Circulating microRNAs as Potential Biomarkers of Infectious Disease

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Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

2017-01-01

microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

Diterpenes Synthesized from the Natural Serrulatane Leubethanol and Their in Vitro Activities against Mycobacterium tuberculosis

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Ricardo Escarcena

2015-04-01

Full Text Available Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity against the H37Rv strain of Mycobacterium tuberculosis. Some compounds showed antimycobacterial selectivity indices higher than leubethanol.

Altered microRNA Signatures in Sputum of Patients with Active Pulmonary Tuberculosis

OpenAIRE

Yi, Zhengjun; Fu, Yurong; Ji, Rui; Li, Ruifang; Guan, Zhiyu

2012-01-01

Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differenti...

Characterization and expression patterns of small RNAs in synthesized Brassica hexaploids.

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Shen, Yanyue; Zhao, Qin; Zou, Jun; Wang, Wenliang; Gao, Yi; Meng, Jinling; Wang, Jianbo

2014-06-01

Polyploidy has played an important role in promoting plant evolution through genomic merging and doubling. We used high-throughput sequencing to compare miRNA expression profiles between Brassica hexaploid and its parents. A total of 613, 784 and 742 known miRNAs were identified in Brassica rapa, Brassica carinata, and Brassica hexaploid, respectively. We detected 618 miRNAs were differentially expressed (log(2)Ratio ≥ 1, P ≤ 0.05) between Brassica hexaploid and its parents, and 425 miRNAs were non-additively expressed in Brassica hexaploid, which suggest a trend of non-additive miRNA regulation following hybridization and polyploidization. Remarkably, majority of the non-additively expressed miRNAs in the Brassica hexaploid are repressed, and there was a bias toward repression of B. rapa miRNAs, which is consistent with the progenitor-biased gene repression in the synthetic allopolyploids. In addition, we identified 653 novel mature miRNAs in Brassica hexaploid and its parents. Finally, we found that almost all the non-additive accumulation of siRNA clusters exhibited a low-parent pattern in Brassica hexaploid. Non-additive small RNA regulation is involved in a range of biological pathways, probably providing a driving force for variation and adaptation in allopolyploids.

Immunomodulating microRNAs of mycobacterial infections.

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Bettencourt, Paulo; Pires, David; Anes, Elsa

2016-03-01

MicroRNAs are a class of small non-coding RNAs that have emerged as key regulators of gene expression at the post-transcriptional level by sequence-specific binding to target mRNAs. Some microRNAs block translation, while others promote mRNA degradation, leading to a reduction in protein availability. A single miRNA can potentially regulate the expression of multiple genes and their encoded proteins. Therefore, miRNAs can influence molecular signalling pathways and regulate many biological processes in health and disease. Upon infection, host cells rapidly change their transcriptional programs, including miRNA expression, as a response against the invading microorganism. Not surprisingly, pathogens can also alter the host miRNA profile to their own benefit, which is of major importance to scientists addressing high morbidity and mortality infectious diseases such as tuberculosis. In this review, we present recent findings on the miRNAs regulation of the host response against mycobacterial infections, providing new insights into host-pathogen interactions. Understanding these findings and its implications could reveal new opportunities for designing better diagnostic tools, therapies and more effective vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Construction and analysis of the transcription factor-microRNA co-regulatory network response to Mycobacterium tuberculosis: a view from the blood.

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Lin, Yan; Duan, Zipeng; Xu, Feng; Zhang, Jiayuan; Shulgina, Marina V; Li, Fan

2017-01-01

Mycobacterium tuberculosis ( Mtb ) infection has been regional outbreak, recently. The traditional focus on the patterns of "reductionism" which was associated with single molecular changes has been unable to meet the demand of early diagnosis and clinical application when current tuberculosis infection happened. In this study, we employed a systems biology approach to collect large microarray data sets including mRNAs and microRNAs (miRNAs) to identify the differentially expressed mRNAs and miRNAs in the whole blood of TB patients. The aim was to identify key genes associated with the immune response in the pathogenic process of tuberculosis by analyzing the co-regulatory network that was consisted of transcription factors and miRNAs as well as their target genes. The network along with their co-regulatory genes was analyzed utilizing Transcriptional Regulatory Element Database (TRED) and Database for Annotation, Visualization and Integrated Discovery (DAVID). We got 21 (19 up-regulated and 2 down-regulated) differentially expressed genes that were co-regulated by transcription factors and miRNAs. KEGG pathway enrichment analysis showed that the 21 differentially expressed genes were predominantly involved in Tuberculosis signaling pathway, which may play a major role in tuberculosis biological process. Quantitative real-time PCR was performed to verify the over expression of co-regulatory genes ( FCGR1A and CEBPB ). The genetic expression was correlated with clinicopathological characteristics in TB patients and inferences drawn. Our results suggest the TF-miRNA gene co-regulatory network may help us further understand the molecular mechanism of immune response to tuberculosis and provide us a new angle of future biomarker and therapeutic targets.

microRNAs in mycobacterial disease: friend or foe?

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Manali D Mehta

2014-07-01

Full Text Available As the role of microRNA in all aspects of biology continues to be unraveled, the interplay between microRNAs and human disease is becoming clearer. It should come of no surprise that microRNAs play a major part in the outcome of infectious diseases, since early work has implicated microRNAs as regulators of the immune response. Here, we provide a review on how microRNAs influence the course of mycobacterial infections, which cause two of humanity’s most ancient infectious diseases: tuberculosis and leprosy. Evidence derived from profiling and functional experiments suggests that regulation of specific microRNAs during infection can either enhance the immune response or facilitate pathogen immune evasion. Now, it remains to be seen if the manipulation of host cell microRNA profiles can be an opportunity for therapeutic intervention for these difficult-to-treat diseases.

Identification of serum microRNA biomarkers for tuberculosis using RNA-seq.

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Zhang, Hongtai; Sun, Zhaogang; Wei, Wenjing; Liu, Zhonghui; Fleming, Joy; Zhang, Shuai; Lin, Nan; Wang, Ming; Chen, Maoshan; Xu, Yuhui; Zhou, Jie; Li, Chuanyou; Bi, Lijun; Zhou, Guangming

2014-01-01

Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold) and 6 microRNAs that are down-regulated (0.003-0.11 fold) (PmicroRNAs were up-regulated (2.05-2454.58 fold) and 11 were down-regulated (0.001-0.42 fold) (PmicroRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold), providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.

MicroRNA 17-5p regulates autophagy in Mycobacterium tuberculosis-infected macrophages by targeting Mcl-1 and STAT3.

