RNA SERS analysis into a useful clinical tool for label-free, noninvasive screening and detection of colorectal cancers.

TNF-α messenger ribonucleic acid (mRNA) in patients with nonalcoholic steatohepatitis.

PubMed

Alaaeddine, Nada; Sidaoui, Joseph; Hilal, George; Serhal, Reem; Abedelrahman, Abir; Khoury, Salem

2012-01-01

tumor necrosis factor (TNF)-α plays a significant role in the pathogenesis of nonalcoholic steatohepatitis (NASH). A few studies have confirmed high TNF-α plasma protein levels in patients with NASH compared to healthy volunteers. We herein aimed to revisit these findings using other molecular techniques. a cross-sectional evaluation of patients newly diagnosed with NASH. A quantitative assay for the measurement of TNF-α messenger ribonucleic acid (mRNA) was performed for NASH patients and controls using real-time reverse transcription polymerase chain reaction (RT-PCR). in 39 patients with NASH (mean age 38.6 ± 9.4 years, range 28-60 years; 79% males), the mean TNF-α mRNA level was significantly higher than that found for controls (137.6 ± 102.3 ng/mL versus 83.5 ± 43.8 ng/mL, respectively; P = 0.012). A TNF-α mRNA cut-off of 100 ng/mL predicted NASH most optimally (AUC 0.685 ± 0.066, P = 0.01; with 66.7% sensitivity and 74.1% specificity). Serum TNF-α and soluble TNF-α receptor II (sTNFRII) levels were significantly higher in patients compared to controls using ELISA. high TNF-α mRNA levels, determined by RT-PCR, characterize patients with NASH.

Small nucleolar RNAs that guide modification in trypanosomatids: repertoire, targets, genome organisation, and unique functions.

PubMed

Uliel, Shai; Liang, Xue-hai; Unger, Ron; Michaeli, Shulamit

2004-03-29

Small nucleolar RNAs constitute a family of newly discovered non-coding small RNAs, most of which function in guiding RNA modifications. Two prevalent types of modifications are 2'-O-methylation and pseudouridylation. The modification is directed by the formation of a canonical small nucleolar RNA-target duplex. Initially, RNA-guided modification was shown to take place on rRNA, but recent studies suggest that small nuclear RNA, mRNA, tRNA, and the trypanosome spliced leader RNA also undergo guided modifications. Trypanosomes contain more modifications and potentially more small nucleolar RNAs than yeast, and the increased number of modifications may help to preserve ribosome function under adverse environmental conditions during the cycling between the insect and mammalian host. The genome organisation in clusters carrying the two types of small nucleolar RNAs, C/D and H/ACA-like RNAs, resembles that in plants. However, the trypanosomatid H/ACA RNAs are similar to those found in Archaea and are composed of a single hairpin that may represent the primordial H/ACA RNA. In this review we summarise this new field of trypanosome small nucleolar RNAs, emphasising the open questions regarding the number of small nucleolar RNAs, the repertoire, genome organisation, and the unique function of guided modifications in these protozoan parasites.

Role of miRNAs and siRNAs in biotic and abiotic stress responses of plants

PubMed Central

Khraiwesh, Basel; Zhu, Jian-Kang; Zhu, Jianhua

2011-01-01

Small, non-coding RNAs are a distinct class of regulatory RNAs in plants and animals that control a variety of biological processes. In plants, several classes of small RNAs with specific sizes and dedicated functions have evolved through a series of pathways. The major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis. miRNAs control the expression of cognate target genes by binding to reverse complementary sequences, resulting in cleavage or translational inhibition of the target RNAs. siRNAs have a similar structure, function, and biogenesis as miRNAs but are derived from long double-stranded RNAs and can often direct DNA methylation at target sequences. Besides their roles in growth and development and maintenance of genome integrity, small RNAs are also important components in plant stress responses. One way in which plants respond to environmental stress is by modifying their gene expression through the activity of small RNAs. Thus, understanding how small RNAs regulate gene expression will enable researchers to explore the role of small RNAs in biotic and abiotic stress responses. This review focuses on the regulatory roles of plant small RNAs in the adaptive response to stresses. PMID:21605713

Design of ACM system based on non-greedy punctured LDPC codes

NASA Astrophysics Data System (ADS)

Lu, Zijun; Jiang, Zihong; Zhou, Lin; He, Yucheng

2017-08-01

In this paper, an adaptive coded modulation (ACM) scheme based on rate-compatible LDPC (RC-LDPC) codes was designed. The RC-LDPC codes were constructed by a non-greedy puncturing method which showed good performance in high code rate region. Moreover, the incremental redundancy scheme of LDPC-based ACM system over AWGN channel was proposed. By this scheme, code rates vary from 2/3 to 5/6 and the complication of the ACM system is lowered. Simulations show that more and more obvious coding gain can be obtained by the proposed ACM system with higher throughput.

What Is New in the miRNA World Regarding Osteosarcoma and Chondrosarcoma?

PubMed

Palmini, Gaia; Marini, Francesca; Brandi, Maria Luisa

2017-03-07

Despite the availability of multimodal and aggressive therapies, currently patients with skeletal sarcomas, including osteosarcoma and chondrosarcoma, often have a poor prognosis. In recent decades, advances in sequencing technology have revealed the presence of RNAs without coding potential known as non-coding RNAs (ncRNAs), which provides evidence that protein-coding genes account for only a small percentage of the entire genome. This has suggested the influence of ncRNAs during development, apoptosis and cell proliferation. The discovery of microRNAs (miRNAs) in 1993 underscored the importance of these molecules in pathological diseases such as cancer. Increasing interest in this field has allowed researchers to study the role of miRNAs in cancer progression. Regarding skeletal sarcomas, the research surrounding which miRNAs are involved in the tumourigenesis of osteosarcoma and chondrosarcoma has rapidly gained traction, including the identification of which miRNAs act as tumour suppressors and which act as oncogenes. In this review, we will summarize what is new regarding the roles of miRNAs in chondrosarcoma as well as the latest discoveries of identified miRNAs in osteosarcoma.