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Kumar, Ranjeet; Sahu, Sanjaya Kumar; Kumar, Manish; Jana, Kuladip; Gupta, Pushpa; Gupta, Umesh D; Kundu, Manikuntala; Basu, Joyoti

2016-05-01

Autophagy plays a crucial role in the control of bacterial burden during Mycobacterium tuberculosis infection. MicroRNAs (miRNAs) are small non-coding RNAs that regulate immune signalling and inflammation in response to challenge by pathogens. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the role of miRNAs in regulating M. tuberculosis-induced autophagy in macrophages. Here, we demonstrate that M. tuberculosis infection leads to downregulation of miR-17 and concomitant upregulation of its targets Mcl-1 and STAT3, a transcriptional activator of Mcl-1. Forced expression of miR-17 reduces expression of Mcl-1 and STAT3 and also the interaction between Mcl-1 and Beclin-1. This is directly linked to enhanced autophagy, because Mcl-1 overexpression attenuates the effects of miR-17. At the same time, transfection with a kinase-inactive mutant of protein kinase C δ (PKCδ) (an activator of STAT3) augments M. tuberculosis-induced autophagy, and miR-17 overexpression diminishes phosphorylation of PKCδ, suggesting that an miR-17/PKC δ/STAT3 axis regulates autophagy during M. tuberculosis infection. © 2015 John Wiley & Sons Ltd.

Macrophage immunoregulatory pathways in tuberculosis.

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Rajaram, Murugesan V S; Ni, Bin; Dodd, Claire E; Schlesinger, Larry S

2014-12-01

Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs). Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of serum microRNA biomarkers for tuberculosis using RNA-seq.

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Hongtai Zhang

Full Text Available Tuberculosis (TB remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold and 6 microRNAs that are down-regulated (0.003-0.11 fold (P<0.05 in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05-2454.58 fold and 11 were down-regulated (0.001-0.42 fold (P<0.05 in latent-TB infected individuals relative to BCG- inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold, providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.

MicroRNA-155 knockout mice are susceptible to Mycobacterium tuberculosis infection.

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Iwai, Hiroki; Funatogawa, Keiji; Matsumura, Kazunori; Kato-Miyazawa, Masako; Kirikae, Fumiko; Kiga, Kotaro; Sasakawa, Chihiro; Miyoshi-Akiyama, Tohru; Kirikae, Teruo

2015-05-01

MicroRNAs (miRNAs) are short, conserved, non-coding RNA molecules that repress translation, followed by the decay of miRNA-targeted mRNAs that encode molecules involved in cell differentiation, development, immunity and apoptosis. At least six miRNAs, including microRNA-155 (miR-155), were up-regulated when born marrow-derived macrophages from C57BL/6 mice were infected with Mycobacterium tuberculosis Erdman. C57BL/6 mice intravenously infected with Erdman showed up-regulation of miR-155 in livers and lungs. Following infection, miR-155-deficient C57BL/6 mice died significantly earlier and had significantly higher numbers of CFU in lungs than wild-type mice. Moreover, fewer CD4(+) T cells, but higher numbers of monocytes and neutrophils, were present in the lungs of Erdman-infected miR-155 knockout (miR-155(-/-)) than of wild-type mice. These findings indicated that miR-155 plays a critical role in immune responses to M. tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of RNAs with Bacillus subtilis Hfq.

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Michael Dambach

Full Text Available The prevalence and characteristics of small regulatory RNAs (sRNAs have not been well characterized for Bacillus subtilis, an important model system for Gram-positive bacteria. However, B. subtilis was recently found to synthesize many candidate sRNAs during stationary phase. In the current study, we performed deep sequencing on Hfq-associated RNAs and found that a small subset of sRNAs associates with Hfq, an enigmatic RNA-binding protein that stabilizes sRNAs in Gram-negatives, but whose role is largely unknown in Gram-positive bacteria. We also found that Hfq associated with antisense RNAs, antitoxin transcripts, and many mRNA leaders. Several new candidate sRNAs and mRNA leader regions were also discovered by this analysis. Additionally, mRNA fragments overlapping with start or stop codons associated with Hfq, while, in contrast, relatively few full-length mRNAs were recovered. Deletion of hfq reduced the intracellular abundance of several representative sRNAs, suggesting that B. subtilis Hfq-sRNA interactions may be functionally significant in vivo. In general, we anticipate this catalog of Hfq-associated RNAs to serve as a resource in the functional characterization of Hfq in B. subtilis.

Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis.

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Liu, Yanhua; Wang, Xinjing; Jiang, Jing; Cao, Zhihong; Yang, Bingfen; Cheng, Xiaoxing

2011-05-01

microRNAs have a critical role in regulating innate and adaptive immunity. To understand whether microRNAs play roles in regulating immune responses to Mycobacterium tuberculosis infection in humans, microRNA expression profiling was performed in PBMCs from pulmonary tuberculosis patients and healthy controls. Analysis of expression profiles showed that expression of 30 microRNAs was significantly altered during active TB as compared with healthy controls, 28 microRNAs were up-regulated and 2 microRNAs down-regulated. miR-144* was one of the microRNAs that were overexpressed in active TB patients. Real-time RT-PCR analysis showed that miR-144* was mainly expressed in T cells. Transfection of T cells with miR-144* precursor demonstrated that miR-144* could inhibit TNF-α and IFN-γ production and T cell proliferation. It is concluded that miR-144* might involve in regulation of anti-TB immunity through modification of cytokine production and cell proliferation of T cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

MicroRNA signatures from multidrug-resistant Mycobacterium tuberculosis

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REN, NA; GAO, GUIJU; SUN, YUE; ZHANG, LING; WANG, HUIZHU; HUA, WENHAO; WAN, KANGLIN; LI, XINGWANG

2015-01-01

Tuberculosis (TB) infections, caused by multi-drug-resistant Mycobacterium tuberculosis (MDR MTB), remain a significant public health concern worldwide. The regulatory mechanisms underlying the emergence of MDR MTB strains remain to be fully elucidated, and further investigation is required in order to develop better strategies for TB control. The present study investigated the expression profile of microRNA (miRNA) in MTB strains, and examined the differences between sensitive MTB and MDR MTB using next generation sequencing (NGS) with Illumina Deep Sequencing technology to better understand the mechanisms of resistance in MDR MTB, A total of 5, 785 and 195, and 6, 290 and 595 qualified Illumina reads were obtained from two MDR MTB strains, and 6, 673 and 665, and 7, 210 and 217 qualified Illumina reads were obtained from two sensitive MTB strains. The overall de novo assembly of miRNA sequence data generated 62 and 62, and 95 and 112 miRNAs between the 18 and 30 bp long from sensitive MTB strains and MDR MTB strains, respectively. Comparative miRNA analysis revealed that 142 miRNAs were differentially expressed in the MDR MTB strain, compared with the sensitive MTB strain, of which 48 were upregulated and 94 were downregulated. There were six similarly expressed miRNAs between the MDR and sensitive MTB strains, and 108 miRNAs were expressed only in the MDR MTB strain. The present study acquired miRNA data from sensitive MTB and MDR MTB strains using NGS techniques, and this identification miRNAs may serve as an invaluable resource for revealing the molecular basis of the regulation of expression associated with the mechanism of drug-resistance in MTB. PMID:26324150

MicroRNA signatures from multidrug‑resistant Mycobacterium tuberculosis.