Identification of coding and non-coding mutational hotspots in cancer genomes.

PubMed

Piraino, Scott W; Furney, Simon J

2017-01-05

The identification of mutations that play a causal role in tumour development, so called "driver" mutations, is of critical importance for understanding how cancers form and how they might be treated. Several large cancer sequencing projects have identified genes that are recurrently mutated in cancer patients, suggesting a role in tumourigenesis. While the landscape of coding drivers has been extensively studied and many of the most prominent driver genes are well characterised, comparatively less is known about the role of mutations in the non-coding regions of the genome in cancer development. The continuing fall in genome sequencing costs has resulted in a concomitant increase in the number of cancer whole genome sequences being produced, facilitating systematic interrogation of both the coding and non-coding regions of cancer genomes. To examine the mutational landscapes of tumour genomes we have developed a novel method to identify mutational hotspots in tumour genomes using both mutational data and information on evolutionary conservation. We have applied our methodology to over 1300 whole cancer genomes and show that it identifies prominent coding and non-coding regions that are known or highly suspected to play a role in cancer. Importantly, we applied our method to the entire genome, rather than relying on predefined annotations (e.g. promoter regions) and we highlight recurrently mutated regions that may have resulted from increased exposure to mutational processes rather than selection, some of which have been identified previously as targets of selection. Finally, we implicate several pan-cancer and cancer-specific candidate non-coding regions, which could be involved in tumourigenesis. We have developed a framework to identify mutational hotspots in cancer genomes, which is applicable to the entire genome. This framework identifies known and novel coding and non-coding mutional hotspots and can be used to differentiate candidate driver regions from likely passenger regions susceptible to somatic mutation.

Partial purification, characterization and translation in vitro of rat liver metallothionein messenger ribonucleic acid.

PubMed Central

Andersen, R D; Weser, U

1978-01-01

Poly(A)+ (polyadenylated) mRNA coding for metallothioneins was purified 13-fold from rat liver polyribosomes and was identified by its ability to direct the biosynthesis of these proteins in a wheat-germ cell-free system. The carboxymethylated products of the protein-synthesizing system in vitro were analysed with sodium dodecyl sulphate/20% polyacrylamide-gel electrophoresis. The labelled compounds [3H]serine and [35S]cysteine were incorporated at high specific radioactivity into proteins that co-migrated with authentic metallothioneins. No [3H]leucine incorporation was found, in agreement with the amino acid composition of the metallothioneins. Metallothionein mRNA had a sedimentation coefficient of 9 S and carried a maximum of four ribosomes. At 5 h after a subcutaneous injection of ZnCl2 or CdCl2 (10 mumol/kg body wt.), the amount of this mRNA increased approx. 2- and 4-fold respectively, on the basis of translation in vitro. The increase in metallothionein mRNA (defined by translation in the wheat-germ system) was transient and, after CdCl2 treatment, fell back to control values by 17 h. Metallothioneins constituted a maximum of 0.8% of the total protein products synthesized in the wheat-germ system by total mRNA isolated from rat liver after CdCl2 treatment. Images Fig. 5. Fig. 6. PMID:743237

Non-coding, mRNA-like RNAs database Y2K.

PubMed

Erdmann, V A; Szymanski, M; Hochberg, A; Groot, N; Barciszewski, J

2000-01-01

In last few years much data has accumulated on various non-translatable RNA transcripts that are synthesised in different cells. They are lacking in protein coding capacity and it seems that they work mainly or exclusively at the RNA level. All known non-coding RNA transcripts are collected in the database: http://www. man.poznan.pl/5SData/ncRNA/index.html

Non-coding, mRNA-like RNAs database Y2K

PubMed Central

Erdmann, Volker A.; Szymanski, Maciej; Hochberg, Abraham; Groot, Nathan de; Barciszewski, Jan

2000-01-01

In last few years much data has accumulated on various non-translatable RNA transcripts that are synthesised in different cells. They are lacking in protein coding capacity and it seems that they work mainly or exclusively at the RNA level. All known non-coding RNA transcripts are collected in the database: http://www.man.poznan.pl/5SData/ncRNA/index.html PMID:10592224

13 CFR 121.1103 - What are the procedures for appealing a NAICS code designation?

Code of Federal Regulations, 2010 CFR

2010-01-01

... appealing a NAICS code designation? 121.1103 Section 121.1103 Business Credit and Assistance SMALL BUSINESS... Determinations and Naics Code Designations § 121.1103 What are the procedures for appealing a NAICS code... code designation and applicable size standard must be served and filed within 10 calendar days after...

Functional interrogation of non-coding DNA through CRISPR genome editing.

PubMed

Canver, Matthew C; Bauer, Daniel E; Orkin, Stuart H

2017-05-15

Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the capability of the PCV2 genome to encode miRNAs: lack of viral miRNA expression in an experimental infection.

PubMed

Núñez-Hernández, Fernando; Pérez, Lester J; Vera, Gonzalo; Córdoba, Sarai; Segalés, Joaquim; Sánchez, Armand; Núñez, José I

2015-05-01

Porcine circovirus type 2 (PCV2) is a ssDNA virus causing PCV2-systemic disease (PCV2-SD), one of the most important diseases in swine. MicroRNAs (miRNAs) are a new class of small non-coding RNAs that regulate gene expression post-transcriptionally. Viral miRNAs have recently been described and the number of viral miRNAs has been increasing in the past few years. In this study, small RNA libraries were constructed from two tissues of subclinically PCV2 infected pigs to explore if PCV2 can encode viral miRNAs. The deep sequencing data revealed that PCV2 does not express miRNAs in an in vivo subclinical infection.

Non-axisymmetric line-driven disc winds - I. Disc perturbations

NASA Astrophysics Data System (ADS)

Dyda, Sergei; Proga, Daniel

2018-04-01

We study mass outflows driven from accretion discs by radiation pressure due to spectral lines. To investigate non-axisymmetric effects, we use the ATHENA++ code and develop a new module to account for radiation pressure driving. In 2D, our new simulations are consistent with previous 2D axisymmetric solutions by Proga et al., who used the ZEUS 2D code. Specifically, we find that the disc winds are time dependent, characterized by a dense stream confined to ˜45° relative to the disc mid-plane and bounded on the polar side by a less dense, fast stream. In 3D, we introduce a vertical, ϕ-dependent, subsonic velocity perturbation in the disc mid-plane. The perturbation does not change the overall character of the solution but global outflow properties such as the mass, momentum, and kinetic energy fluxes are altered by up to 100 per cent. Non-axisymmetric density structures develop and persist mainly at the base of the wind. They are relatively small, and their densities can be a few times higher than the azimuthal average. The structure of the non-axisymmetric and axisymmetric solutions differ also in other ways. Perhaps most importantly from the observational point of view are the differences in the so-called clumping factors, that serve as a proxy for emissivity due to two body processes. In particular, the spatially averaged clumping factor over the entire fast stream, while it is of a comparable value in both solutions, it varies about 10 times faster in the non-axisymmetric case.

Integrating non-coding RNAs in JAK-STAT regulatory networks

PubMed Central

Witte, Steven; Muljo, Stefan A

2014-01-01

Being a well-characterized pathway, JAK-STAT signaling serves as a valuable paradigm for studying the architecture of gene regulatory networks. The discovery of untranslated or non-coding RNAs, namely microRNAs and long non-coding RNAs, provides an opportunity to elucidate their roles in such networks. In principle, these regulatory RNAs can act as downstream effectors of the JAK-STAT pathway and/or affect signaling by regulating the expression of JAK-STAT components. Examples of interactions between signaling pathways and non-coding RNAs have already emerged in basic cell biology and human diseases such as cancer, and can potentially guide the identification of novel biomarkers or drug targets for medicine. PMID:24778925

76 FR 38160 - Pesticide Products; Registration Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

.... Potentially affected entities may include, but are not limited to: Crop production (NAICS code 111). Animal production (NAICS code 112). Food manufacturing (NAICS code 311). Pesticide manufacturing (NAICS code 32532... classification/Use: For control of certain diseases in almond, grape (small fruit vine climbing group, except...

75 FR 9141 - Reduced 2009 Estimated Income Tax Payments for Individuals With Small Business Income

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... Reduced 2009 Estimated Income Tax Payments for Individuals With Small Business Income AGENCY: Internal... their required 2009 estimated income tax payments. The temporary regulations implement section 1212 of... Revenue Code (Code) to provide for reduced 2009 estimated income tax payments for certain qualified...

Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway

PubMed Central

He, Jin-Lian; Zhou, Zhi-Wei; Yin, Juan-Juan; He, Chang-Qiang; Zhou, Shu-Feng; Yu, Yang

2015-01-01

Drug metabolizing enzymes (DMEs) and drug transporters are regulated via epigenetic, transcriptional, posttranscriptional, and translational and posttranslational modifications. Phase I and II DMEs and drug transporters play an important role in the disposition and detoxification of a large number of endogenous and exogenous compounds. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a critical regulator of a variety of important cytoprotective genes that are involved in disposition and detoxification of xenobiotics. Schisandra chinensis (SC) is a commonly used traditional Chinese herbal medicine that has been primarily used to protect the liver because of its potent antioxidative and anti-inflammatory activities. SC can modulate some DMEs and drug transporters, but the underlying mechanisms are unclear. In this study, we aimed to explore the role of Nrf2 in the regulatory effect of SC extract (SCE) on selected DMEs and drug transporters in human hepatocellular liver carcinoma cell line (HepG2) cells. The results showed that SCE, schisandrin A, and schisandrin B significantly increased the expression of NAD(P)H: Nicotinamide Adenine Dinucleotide Phosphate-oxidase or:quinone oxidoreductase 1, heme oxygenase-1, glutamate–cysteine ligase, and glutathione S-transferase A4 at both transcriptional and posttranscriptional levels. Incubation of HepG2 cells with SCE resulted in a significant increase in the intracellular level of glutathione and total glutathione S-transferase content. SCE significantly elevated the messenger ribonucleic acid and protein levels of P-glycoprotein and multidrug resistance-associated protein 2 and 4, whereas the expression of organic anion transporting peptide 1A2 and 1B1 was significantly downregulated by SCE. Knockdown of Nrf2 by small interfering ribonucleic acid attenuated the regulatory effect of SCE on these DMEs and drug transporters. SCE significantly upregulated Nrf2 and promoted the translocation of Nrf2 from cytoplasm to the nuclei. Additionally, SCE significantly suppressed the expression of cytosolic Kelch-like ECH-associated protein 1 (the repressor of Nrf2) and remarkably increased Nrf2 stability in HepG2 cells. Taken together, our findings suggest that the hepatoprotective effects of SCE may be partially ascribed to the modulation of DMEs and drug transporters via Nrf2-mediated signaling pathway. SCE may alter the pharmacokinetics of other coadministered drugs that are substrates of these DMEs and transporters and thus cause unfavorable herb–drug interactions. PMID:25552902

An emulator for minimizing computer resources for finite element analysis

NASA Technical Reports Server (NTRS)

Melosh, R.; Utku, S.; Islam, M.; Salama, M.

1984-01-01

A computer code, SCOPE, has been developed for predicting the computer resources required for a given analysis code, computer hardware, and structural problem. The cost of running the code is a small fraction (about 3 percent) of the cost of performing the actual analysis. However, its accuracy in predicting the CPU and I/O resources depends intrinsically on the accuracy of calibration data that must be developed once for the computer hardware and the finite element analysis code of interest. Testing of the SCOPE code on the AMDAHL 470 V/8 computer and the ELAS finite element analysis program indicated small I/O errors (3.2 percent), larger CPU errors (17.8 percent), and negligible total errors (1.5 percent).

RY-Coding and Non-Homogeneous Models Can Ameliorate the Maximum-Likelihood Inferences From Nucleotide Sequence Data with Parallel Compositional Heterogeneity.