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Ren, Na; Gao, Guiju; Sun, Yue; Zhang, Ling; Wang, Huizhu; Hua, Wenhao; Wan, Kanglin; Li, Xingwang

2015-11-01

Tuberculosis (TB) infections, caused by multidrug‑resistant Mycobacterium tuberculosis (MDR MTB), remain a significant public health concern worldwide. The regulatory mechanisms underlying the emergence of MDR MTB strains remain to be fully elucidated, and further investigation is required in order to develop better strategies for TB control. The present study investigated the expression profile of microRNA (miRNA) in MTB strains, and examined the differences between sensitive MTB and MDR MTB using next generation sequencing (NGS) with Illumina Deep Sequencing technology to better understand the mechanisms of resistance in MDR MTB, A total of 5, 785 and 195, and 6, 290 and 595 qualified Illumina reads were obtained from two MDR MTB strains, and 6, 673 and 665, and 7, 210 and 217 qualified Illumina reads were obtained from two sensitive MTB strains. The overall de novo assembly of miRNA sequence data generated 62 and 62, and 95 and 112 miRNAs between the 18 and 30 bp long from sensitive MTB strains and MDR MTB strains, respectively. Comparative miRNA analysis revealed that 142 miRNAs were differentially expressed in the MDR MTB strain, compared with the sensitive MTB strain, of which 48 were upregulated and 94 were downregulated. There were six similarly expressed miRNAs between the MDR and sensitive MTB strains, and 108 miRNAs were expressed only in the MDR MTB strain. The present study acquired miRNA data from sensitive MTB and MDR MTB strains using NGS techniques, and this identification miRNAs may serve as an invaluable resource for revealing the molecular basis of the regulation of expression associated with the mechanism of drug‑resistance in MTB.

MicroRNA expression signatures in lungs of mice infected with Mycobacterium tuberculosis.

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Malardo, Thiago; Gardinassi, Luiz Gustavo; Moreira, Bernardo Pereira; Padilha, Éverton; Lorenzi, Júlio César Cetrulo; Soares, Luana Silva; Gembre, Ana Flávia; Fontoura, Isabela Cardoso; de Almeida, Luciana Previato; de Miranda Santos, Isabel Kinney Ferreira; Silva, Célio Lopes; Coelho-Castelo, Arlete Aparecida Martins

2016-12-01

Tuberculosis (TB) is a major public health concern worldwide; however the factors that account for resistance or susceptibility to disease are not completely understood. Although some studies suggest that the differential expression of miRNAs in peripheral blood of TB patients could be useful as biomarkers of active disease, their involvement during the inflammatory process in lungs of infected individuals is unknown. Here, we evaluated the global expression of miRNAs in the lungs of mice experimentally infected with Mycobacterium tuberculosis on 30 and 60 days post-infection. We observed that several miRNAs were differentially expressed compared to uninfected mice. Furthermore, we verified that the expression of miR-135b, miR-21, miR-155, miR-146a, and miR-146b was significantly altered in distinct leukocyte subsets isolated from lungs of infected mice, while genes potentially targeted by those miRNAs were associated with a diversity of immune related molecular pathways. Importantly, we validated the inhibition of Pellino 1 expression by miR-135b in vitro. Overall, this study contributes to the understanding of the dynamics of miRNA expression in lungs during experimental TB and adds further perspectives into the role of miRNAs on the regulation of immune processes such as leukocyte activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mycobacterium tuberculosis decreases human macrophage IFN-γ responsiveness through miR-132 and miR-26a.

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Ni, Bin; Rajaram, Murugesan V S; Lafuse, William P; Landes, Michelle B; Schlesinger, Larry S

2014-11-01

IFN-γ-activated macrophages play an essential role in controlling intracellular pathogens; however, macrophages also serve as the cellular home for the intracellular pathogen Mycobacterium tuberculosis. Based on previous evidence that M. tuberculosis can modulate host microRNA (miRNA) expression, we examined the miRNA expression profile of M. tuberculosis-infected primary human macrophages. We identified 31 differentially expressed miRNAs in primary human macrophages during M. tuberculosis infection by NanoString and confirmed our findings by quantitative real-time RT-PCR. In addition, we determined a role for two miRNAs upregulated upon M. tuberculosis infection, miR-132 and miR-26a, as negative regulators of transcriptional coactivator p300, a component of the IFN-γ signaling cascade. Knockdown expression of miR-132 and miR-26a increased p300 protein levels and improved transcriptional, translational, and functional responses to IFN-γ in human macrophages. Collectively, these data validate p300 as a target of miR-132 and miR-26a, and demonstrate a mechanism by which M. tuberculosis can limit macrophage responses to IFN-γ by altering host miRNA expression. Copyright © 2014 by The American Association of Immunologists, Inc.

A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts

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Fergal J. Duffy

2018-04-01

Full Text Available Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs regulate the host response to MTB and circulating miRNAs (c-miRNAs have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.

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Duffy, Fergal J; Thompson, Ethan; Downing, Katrina; Suliman, Sara; Mayanja-Kizza, Harriet; Boom, W Henry; Thiel, Bonnie; Weiner Iii, January; Kaufmann, Stefan H E; Dover, Drew; Tabb, David L; Dockrell, Hazel M; Ottenhoff, Tom H M; Tromp, Gerard; Scriba, Thomas J; Zak, Daniel E; Walzl, Gerhard

2018-01-01

Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

Protein synthesis directed by cowpea mosaic virus RNAs

International Nuclear Information System (INIS)

Stuik, E.

1979-01-01

The thesis concerns the proteins synthesized under direction of Cowpea mosaic virus RNAs. Sufficient radioactive labelling of proteins was achieved when 35 S as sulphate was administered to intact Vigna plants, cultivated in Hoagland solution. The large polypeptides synthesized under direction of B- and M-RNA are probably precursor molecules from which the coat proteins are generated by a mechanism of posttranslational cleavage. (Auth.)

Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB PR10 strain

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Mohd Zakihalani A. Halim

2016-03-01

Full Text Available Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10 isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. Keywords: Mycobacterium tuberculosis, Genome, MDR, Extrapulmonary

Common features of tuberculosis and sarcoidosis

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Esmaeil Mortaz

2016-01-01

. However, it is often difficult to differentiate sarcoidosis from TB, especially when caseous necrosis is not seen and acid-fast staining is negative in the biopsy specimen of patient with TB. Granulomatous inflammation in sarcoidosis is believed to be caused by the presence of a persistent poorly degradable unknown antigen in combination with a nonresolving host response. M. tuberculosis has been extensively studied as a possible cause of sarcoidosis. Results suggest that granulomas form in the lungs as a result of the immune response to inhaled M. tuberculosis and serve as the central site of host–pathogen interaction during M. tuberculosis infection. M. tuberculosis DNA detection in sarcoidosis samples by traditional polymerase chain reaction (PCR has been used for the pathological study of sarcoidosis; however, it is likely that real time quantitative PCR analysis of specific mRNAs and microRNAs will be necessary as a sensitive, precise, and rapid diagnostic test for detecting trace of TB in Sarcoidosis. In conclusion, diagnosis of sarcoidosis in areas with a high burden of TB poses a significant challenge. Improved diagnostic tests including genetic tests can improve our knowledge and help in distinguishing these two diseases.