PubMed

Ishikawa, Sohta A; Inagaki, Yuji; Hashimoto, Tetsuo

2012-01-01

In phylogenetic analyses of nucleotide sequences, 'homogeneous' substitution models, which assume the stationarity of base composition across a tree, are widely used, albeit individual sequences may bear distinctive base frequencies. In the worst-case scenario, a homogeneous model-based analysis can yield an artifactual union of two distantly related sequences that achieved similar base frequencies in parallel. Such potential difficulty can be countered by two approaches, 'RY-coding' and 'non-homogeneous' models. The former approach converts four bases into purine and pyrimidine to normalize base frequencies across a tree, while the heterogeneity in base frequency is explicitly incorporated in the latter approach. The two approaches have been applied to real-world sequence data; however, their basic properties have not been fully examined by pioneering simulation studies. Here, we assessed the performances of the maximum-likelihood analyses incorporating RY-coding and a non-homogeneous model (RY-coding and non-homogeneous analyses) on simulated data with parallel convergence to similar base composition. Both RY-coding and non-homogeneous analyses showed superior performances compared with homogeneous model-based analyses. Curiously, the performance of RY-coding analysis appeared to be significantly affected by a setting of the substitution process for sequence simulation relative to that of non-homogeneous analysis. The performance of a non-homogeneous analysis was also validated by analyzing a real-world sequence data set with significant base heterogeneity.

Long Non-Coding RNAs (lncRNAs) of Sea Cucumber: Large-Scale Prediction, Expression Profiling, Non-Coding Network Construction, and lncRNA-microRNA-Gene Interaction Analysis of lncRNAs in Apostichopus japonicus and Holothuria glaberrima During LPS Challenge and Radial Organ Complex Regeneration.

PubMed

Mu, Chuang; Wang, Ruijia; Li, Tianqi; Li, Yuqiang; Tian, Meilin; Jiao, Wenqian; Huang, Xiaoting; Zhang, Lingling; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

2016-08-01

Long non-coding RNA (lncRNA) structurally resembles mRNA but cannot be translated into protein. Although the systematic identification and characterization of lncRNAs have been increasingly reported in model species, information concerning non-model species is still lacking. Here, we report the first systematic identification and characterization of lncRNAs in two sea cucumber species: (1) Apostichopus japonicus during lipopolysaccharide (LPS) challenge and in heathy tissues and (2) Holothuria glaberrima during radial organ complex regeneration, using RNA-seq datasets and bioinformatics analysis. We identified A. japonicus and H. glaberrima lncRNAs that were differentially expressed during LPS challenge and radial organ complex regeneration, respectively. Notably, the predicted lncRNA-microRNA-gene trinities revealed that, in addition to targeting protein-coding transcripts, miRNAs might also target lncRNAs, thereby participating in a potential novel layer of regulatory interactions among non-coding RNA classes in echinoderms. Furthermore, the constructed coding-non-coding network implied the potential involvement of lncRNA-gene interactions during the regulation of several important genes (e.g., Toll-like receptor 1 [TLR1] and transglutaminase-1 [TGM1]) in response to LPS challenge and radial organ complex regeneration in sea cucumbers. Overall, this pioneer systematic identification, annotation, and characterization of lncRNAs in echinoderm pave the way for similar studies and future genetic, genomic, and evolutionary research in non-model species.

The psychology of elite cycling: a systematic review.

PubMed

Spindler, David J; Allen, Mark S; Vella, Stewart A; Swann, Christian

2018-09-01

This systematic review sought to synthesise what is currently known about the psychology of elite cycling. Nine electronic databases were searched in March 2017 for studies reporting an empirical test of any psychological construct in an elite cycling sample. Fourteen studies (total n = 427) met inclusion criteria. Eight studies were coded as having high risk of bias. Themes extracted included mood, anxiety, self-confidence, pain, and cognitive function. Few studies had similar objectives meaning that in many instances findings could not be synthesised in a meaningful way. Nevertheless, there was some cross-study evidence that elite cyclists have more positive mood states (relative to normative scores), pre-race anxiety impairs performance (among male cyclists), and associative strategies are perceived as helpful for pain management. Among single studies coded as having low risk of bias, evidence suggests that implicit beliefs affect decision making performance, elite cyclists are less susceptible to mental fatigue (than non-elite cyclists), and better leadership skills relates to greater social labouring. Limitations include non-standardisation of measures, lack of follow-up data, small sample sizes, and overall poor research quality. The findings of this systematic review might be used to inform research and theory development on the psychology of elite endurance cycling.

Chromatin-bound RNA and the neurobiology of psychiatric disease.

PubMed

Tushir, J S; Akbarian, S

2014-04-04

A large, and still rapidly expanding literature on epigenetic regulation in the nervous system has provided fundamental insights into the dynamic regulation of DNA methylation and post-translational histone modifications in the context of neuronal plasticity in health and disease. Remarkably, however, very little is known about the potential role of chromatin-bound RNAs, including many long non-coding transcripts and various types of small RNAs. Here, we provide an overview on RNA-mediated regulation of chromatin structure and function, with focus on histone lysine methylation and psychiatric disease. Examples of recently discovered chromatin-bound long non-coding RNAs important for neuronal health and function include the brain-derived neurotrophic factor antisense transcript (Bdnf-AS) which regulates expression of the corresponding sense transcript, and LOC389023 which is associated with human-specific histone methylation signatures at the chromosome 2q14.1 neurodevelopmental risk locus by regulating expression of DPP10, an auxillary subunit for voltage-gated K(+) channels. We predict that the exploration of chromatin-bound RNA will significantly advance our current knowledge base in neuroepigenetics and biological psychiatry. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

75 FR 32519 - Small Business Size Standards: Waiver of the Nonmanufacturer Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... (Compressed and Liquefied Gases), under NAICS code 325120 (Industrial Gases Manufacturing). On March 23, 2010...), under NAICS code 325120 (Industrial Gases Manufacturing). Dated: June 1, 2010. Karen Hontz, Director... Propane Gas (LPG), North American Industry Classification System (NAICS) code 325120, Product Service Code...

Compliance with self-regulation of television food and beverage advertising aimed at children in Spain.

PubMed

Romero-Fernández, Ma Mar; Royo-Bordonada, Miguel Angel; Rodríguez-Artalejo, Fernando

2010-07-01

To evaluate the level of compliance with the PAOS Code (Publicidad, Actividad, Obesidad y Salud), which establishes standards for the self-regulation of food marketing aimed at minors, in television advertising by food and beverage companies that have agreed to abide by the Code. The study sample consisted of food and beverage advertisements targeting children during 80 h of programming by four Spanish television networks. The level of compliance with each standard of the PAOS Code was classified into three categories: 'compliance', 'non-compliance' and 'uncertain compliance'. Overall, an advertisement was considered compliant with the PAOS Code if it met all the standards; non-compliant if it contravened one or more standards; and uncertain in all other cases. Of a total of 203 television advertisements from companies that agreed to the PAOS Code, the overall prevalence of non-compliance was 49.3% (v. 50.8% among those that did not agree to the code), with 20.7% of advertisements considered of uncertain compliance. Non-compliance was more frequent on Saturdays, in longer advertisements, in advertisements containing promotions or dairy products, and for advertisements from companies of French or US origin. Non-compliance with the PAOS Code was very high and was similar for companies that did and did not agree to the Code, casting doubt on the Code's effectiveness and oversight system. It seems the time has come to commit to statutory regulations that reduce the negative impact of advertising on children's diets, as demanded by public health experts and consumer associations.

Nucleotide sequence determination of guinea-pig casein B mRNA reveals homology with bovine and rat alpha s1 caseins and conservation of the non-coding regions of the mRNA.

PubMed Central

Hall, L; Laird, J E; Craig, R K

1984-01-01

Nucleotide sequence analysis of cloned guinea-pig casein B cDNA sequences has identified two casein B variants related to the bovine and rat alpha s1 caseins. Amino acid homology was largely confined to the known bovine or predicted rat phosphorylation sites and within the 'signal' precursor sequence. Comparison of the deduced nucleotide sequence of the guinea-pig and rat alpha s1 casein mRNA species showed greater sequence conservation in the non-coding than in the coding regions, suggesting a functional and possibly regulatory role for the non-coding regions of casein mRNA. The results provide insight into the evolution of the casein genes, and raise questions as to the role of conserved nucleotide sequences within the non-coding regions of mRNA species. Images Fig. 1. PMID:6548375

Python Radiative Transfer Emission code (PyRaTE): non-LTE spectral lines simulations

NASA Astrophysics Data System (ADS)

Tritsis, A.; Yorke, H.; Tassis, K.

2018-05-01

We describe PyRaTE, a new, non-local thermodynamic equilibrium (non-LTE) line radiative transfer code developed specifically for post-processing astrochemical simulations. Population densities are estimated using the escape probability method. When computing the escape probability, the optical depth is calculated towards all directions with density, molecular abundance, temperature and velocity variations all taken into account. A very easy-to-use interface, capable of importing data from simulations outputs performed with all major astrophysical codes, is also developed. The code is written in PYTHON using an "embarrassingly parallel" strategy and can handle all geometries and projection angles. We benchmark the code by comparing our results with those from RADEX (van der Tak et al. 2007) and against analytical solutions and present case studies using hydrochemical simulations. The code will be released for public use.

TRAC-PF1 code verification with data from the OTIS test facility. [Once-Through Intergral System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Childerson, M.T.; Fujita, R.K.

1985-01-01

A computer code (TRAC-PF1/MOD1) developed for predicting transient thermal and hydraulic integral nuclear steam supply system (NSSS) response was benchmarked. Post-small break loss-of-coolant accident (LOCA) data from a scaled, experimental facility, designated the One-Through Integral System (OTIS), were obtained for the Babcock and Wilcox NSSS and compared to TRAC predictions. The OTIS tests provided a challenging small break LOCA data set for TRAC verification. The major phases of a small break LOCA observed in the OTIS tests included pressurizer draining and loop saturation, intermittent reactor coolant system circulation, boiler-condenser mode, and the initial stages of refill. The TRAC code wasmore » successful in predicting OTIS loop conditions (system pressures and temperatures) after modification of the steam generator model. In particular, the code predicted both pool and auxiliary-feedwater initiated boiler-condenser mode heat transfer.« less

Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development.

PubMed

Ikegami, Kohta; Ohgane, Jun; Tanaka, Satoshi; Yagi, Shintaro; Shiota, Kunio

2009-01-01

Genes constitute only a small proportion of the mammalian genome, the majority of which is composed of non-genic repetitive elements including interspersed repeats and satellites. A unique feature of the mammalian genome is that there are numerous tissue-dependent, differentially methylated regions (T-DMRs) in the non-repetitive sequences, which include genes and their regulatory elements. The epigenetic status of T-DMRs varies from that of repetitive elements and constitutes the DNA methylation profile genome-wide. Since the DNA methylation profile is specific to each cell and tissue type, much like a fingerprint, it can be used as a means of identification. The formation of DNA methylation profiles is the basis for cell differentiation and development in mammals. The epigenetic status of each T-DMR is regulated by the interplay between DNA methyltransferases, histone modification enzymes, histone subtypes, non-histone nuclear proteins and non-coding RNAs. In this review, we will discuss how these epigenetic factors cooperate to establish cell- and tissue-specific DNA methylation profiles.