The Clinical Application of MicroRNAs in Infectious Disease

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Ruth E. Drury

2017-09-01

Full Text Available MicroRNAs (miRNAs are short single-stranded non-coding RNA sequences that posttranscriptionally regulate up to 60% of protein encoding genes. Evidence is emerging that miRNAs are key mediators of the host response to infection, predominantly by regulating proteins involved in innate and adaptive immune pathways. miRNAs can govern the cellular tropism of some viruses, are implicated in the resistance of some individuals to infections like HIV, and are associated with impaired vaccine response in older people. Not surprisingly, pathogens have evolved ways to undermine the effects of miRNAs on immunity. Recognition of this has led to new experimental treatments, RG-101 and Miravirsen—hepatitis C treatments which target host miRNA. miRNAs are being investigated as novel infection biomarkers, and they are being used to design attenuated vaccines, e.g., against Dengue virus. This comprehensive review synthesizes current knowledge of miRNA in host response to infection with emphasis on potential clinical applications, along with an evaluation of the challenges still to be overcome.

The Clinical Application of MicroRNAs in Infectious Disease.

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Drury, Ruth E; O'Connor, Daniel; Pollard, Andrew J

2017-01-01

MicroRNAs (miRNAs) are short single-stranded non-coding RNA sequences that posttranscriptionally regulate up to 60% of protein encoding genes. Evidence is emerging that miRNAs are key mediators of the host response to infection, predominantly by regulating proteins involved in innate and adaptive immune pathways. miRNAs can govern the cellular tropism of some viruses, are implicated in the resistance of some individuals to infections like HIV, and are associated with impaired vaccine response in older people. Not surprisingly, pathogens have evolved ways to undermine the effects of miRNAs on immunity. Recognition of this has led to new experimental treatments, RG-101 and Miravirsen-hepatitis C treatments which target host miRNA. miRNAs are being investigated as novel infection biomarkers, and they are being used to design attenuated vaccines, e.g., against Dengue virus. This comprehensive review synthesizes current knowledge of miRNA in host response to infection with emphasis on potential clinical applications, along with an evaluation of the challenges still to be overcome.

Mycobacterium tuberculosis controls microRNA-99b (miR-99b) expression in infected murine dendritic cells to modulate host immunity.

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Singh, Yogesh; Kaul, Vandana; Mehra, Alka; Chatterjee, Samit; Tousif, Sultan; Dwivedi, Ved Prakash; Suar, Mrutyunjay; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

2013-02-15

Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies.

Mycobacterium tuberculosis Controls MicroRNA-99b (miR-99b) Expression in Infected Murine Dendritic Cells to Modulate Host Immunity*

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Singh, Yogesh; Kaul, Vandana; Mehra, Alka; Chatterjee, Samit; Tousif, Sultan; Dwivedi, Ved Prakash; Suar, Mrutyunjay; Van Kaer, Luc; Bishai, William R.; Das, Gobardhan

2013-01-01

Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies. PMID:23233675

Competitive Endogenous RNAs in Prostate Cancer

Science.gov (United States)

2015-01-01

that there is a negative correlation between GAS5 and miR-21, and microRNAs silence target genes via RISC complex carrying AGO2, next we asked whether...GAS5 directly interacts with miR-12 in the RISC complex. Thus, we synthesized GAS5 RNA probe and labeled with biotin and then mixed with cellular

Messenger RNas : their utilization and degradation during pollen germination and tube growth

Directory of Open Access Journals (Sweden)

Joseph P. Mascarenhas

2014-01-01

Full Text Available During pollen germination and tube growth at least 230 new proteins are synthesized, as determined by 35S-methionime labeling and two dimensional gel electrophoretic analysis of the labeled proteins. The same number and pattern of protein spots is seen whether or not actinomycin D is included in the, medium, indicating that the mRNAs present in the unger-minated pollen grain and those newly synthesized code for the same proteins. The genetic program during at least the latter part of pollen maturation prior to anthesis and that during pollen germination and tube growth thus appears to be similar if not identical. During the first hour of pollen tube growth about 500/0 of the protein synthesis that occurs utilizes previously synthesized mRNAs. The remaining 50% occurs on newly made mRNAs. The ungerminated mature pollen grain contains 196 pg of RNA and approximately 6 X 106 molecules of poly(A+ RNA, i.e. mRNAs. The rate of protein synthesis corrected for internal pool changes in the labeled amino acid used (3H-leucine is highest during the first 15 min of pollen tube growth. The rate decreases rapidly thereafter for the next 45 min. Concurrent with the reduction in rate of protein synthesis there is a reduction in the poly(A content of the pollen RNA and in the amount of poly(A per pollen, grain. The total RNA per pollen grain, however, appears not to change during this period.

MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study.

Science.gov (United States)

Zheng, Meng-Li; Zhou, Nai-Kang; Luo, Cheng-Hua

2016-11-01

In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma.

Science.gov (United States)

Yuan, Yang; Jiaoming, Li; Xiang, Wang; Yanhui, Liu; Shu, Jiang; Maling, Gou; Qing, Mao

2018-05-01

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma.

Altered microRNA expression levels in mononuclear cells of patients with pulmonary and pleural tuberculosis and their relation with components of the immune response.

Science.gov (United States)

Spinelli, Silvana V; Diaz, Ariana; D'Attilio, Luciano; Marchesini, Marcela M; Bogue, Cristina; Bay, Maria L; Bottasso, Oscar A

2013-03-01

Different lines of evidence demonstrate that microRNAs (miRNAs) play an important role in host-pathogen interactions. In this study we investigated the expression patterns of several miRNAs, most of them involved in regulating inflammatory responses, in patients with tuberculosis (TB). In order to understand the events occurring at the site of infection, we employed mononuclear cells obtained from both peripheral blood (PBMC) and pleural fluids (PFMC) of patients. Interestingly, we found that the miRNA signature of each compartment is different, with a strong down-regulation in PFMCs of miR-223, miR-144* and miR-421. In addition, we observed that miR-146a expression is also down-regulated in tuberculosis patients, both in PBMCs and PFMCs while miR-424 levels are elevated only in the peripheral compartments. We also showed that systemic expression of these miRNAs changes upon specific treatment and is associated with IL-6 levels, a cytokine playing a substantial role in TB immunopathology. Present results contribute to a better knowledge of the host responses in TB pathogenesis, pointing out the role of miRNAs in this disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.

Science.gov (United States)

Furuse, Yuki; Finethy, Ryan; Saka, Hector A; Xet-Mull, Ana M; Sisk, Dana M; Smith, Kristen L Jurcic; Lee, Sunhee; Coers, Jörn; Valdivia, Raphael H; Tobin, David M; Cullen, Bryan R

2014-01-01

MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ∼ 23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin.

Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.

Directory of Open Access Journals (Sweden)

Yuki Furuse

Full Text Available MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ∼ 23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin.

2-Thiophenecarboxylic acid hydrazide Derivatives: Synthesis and Anti-Tuberculosis Studies

Science.gov (United States)

Fahmi, M. R. G.; Khumaidah, L.; Ilmiah, T. K.; Fadlan, A.; Santoso, M.

2018-04-01

One of the most frequent and widespread infectious diseases especially in developing countries is tuberculosis (TB). The number of TB drug resistant tend to increase, and there has been no new TB drug introduce since the 1960s. Six 2-Thiophenecarboxylic acid hydrazide derivatives were synthesized in 90-97% yields, and 2-thiophenecarbonylhydrazone-5, 7-dibromoisatin showed the highest activity in inhibiting M. tuberculosis H37Rv.

Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

Science.gov (United States)

Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

2012-01-01

To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Circular RNAs

DEFF Research Database (Denmark)

Han, Yi-Neng; Xia, Shengqiang; Zhang, Yuan-Yuan

2017-01-01

Circular RNAs (circRNAs) are a novel type of universal and diverse endogenous noncoding RNAs (ncRNAs) and they form a covalently closed continuous loop without 5' or 3' tails unlike linear RNAs. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhi...... and expression regulators, RBP sponges in cancer as well as current research methods of circRNAs, providing evidence for the significance of circRNAs in cancer diagnosis and clinical treatment....

Perturbed microRNA Expression by Mycobacterium tuberculosis Promotes Macrophage Polarization Leading to Pro-survival Foam Cell.

Science.gov (United States)

Ahluwalia, Pankaj Kumar; Pandey, Rajan Kumar; Sehajpal, Prabodh Kumar; Prajapati, Vijay Kumar

2017-01-01

Tuberculosis (TB) is one of the prevalent causes of death worldwide, with 95% of these deaths occurring in developing countries, like India. The causative agent, Mycobacterium tuberculosis (MTb) has the tenacious ability to circumvent the host's immune system for its own advantage. Macrophages are one of the phagocytic cells that are central to immunity against MTb. These are highly plastic cells dependent on the milieu and can showcase M1/M2 polarization. M1 macrophages are bactericidal in action, but M2 macrophages are anti-inflammatory in their immune response. This computational study is an effort to elucidate the role of miRNAs that influences the survival of MTb in the macrophage. To identify the miRNAs against critical transcription factors, we selected only conserved hits from TargetScan database. Further, validation of these miRNAs was achieved using four databases viz . DIANA-microT, miRDB, miRanda-mirSVR, and miRNAMap. All miRNAs were identified through a conserved seed sequence against the 3'-UTR of transcription factors. This bioinformatics study found that miR-27a and miR-27b has a putative binding site at 3'-UTR of IRF4, and miR-302c against IRF5. miR-155, miR-132, and miR-455-5p are predicted microRNAs against suppressor of cytokine signaling transcription factors. Several other microRNAs, which have an affinity for critical transcription factors, are also predicted in this study. This MTb-associated modulation of microRNAs to modify the expression of the target gene(s) plays a critical role in TB pathogenesis. Other than M1/M2 plasticity, MTb has the ability to convert macrophage into foam cells that are rich in lipids and cholesterol. We have highlighted few microRNAs which overlap between M2/foam cell continuums. miR-155, miR-33, miR-27a, and miR-27b plays a dual role in deciding macrophage polarity and its conversion to foam cells. This study shows a glimpse of microRNAs which can be modulated by MTb not only to prevent its elimination but also

Selective Destruction of Interleukin 23–Induced Expansion of a Major Antigen–Specific γδ T-Cell Subset in Patients With Tuberculosis

Science.gov (United States)

Gu, Jin; Xiao, Heping; Liang, Shanshan; Yang, Enzhuo; Yang, Rui; Huang, Dan; Chen, Crystal; Wang, Feifei; Shen, Ling; Chen, Zheng W.

2017-01-01

Abstract A loss of antigen-specific T-cell responses due to defective cytokine signaling during infections has not been reported. We hypothesize that tuberculosis can destroy signaling effects of selective cytokine(s) and induce exhaustion of antigen-specific T cells. To test this hypothesis, mechanistic studies were performed to examine whether and how tuberculosis blocked interleukin 23 (IL-23) and interleukin 2 (IL-2) signaling effects on a major human γδ T-cell subpopulation, phosphoantigen HMBPP–specific Vγ2Vδ2 T cells. IL-23 and IL-2 significantly expanded HMBPP-stimulated Vγ2Vδ2 T cells from subjects with latent tuberculosis infection, and IL-2 synergized the effect of IL-23. IL-23–induced expansion of Vγ2Vδ2 T cells involved STAT3. Surprisingly, patients with tuberculosis exhibited a selective destruction of IL-23–induced expansion of these cells. The tuberculosis-driven destruction of IL-23 signaling coincided with decreases of expression and phosphorylation of STAT3. Interestingly, impairing of STAT3 was linked to marked increases in the microRNAs (miRNAs) hsa-miR-337-3p and hsa-miR-125b-5p in Vγ2Vδ2 T cells from patients with tuberculosis. Downregulation of hsa-miR-337-3p and hsa-miR-125b-5p by miRNA sponges improved IL-23–mediated expansion of Vγ2Vδ2 T cells and restored the ability of these cells to produce anti–tuberculosis cytokines. These results support our hypothesis that tuberculosis can selectively impair a cytokine effect while sparing another and can induce exhaustion of T cells in response to the respective cytokine. PMID:27789724

Targeted gene deletion of miRNAs in mice by TALEN system.

Science.gov (United States)

Takada, Shuji; Sato, Tempei; Ito, Yoshiaki; Yamashita, Satoshi; Kato, Tomoko; Kawasumi, Miyuri; Kanai-Azuma, Masami; Igarashi, Arisa; Kato, Tomomi; Tamano, Moe; Asahara, Hiroshi

2013-01-01

Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs) and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A) tail worked better than that of with poly(A) tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.

Tuberculosis

International Nuclear Information System (INIS)

Aleksandrova, A.V.

1983-01-01

Classification of clinical forms of tuberculosis of respiratory organs is m ade. It is shown, that diagnosis, determination of the clinical form of pulmona ry tuberculosis, extent and phase of the process are mainly based on the data of roentgenologic studies and in certain cases tomography is preferable. Roentgenologic picture of primary tuberculosis, tuberculosis of intrathoracis l ymp nodes, dissemenated tuberculosis, focal and infiltrative tuberculosis of lungs, tuberculomas of lungs, cavernous and fibrocavernous form of pulmonary tub erculosis, cirrhotic tuberculosis of lungs, tuberculosis of upper respiratory tracks, tuberculous pleurite and tuberculosis of respiratory organs, combined wi th dust occupational diseases, has been described

Design, syntheses, and anti-tuberculosis activities of conjugates of piperazino-1,3-benzothiazin-4-ones (pBTZs) with 2,7-dimethylimidazo [1,2-a]pyridine-3-carboxylic acids and 7-phenylacetyl cephalosporins.