Staphylococcus aureus Transcriptome Architecture: From Laboratory to Infection-Mimicking Conditions

PubMed Central

Depke, Maren; Pané-Farré, Jan; Debarbouille, Michel; van der Kooi-Pol, Magdalena M.; Guérin, Cyprien; Dérozier, Sandra; Hiron, Aurelia; Jarmer, Hanne; Leduc, Aurélie; Michalik, Stephan; Reilman, Ewoud; Schaffer, Marc; Schmidt, Frank; Bessières, Philippe; Noirot, Philippe; Hecker, Michael; Msadek, Tarek; Völker, Uwe; van Dijl, Jan Maarten

2016-01-01

Staphylococcus aureus is a major pathogen that colonizes about 20% of the human population. Intriguingly, this Gram-positive bacterium can survive and thrive under a wide range of different conditions, both inside and outside the human body. Here, we investigated the transcriptional adaptation of S. aureus HG001, a derivative of strain NCTC 8325, across experimental conditions ranging from optimal growth in vitro to intracellular growth in host cells. These data establish an extensive repertoire of transcription units and non-coding RNAs, a classification of 1412 promoters according to their dependence on the RNA polymerase sigma factors SigA or SigB, and allow identification of new potential targets for several known transcription factors. In particular, this study revealed a relatively low abundance of antisense RNAs in S. aureus, where they overlap only 6% of the coding genes, and only 19 antisense RNAs not co-transcribed with other genes were found. Promoter analysis and comparison with Bacillus subtilis links the small number of antisense RNAs to a less profound impact of alternative sigma factors in S. aureus. Furthermore, we revealed that Rho-dependent transcription termination suppresses pervasive antisense transcription, presumably originating from abundant spurious transcription initiation in this A+T-rich genome, which would otherwise affect expression of the overlapped genes. In summary, our study provides genome-wide information on transcriptional regulation and non-coding RNAs in S. aureus as well as new insights into the biological function of Rho and the implications of spurious transcription in bacteria. PMID:27035918

Fine-structure mapping of the firA gene, a locus involved in the phenotypic expression of rifampin resistance in Escherichia.

PubMed Central

Lathe, R

1977-01-01

The firA (Ts)200 mutation not only eliminates the resistance to rifampin of certain genetically resistant strains, but, moreover, renders ribonucleic acid synthesis thermolabile. The firA gene has been mapped by P1 tranduction and is located extremely close to the structural gene for deoxyribonucleic acid polymerase III at 4 min on the Escherichia coli linkage map. PMID:330494

Biochemical transformation of lignin for deriving valued commodities from lignocellulose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gall, Daniel L.; Ralph, John; Donohue, Timothy J.

The biochemical properties of lignin present major obstacles to deriving societally beneficial entities from lignocellulosic biomass, an abundant and renewable feedstock. Similar to other biopolymers such as polysaccharides, polypeptides, and ribonucleic acids, lignin polymers are derived from multiple types of monomeric units. However, lignin’s renowned recalcitrance is largely attributable to its racemic nature and the variety of covalent inter-unit linkages through which its aromatic monomers are linked. Indeed, unlike other biopolymers whose monomers are consistently inter-linked by a single type of covalent bond, the monomeric units in lignin are linked via non-enzymatic, combinatorial radical coupling reactions that give rise tomore » a variety of inter-unit covalent bonds in mildly branched racemic polymers. Yet, despite the chemical complexity and stability of lignin, significant strides have been made in recent years to identify routes through which valued commodities can be derived from it. This paper discusses emerging biological and biochemical means through which degradation of lignin to aromatic monomers can lead to the derivation of commercially valuable products.« less

Biochemical transformation of lignin for deriving valued commodities from lignocellulose

DOE PAGES

Gall, Daniel L.; Ralph, John; Donohue, Timothy J.; ...

2017-03-24

The biochemical properties of lignin present major obstacles to deriving societally beneficial entities from lignocellulosic biomass, an abundant and renewable feedstock. Similar to other biopolymers such as polysaccharides, polypeptides, and ribonucleic acids, lignin polymers are derived from multiple types of monomeric units. However, lignin’s renowned recalcitrance is largely attributable to its racemic nature and the variety of covalent inter-unit linkages through which its aromatic monomers are linked. Indeed, unlike other biopolymers whose monomers are consistently inter-linked by a single type of covalent bond, the monomeric units in lignin are linked via non-enzymatic, combinatorial radical coupling reactions that give rise tomore » a variety of inter-unit covalent bonds in mildly branched racemic polymers. Yet, despite the chemical complexity and stability of lignin, significant strides have been made in recent years to identify routes through which valued commodities can be derived from it. This paper discusses emerging biological and biochemical means through which degradation of lignin to aromatic monomers can lead to the derivation of commercially valuable products.« less

Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation

PubMed Central

Li, Ming; Wang, Rui; Xiang, Hua

2014-01-01

The prokaryotic immune system CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) adapts to foreign invaders by acquiring their short deoxyribonucleic acid (DNA) fragments as spacers, which guide subsequent interference to foreign nucleic acids based on sequence matching. The adaptation mechanism avoiding acquiring ‘self’ DNA fragments is poorly understood. In Haloarcula hispanica, we previously showed that CRISPR adaptation requires being primed by a pre-existing spacer partially matching the invader DNA. Here, we further demonstrate that flanking a fully-matched target sequence, a functional PAM (protospacer adjacent motif) is still required to prime adaptation. Interestingly, interference utilizes only four PAM sequences, whereas adaptation-priming tolerates as many as 23 PAM sequences. This relaxed PAM selectivity explains how adaptation-priming maximizes its tolerance of PAM mutations (that escape interference) while avoiding mis-targeting the spacer DNA within CRISPR locus. We propose that the primed adaptation, which hitches and cooperates with the interference pathway, distinguishes target from non-target by CRISPR ribonucleic acid guidance and PAM recognition. PMID:24803673

Detecting the borders between coding and non-coding DNA regions in prokaryotes based on recursive segmentation and nucleotide doublets statistics