Science.gov (United States)

Majewski, Mark W; Tiwari, Rohit; Miller, Patricia A; Cho, Sanghyun; Franzblau, Scott G; Miller, Marvin J

2016-04-15

Tuberculosis (TB) remains one of the most threatening diseases in the world and the need for development of new therapies is dire. Herein we describe the rationale for the design and subsequent syntheses and studies of conjugates between pBTZ and both the imidazopyridine and cephalosporin scaffolds. Overall some compounds exhibited notable anti-TB activity in the range of 2-0.2 μM in the Microplate Alamar Blue (MABA) Assay. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of potential urine proteins and microRNA biomarkers for the diagnosis of pulmonary tuberculosis patients.

Science.gov (United States)

Wang, Jieru; Zhu, Xiaojie; Xiong, Xuekai; Ge, Pan; Liu, Han; Ren, Ningning; Khan, Farhan Anwar; Zhou, Xia; Zhang, Li; Yuan, Xu; Chen, Xi; Chen, Yingyu; Hu, Changmin; Robertson, Ian D; Chen, Huanchun; Guo, Aizhen

2018-04-11

This study identified urinary biomarkers for tuberculosis (TB) diagnosis. The urine proteomic profiles of 45 pulmonary tuberculosis patients prior to anti-TB treatment and 45 healthy controls were analyzed and compared using two-dimensional electrophoresis with matrix-assisted laser desorption/ionization time of flight mass spectrometry. Nineteen differentially expressed proteins were identified preliminarily, and western blotting and qRT-PCR were performed to confirm these changes at the translational and transcriptional levels, respectively, using samples from 122 additional pulmonary tuberculosis patients and 73 additional healthy controls. Two proteins, mannose-binding lectin 2 and a 35-kDa fragment of inter-α-trypsin inhibitor H4, exhibited the highest differential expression. We constructed a protein-microRNA interaction network that primarily involved complement and inflammatory responses. Eleven microRNAs from microRNA-target protein interactions were screened and validated using qRT-PCR with some of the above samples, including 97 pulmonary tuberculosis patients and 48 healthy controls. Only miR-625-3p exhibited significant differential expression (p tuberculosis diagnosis than individual biomarkers or any two-biomarker combination and generated a diagnostic sensitivity of 85.87% and a specificity of 87.50%. These novel urine biomarkers may significantly improve tuberculosis diagnosis.

Targeted gene deletion of miRNAs in mice by TALEN system.

Directory of Open Access Journals (Sweden)

Shuji Takada

Full Text Available Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A tail worked better than that of with poly(A tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation.

Directory of Open Access Journals (Sweden)

Jiang Shu

Full Text Available MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation

Science.gov (United States)

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details. PMID:26528912

Decreased Expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T Cells and Peripheral Blood from Tuberculosis Patients

Science.gov (United States)

Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M.; Jacobsen, Marc

2013-01-01

The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4+ T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease. PMID:23613882

Evaluating the potential of housekeeping genes, rRNAs, snRNAs, microRNAs and circRNAs as reference genes for the estimation of PMI.

Science.gov (United States)

Tu, Chunyan; Du, Tieshuai; Shao, Chengchen; Liu, Zengjia; Li, Liliang; Shen, Yiwen

2018-04-24

The precise estimation of postmortem interval (PMI) is a critical step in death investigation of forensic cases. Detecting the degradation of RNA in tissues by real time quantitative polymerase chain reaction (RT-qPCR) technology provides a new theoretical basis for estimation of PMI. However, most commonly used reference genes degrade over time, while previous studies seldom consider this when selecting suitable reference genes for the estimation of PMI. Studies have shown microRNAs (miRNAs) are very stable and circular RNAs (circRNAs) have recently emerged as a novel class of RNAs with high stability. We aimed to evaluate the stability of the two kinds of RNAs and normal reference genes using geNorm and NormFinder algorithms to identify tissue-specific reference genes for PMI estimation. The content of candidate RNAs from mouse heart, liver and skeletal muscle tissues were dynamically examined in 8 consecutive days after death. Among the 11 candidate genes (β-actin, Gapdh, Rps18, 5S, 18S, U6, miR-133a, miR-122, circ-AFF1, LC-Ogdh and LC-LRP6), the following genes showed prioritized stability: miR-122, miR-133a and 18S in heart tissues; LC-Ogdh, circ-AFF1 and miR-122 in liver tissues; and miR-133a, circ-AFF1 and LC-LRP6 in skeletal muscle tissues. Our results suggested that miRNAs and circRNAs were more stable as reference genes than other kinds of RNAs regarding PMI estimation. The appropriate internal control genes were not completely the same across tissue types.

Towards a new combination therapy for tuberculosis with next generation benzothiazinones

NARCIS (Netherlands)

Makarov, V.; Lechartier, B.; Zhang, M.; Neres, J.; van der Sar, A.M.; Raadsen, S.A.; Hartkoorn, R.C.; Ryabova, O.B.; Vocat, A.; Decosterd, L.A.; Widmer, N.; Buclin, T.; Bitter, W.; Andries, K.; Pojer, F.; Dyson, P.J.; Cole, S.T.

2014-01-01

The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) and show that, like BTZ043, the preclinical

Association between tuberculosis and circulating microRNA hsa-let-7b and hsa-miR-30b: A pilot study in a Chinese population.

Science.gov (United States)

Xin, Henan; Yang, Yu; Liu, Jianmin; Li, Xiangwei; Li, Mufei; Feng, Boxuan; Li, Zhen; Zhang, Haoran; Li, Hengjing; Shen, Fei; Guan, Ling; Gao, Lei

2016-07-01

Tuberculosis remains one of the world's deadliest communicable diseases. Limitations in the current diagnosis tools have heavily slowed down the step to eliminate TB. The objective of this study was to identify potential circulating miRNA associated with tuberculosis (TB) infection and disease development. Agilent human miRNA microarray was used to estimate the circulating levels of 1887 miRNAs among 34 study participants (10 patients with pulmonary TB, 13 controls with latent TB infection and 11 non-infected healthy controls). The identified miRNAs were subsequently verified by real-time qPCR. Target gene prediction and miRNA-gene network construction were further explored. A total of 119 miRNAs were identified to be in different levels between any two groups of the study population by microarray (Fold Change>2, p < 0.01). 11 most promising miRNAs were then selected for verification by real-time qPCR. The levels of hsa-let-7b-5p and hsa-miR-30b-5p were confirmed to be significantly up-regulated in pulmonary TB patients as compared to both control groups (p < 0.01). Caspase 3 was predicted to be one common target gene for these two miRNAs. None of the selected miRNA was confirmed to be related with the infection status. This pilot study suggested circulating hsa-let-7b and hsa-miR-30b might be associated with TB development by regulating the target genes involved in TLR-NF-kB mediated signal pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs

DEFF Research Database (Denmark)

Khan, Aly A; Betel, Doron; Miller, Martin L

2009-01-01

Transfection of small RNAs (such as small interfering RNAs (siRNAs) and microRNAs (miRNAs)) into cells typically lowers expression of many genes. Unexpectedly, increased expression of genes also occurs. We investigated whether this upregulation results from a saturation effect--that is, competiti...

Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4⁺ T cells and peripheral blood from tuberculosis patients.

Science.gov (United States)

Kleinsteuber, Katja; Heesch, Kerrin; Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M; Jacobsen, Marc

2013-01-01

The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4(+) T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4(+) T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease.

Health impact of external funding for HIV, tuberculosis and malaria: systematic review

NARCIS (Netherlands)

Jongh, T.E. de; Harnmeijer, J.H.; Atun, R.; Korenromp, E.L.; Zhao, J.; Puvimanasinghe, J.; Baltussen, R.M.P.M.

2014-01-01

BACKGROUND: Since 2002, development assistance for health has substantially increased, especially investments for HIV, tuberculosis (TB) and malaria control. We undertook a systematic review to assess and synthesize the existing evidence in the scientific literature on the health impacts of these

Health impact of external funding for HIV, tuberculosis and malaria: Systematic review

NARCIS (Netherlands)

T.E. De Jongh (Thyra E.); J.H. Harnmeijer (Joanne H.); R. Atun (Rifat); E.L. Korenromp (Eline); J. Zhao (Jinkou); J.P.A. Puvimanasinghe (John); R.M.P.M. Baltussen (Rob)

2014-01-01

textabstractBackground Since 2002, development assistance for health has substantially increased, especially investments for HIV, tuberculosis (TB) and malaria control. We undertook a systematic review to assess and synthesize the existing evidence in the scientific literature on the health impacts

MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2.

Science.gov (United States)

Kim, Jin Kyung; Lee, Hye-Mi; Park, Ki-Sun; Shin, Dong-Min; Kim, Tae Sung; Kim, Yi Sak; Suh, Hyun-Woo; Kim, Soo Yeon; Kim, In Soo; Kim, Jin-Man; Son, Ji-Woong; Sohn, Kyung Mok; Jung, Sung Soo; Chung, Chaeuk; Han, Sang-Bae; Yang, Chul-Su; Jo, Eun-Kyeong

2017-02-01

Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages. Mtb infection downregulated, whereas the autophagy activators upregulated, DRAM2 expression in human monocytes and macrophages by activating AMP-activated protein kinase. In addition, overexpression of MIR144* decreased DRAM2 expression and formation of autophagosomes in human monocytes, whereas inhibition of MIR144* had the opposite effect. Moreover, the levels of MIR144* were elevated, whereas DRAM2 levels were reduced, in human peripheral blood cells and tissues in TB patients, indicating the clinical significance of MIR144* and DRAM2 in human TB. Notably, DRAM2 interacted with BECN1 and UVRAG, essential components of the autophagic machinery, leading to displacement of RUBCN from the BECN1 complex and enhancement of Ptdlns3K activity. Furthermore, MIR144* and DRAM2 were critically involved in phagosomal maturation and enhanced antimicrobial effects against Mtb. Our findings identify a previously unrecognized role of human MIR144* in the inhibition of antibacterial autophagy and the innate host immune response to Mtb. Additionally, these data reveal that DRAM2 is a key coordinator of autophagy activation that enhances antimicrobial activity against Mtb.

Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of Mycobacterium tuberculosis MazF Toxins

Science.gov (United States)

Nigam, Akanksha; Kumar, Sathish

2018-01-01

ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. PMID:29717013

Noncanonical microRNAs and endogenous siRNAs in lytic infection of murine gammaherpesvirus.

Directory of Open Access Journals (Sweden)

Jing Xia

Full Text Available MicroRNA (miRNA and endogenous small interfering RNA (endo-siRNA are two essential classes of small noncoding RNAs (sncRNAs in eukaryotes. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68 (MHV68. In addition to three novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from transfer RNAs, small nucleolar RNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from that of canonical miRNAs in lengths of hairpins, base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. Besides several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to produce endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs. Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data and virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative targets of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation, and localized to membranes, suggesting their potential role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new light on their potential functions of lytic infection of MHV68.

MicroRNAs and Presbycusis.

Science.gov (United States)

Hu, Weiming; Wu, Junwu; Jiang, Wenjing; Tang, Jianguo

2018-02-01

Presbycusis (age-related hearing loss) is the most universal sensory degenerative disease in elderly people caused by the degeneration of cochlear cells. Non-coding microRNAs (miRNAs) play a fundamental role in gene regulation in almost every multicellular organism, and control the aging processes. It has been identified that various miRNAs are up- or down-regulated during mammalian aging processes in tissue-specific manners. Most miRNAs bind to specific sites on their target messenger-RNAs (mRNAs) and decrease their expression. Germline mutation may lead to dysregulation of potential miRNAs expression, causing progressive hair cell degeneration and age-related hearing loss. Therapeutic innovations could emerge from a better understanding of diverse function of miRNAs in presbycusis. This review summarizes the relationship between miRNAs and presbycusis, and presents novel miRNAs-targeted strategies against presbycusis.

MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs.

Science.gov (United States)

Shahid, Saima; Kim, Gunjune; Johnson, Nathan R; Wafula, Eric; Wang, Feng; Coruh, Ceyda; Bernal-Galeano, Vivian; Phifer, Tamia; dePamphilis, Claude W; Westwood, James H; Axtell, Michael J

2018-01-03

Dodders (Cuscuta spp.) are obligate parasitic plants that obtain water and nutrients from the stems of host plants via specialized feeding structures called haustoria. Dodder haustoria facilitate bidirectional movement of viruses, proteins and mRNAs between host and parasite, but the functional effects of these movements are not known. Here we show that Cuscuta campestris haustoria accumulate high levels of many novel microRNAs (miRNAs) while parasitizing Arabidopsis thaliana. Many of these miRNAs are 22 nucleotides in length. Plant miRNAs of this length are uncommon, and are associated with amplification of target silencing through secondary short interfering RNA (siRNA) production. Several A. thaliana mRNAs are targeted by 22-nucleotide C. campestris miRNAs during parasitism, resulting in mRNA cleavage, secondary siRNA production, and decreased mRNA accumulation. Hosts with mutations in two of the loci that encode target mRNAs supported significantly higher growth of C. campestris. The same miRNAs that are expressed and active when C. campestris parasitizes A. thaliana are also expressed and active when it infects Nicotiana benthamiana. Homologues of target mRNAs from many other plant species also contain the predicted target sites for the induced C. campestris miRNAs. These data show that C. campestris miRNAs act as trans-species regulators of host-gene expression, and suggest that they may act as virulence factors during parasitism.

Emerging RNA-based drugs: siRNAs, microRNAs and derivates.