PubMed Central

2012-01-01

Background Detecting the borders between coding and non-coding regions is an essential step in the genome annotation. And information entropy measures are useful for describing the signals in genome sequence. However, the accuracies of previous methods of finding borders based on entropy segmentation method still need to be improved. Methods In this study, we first applied a new recursive entropic segmentation method on DNA sequences to get preliminary significant cuts. A 22-symbol alphabet is used to capture the differential composition of nucleotide doublets and stop codon patterns along three phases in both DNA strands. This process requires no prior training datasets. Results Comparing with the previous segmentation methods, the experimental results on three bacteria genomes, Rickettsia prowazekii, Borrelia burgdorferi and E.coli, show that our approach improves the accuracy for finding the borders between coding and non-coding regions in DNA sequences. Conclusions This paper presents a new segmentation method in prokaryotes based on Jensen-Rényi divergence with a 22-symbol alphabet. For three bacteria genomes, comparing to A12_JR method, our method raised the accuracy of finding the borders between protein coding and non-coding regions in DNA sequences. PMID:23282225

Transmission line based thermoacoustic imaging of small animals

NASA Astrophysics Data System (ADS)

Omar, Murad; Kellnberger, Stephan; Sergiadis, George; Razansky, Daniel; Ntziachristos, Vasilis

2013-06-01

We have generated high resolution images of RF-Contrast in small animals using nearfield thermoacoustic system. This enables us to see some anatomical features of a mouse such as the heart, the spine and the boundary. OCIS codes: (000.0000) General; (000.0000) General [8-pt. type. For codes, see www.opticsinfobase.org/submit/ocis.

48 CFR 19.303 - Determining North American Industry Classification System (NAICS) codes and size standards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Determining North American Industry Classification System (NAICS) codes and size standards. 19.303 Section 19.303 Federal Acquisition... of Small Business Status for Small Business Programs 19.303 Determining North American Industry...

48 CFR 19.303 - Determining North American Industry Classification System (NAICS) codes and size standards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Industry Classification System (NAICS) codes and size standards. 19.303 Section 19.303 Federal Acquisition... of Small Business Status for Small Business Programs 19.303 Determining North American Industry... user, the added text is set forth as follows: 19.303 Determining North American Industry Classification...

78 FR 23495 - Approval and Promulgation of Air Quality Implementation Plans; Illinois; Small Container...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

...) which specify that Illinois' surface coating VOC emission limitations shall not apply to touch-up and... Administrative Code (Ill. Adm. Code) by adding a ``small container exemption'' for pleasure craft surface coating... technology (RACT) policy. DATES: This final rule is effective on May 20, 2013. ADDRESSES: EPA has established...

Potential functions of microRNAs in starch metabolism and development revealed by miRNA transcriptome profiling of cassava cultivars and their wild progenitor.

PubMed

Chen, Xin; Xia, Jing; Xia, Zhiqiang; Zhang, Hefang; Zeng, Changying; Lu, Cheng; Zhang, Weixiong; Wang, Wenquan

2015-02-04

MicroRNAs (miRNAs) are small (approximately 21 nucleotide) non-coding RNAs that are key post-transcriptional gene regulators in eukaryotic organisms. More than 100 cassava miRNAs have been identified in a conservation analysis and a repertoire of cassava miRNAs have also been characterised by next-generation sequencing (NGS) in recent studies. Here, using NGS, we profiled small non-coding RNAs and mRNA genes in two cassava cultivars and their wild progenitor to identify and characterise miRNAs that are potentially involved in plant growth and starch biosynthesis. Six small RNA and six mRNA libraries from leaves and roots of the two cultivars, KU50 and Arg7, and their wild progenitor, W14, were subjected to NGS. Analysis of the sequencing data revealed 29 conserved miRNA families and 33 new miRNA families. Together, these miRNAs potentially targeted a total of 360 putative target genes. Whereas 16 miRNA families were highly expressed in cultivar leaves, another 13 miRNA families were highly expressed in storage roots of cultivars. Co-expression analysis revealed that the expression level of some targets had negative relationship with their corresponding miRNAs in storage roots and leaves; these targets included MYB33, ARF10, GRF1, RD19, APL2, NF-YA3 and SPL2, which are known to be involved in plant development, starch biosynthesis and response to environmental stimuli. The identified miRNAs, target mRNAs and target gene ontology annotation all shed light on the possible functions of miRNAs in Manihot species. The differential expression of miRNAs between cultivars and their wild progenitor, together with our analysis of GO annotation and confirmation of miRNA: target pairs, might provide insight into know the differences between wild progenitor and cultivated cassava.

Short non-coding RNAs as bacteria species identifiers detected by surface plasmon resonance enhanced common path interferometry

NASA Astrophysics Data System (ADS)

Greef, Charles; Petropavlovskikh, Viatcheslav; Nilsen, Oyvind; Khattatov, Boris; Plam, Mikhail; Gardner, Patrick; Hall, John

2008-04-01

Small non-coding RNA sequences have recently been discovered as unique identifiers of certain bacterial species, raising the possibility that they can be used as highly specific Biowarfare Agent detection markers in automated field deployable integrated detection systems. Because they are present in high abundance they could allow genomic based bacterial species identification without the need for pre-assay amplification. Further, a direct detection method would obviate the need for chemical labeling, enabling a rapid, efficient, high sensitivity mechanism for bacterial detection. Surface Plasmon Resonance enhanced Common Path Interferometry (SPR-CPI) is a potentially market disruptive, high sensitivity dual technology that allows real-time direct multiplex measurement of biomolecule interactions, including small molecules, nucleic acids, proteins, and microbes. SPR-CPI measures differences in phase shift of reflected S and P polarized light under Total Internal Reflection (TIR) conditions at a surface, caused by changes in refractive index induced by biomolecular interactions within the evanescent field at the TIR interface. The measurement is performed on a microarray of discrete 2-dimensional areas functionalized with biomolecule capture reagents, allowing simultaneous measurement of up to 100 separate analytes. The optical beam encompasses the entire microarray, allowing a solid state detector system with no scanning requirement. Output consists of simultaneous voltage measurements proportional to the phase differences resulting from the refractive index changes from each microarray feature, and is automatically processed and displayed graphically or delivered to a decision making algorithm, enabling a fully automatic detection system capable of rapid detection and quantification of small nucleic acids at extremely sensitive levels. Proof-of-concept experiments on model systems and cell culture samples have demonstrated utility of the system, and efforts are in progress for full development and deployment of the device. The technology has broad applicability as a universal detection platform for BWA detection, medical diagnostics, and drug discovery research, and represents a new class of instrumentation as a rapid, high sensitivity, label-free methodology.

In silico identification and characterization of conserved miRNAs and their target genes in sweet potato (Ipomoea batatas L.) Expressed Sequence Tags (ESTs)

PubMed Central

Dehury, Budheswar; Panda, Debashis; Sahu, Jagajjit; Sahu, Mousumi; Sarma, Kishore; Barooah, Madhumita; Sen, Priyabrata; Modi, Mahendra Kumar

2013-01-01

The endogenous small non-coding micro RNAs (miRNAs), which are typically ~21–24 nt nucleotides, play a crucial role in regulating the intrinsic normal growth of cells and development of the plants as well as in maintaining the integrity of genomes. These small non-coding RNAs function as the universal specificity factors in post-transcriptional gene silencing. Discovering miRNAs, identifying their targets, and further inferring miRNA functions is a routine process to understand normal biological processes of miRNAs and their roles in the development of plants. Comparative genomics based approach using expressed sequence tags (EST) and genome survey sequences (GSS) offer a cost-effective platform for identification and characterization of miRNAs and their target genes in plants. Despite the fact that sweet potato (Ipomoea batatas L.) is an important staple food source for poor small farmers throughout the world, the role of miRNA in various developmental processes remains largely unknown. In this paper, we report the computational identification of miRNAs and their target genes in sweet potato from their ESTs. Using comparative genomics-based approach, 8 potential miRNA candidates belonging to miR168, miR2911, and miR156 families were identified from 23 406 ESTs in sweet potato. A total of 42 target genes were predicted and their probable functions were illustrated. Most of the newly identified miRNAs target transcription factors as well as genes involved in plant growth and development, signal transduction, metabolism, defense, and stress response. The identification of miRNAs and their targets is expected to accelerate the pace of miRNA discovery, leading to an improved understanding of the role of miRNA in development and physiology of sweet potato, as well as stress response. PMID:24067297

Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhi, Xiuyi; Giroux-Leprieur, Etienne; Respiratory Diseases and Thoracic Oncology Department, Ambroise Pare Hospital – APHP, Versailles Saint Quentin en Yvelines University, 9 Avenue Charles de Gaulle, 92100, Boulogne-Billancourt

2015-10-02

Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studiesmore » indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.« less

Correlators in simultaneous measurement of non-commuting qubit observables

NASA Astrophysics Data System (ADS)

Atalaya, Juan; Hacohen-Gourgy, Shay; Martin, Leigh S.; Siddiqi, Irfan; Korotkov, Alexander N.

We consider simultaneous continuous measurement of non-commuting qubit observables and analyze multi-time correlators 〈i κ1 (t1) ^i κN (tN) 〉 for output signals i κ (t) from the detectors. Both informational (''spooky'') and phase backactions from cQED-type measurements with phase-sensitive amplifiers are taken into account. We find an excellent agreement between analytical results and experimental data for two-time correlators of the output signals from simultaneous measurement of qubit observables σx and σφ =σx cosφ +σy sinφ . The correlators can be used to extract small deviations of experimental parameters, e.g., phase backaction and residual Rabi frequency. The multi-time correlators are important in analysis of Bacon-Shor error correction/detection codes, operated with continuous measurements.

Coding for Single-Line Transmission

NASA Technical Reports Server (NTRS)

Madison, L. G.

1983-01-01

Digital transmission code combines data and clock signals into single waveform. MADCODE needs four standard integrated circuits in generator and converter plus five small discrete components. MADCODE allows simple coding and decoding for transmission of digital signals over single line.

VizieR Online Data Catalog: FARGO_THORIN 1.0 hydrodynamic code (Chrenko+, 2017)

NASA Astrophysics Data System (ADS)

Chrenko, O.; Broz, M.; Lambrechts, M.

2017-07-01

This archive contains the source files, documentation and example simulation setups of the FARGO_THORIN 1.0 hydrodynamic code. The program was introduced, described and used for simulations in the paper. It is built on top of the FARGO code (Masset, 2000A&AS..141..165M, Baruteau & Masset, 2008ApJ...672.1054B) and it is also interfaced with the REBOUND integrator package (Rein & Liu, 2012A&A...537A.128R). THORIN stands for Two-fluid HydrOdynamics, the Rebound integrator Interface and Non-isothermal gas physics. The program is designed for self-consistent investigations of protoplanetary systems consisting of a gas disk, a disk of small solid particles (pebbles) and embedded protoplanets. Code features: I) Non-isothermal gas disk with implicit numerical solution of the energy equation. The implemented energy source terms are: Compressional heating, viscous heating, stellar irradiation, vertical escape of radiation, radiative diffusion in the midplane and radiative feedback to accretion heating of protoplanets. II) Planets evolved in 3D, with close encounters allowed. The orbits are integrated using the IAS15 integrator (Rein & Spiegel, 2015MNRAS.446.1424R). The code detects the collisions among planets and resolve them as mergers. III) Refined treatment of the planet-disk gravitational interaction. The code uses a vertical averaging of the gravitational potential, as outlined in Muller & Kley (2012A&A...539A..18M). IV) Pebble disk represented by an Eulerian, presureless and inviscid fluid. The pebble dynamics is affected by the Epstein gas drag and optionally by the diffusive effects. We also implemented the drag back-reaction term into the Navier-Stokes equation for the gas. Archive summary: ------------------------------------------------------------------------- directory/file Explanation ------------------------------------------------------------------------- /in_relax Contains setup of the first example simulation /in_wplanet Contains setup of the second example simulation /srcmain Contains the source files of FARGOTHORIN /src_reb Contains the source files of the REBOUND integrator package to be linked with THORIN GUNGPL3 GNU General Public License, version 3 LICENSE License agreement README Simple user's guide UserGuide.pdf Extended user's guide refman.pdf Programer's guide ----------------------------------------------------------------------------- (1 data file).