Science.gov (United States)

Pereira, Tiago Campos; Lopes-Cendes, Iscia

2012-09-01

An emerging new category of therapeutic agents based on ribonucleic acid has emerged and shown very promising in vitro, animal and pre-clinical results, known as small interfering RNAs (siRNAs), microRNAs mimics (miRNA mimics) and their derivates. siRNAs are small RNA molecules that promote potent and specific silencing of mutant, exogenous or aberrant genes through a mechanism known as RNA interference. These agents have called special attention to medicine since they have been used to experimentally treat a series of neurological conditions with distinct etiologies such as prion, viral, bacterial, fungal, genetic disorders and others. siRNAs have also been tested in other scenarios such as: control of anxiety, alcohol consumption, drug-receptor blockage and inhibition of pain signaling. Although in a much earlier stage, miRNAs mimics, anti-miRs and small activating RNAs (saRNAs) also promise novel therapeutic approaches to control gene expression. In this review we intend to introduce clinicians and medical researchers to the most recent advances in the world of siRNA- and miRNA-mediated gene control, its history, applications in cells, animals and humans, delivery methods (an yet unsolved hurdle), current status and possible applications in future clinical practice.

SiRNAs conjugated with aromatic compounds induce RISC-mediated antisense strand selection and strong gene-silencing activity

Energy Technology Data Exchange (ETDEWEB)

Kubo, Takanori, E-mail: kubo-t@yasuda-u.ac.jp [Faculty of Pharmacy, Yasuda Women' s University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153 (Japan); Yanagihara, Kazuyoshi [Faculty of Pharmacy, Yasuda Women' s University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153 (Japan); Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Takei, Yoshifumi [Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumi-cho, Showa-ku, Nagoya 466-8550 (Japan); Mihara, Keichiro [Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan); Sato, Yuichiro; Seyama, Toshio [Faculty of Pharmacy, Yasuda Women' s University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153 (Japan)

2012-10-05

Highlights: Black-Right-Pointing-Pointer SiRNAs conjugated with aromatic compounds (Ar-siRNAs) at 5 Prime -sense strand were synthesized. Black-Right-Pointing-Pointer Ar-siRNAs increased resistance against nuclease degradation. Black-Right-Pointing-Pointer Ar-siRNAs were thermodynamically stable compared with the unmodified siRNA. Black-Right-Pointing-Pointer High levels of cellular uptake and cytoplasmic localization were found. Black-Right-Pointing-Pointer Strong gene-silencing efficacy was exhibited in the Ar-siRNAs. -- Abstract: Short interference RNA (siRNA) is a powerful tool for suppressing gene expression in mammalian cells. In this study, we focused on the development of siRNAs conjugated with aromatic compounds in order to improve the potency of RNAi and thus to overcome several problems with siRNAs, such as cellular delivery and nuclease stability. The siRNAs conjugated with phenyl, hydroxyphenyl, naphthyl, and pyrenyl derivatives showed strong resistance to nuclease degradation, and were thermodynamically stable compared with unmodified siRNA. A high level of membrane permeability in HeLa cells was also observed. Moreover, these siRNAs exhibited enhanced RNAi efficacy, which exceeded that of locked nucleic acid (LNA)-modified siRNAs, against exogenous Renilla luciferase in HeLa cells. In particular, abundant cytoplasmic localization and strong gene-silencing efficacy were found in the siRNAs conjugated with phenyl and hydroxyphenyl derivatives. The novel siRNAs conjugated with aromatic compounds are promising candidates for a new generation of modified siRNAs that can solve many of the problems associated with RNAi technology.

Individual microRNAs (miRNAs) display distinct mRNA targeting "rules".

Science.gov (United States)

Wang, Wang-Xia; Wilfred, Bernard R; Xie, Kevin; Jennings, Mary H; Hu, Yanling Hu; Stromberg, Arnold J; Nelson, Peter T

2010-01-01

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using an assay we validated previously-a "RIP-Chip" experimental design. RIP-Chip data provided a list of mRNAs recruited into the AGO-miRNP in correlation to each miRNA. These experimentally identified miRNA targets were analyzed for complementary six nucleotide "seed" sequences within the transfected miRNAs. We found that miR-124 targets tended to have sequences in the 3'UTR that would be recognized by the 5' seed of miR-124, as described in previous studies. By contrast, miR-107 targets tended to have 'seed' sequences in the mRNA open reading frame, but not the 3' UTR. Further, mRNA targets of miR-128 and miR-320 are less enriched for 6-mer seed sequences in comparison to miR-107 and miR-124. In sum, our data support the importance of the 5' seed in determining binding characteristics for some miRNAs; however, the "binding rules" are complex, and individual miRNAs can have distinct sequence determinants that lead to mRNA targeting.

MenA Is a Promising Drug Target for Developing Novel Lead Molecules to Combat Mycobacterium tuberculosis

OpenAIRE

Kurosu, Michio; Crick, Dean C.

2009-01-01

Potent inhibitors of MenA (1,4-dihydroxy-2-naphtoate prenyltrasferase) in Mycobacterium tuberculosis are identified, and are also effective in inhibiting growth of Mycobacterium tuberculosis at low concentrations. The MenA inhibitors possess common chemical structural features of ((alkylamino)alkoxyphenyl)(phenyl)methanones. Significantly, the MenA inhibitors can be synthesized in a few steps with high overall yields. The representative MenA inhibitors are highly effective in killing nonrepli...

Differential MicroRNA Expression in Human Macrophages with Mycobacterium tuberculosis Infection of Beijing/W and Non-Beijing/W Strain Types.

Science.gov (United States)

Zheng, Lin; Leung, Eric; Lee, Nelson; Lui, Grace; To, Ka-Fai; Chan, Raphael C Y; Ip, Margaret

2015-01-01

The role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls. The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (PmicroRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems. We showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections.

deepBase v2.0: identification, expression, evolution and function of small RNAs, LncRNAs and circular RNAs from deep-sequencing data.

Science.gov (United States)

Zheng, Ling-Ling; Li, Jun-Hao; Wu, Jie; Sun, Wen-Ju; Liu, Shun; Wang, Ze-Lin; Zhou, Hui; Yang, Jian-Hua; Qu, Liang-Hu

2016-01-04

Small non-coding RNAs (e.g. miRNAs) and long non-coding RNAs (e.g. lincRNAs and circRNAs) are emerging as key regulators of various cellular processes. However, only a very small fraction of these enigmatic RNAs have been well functionally characterized. In this study, we describe deepBase v2.0 (http://biocenter.sysu.edu.cn/deepBase/), an updated platform, to decode evolution, expression patterns and functions of diverse ncRNAs across 19 species. deepBase v2.0 has been updated to provide the most comprehensive collection of ncRNA-derived small RNAs generated from 588 sRNA-Seq datasets. Moreover, we developed a pipeline named lncSeeker to identify 176 680 high-confidence lncRNAs from 14 species. Temporal and spatial expression patterns of various ncRNAs were profiled. We identified approximately 24 280 primate-specific, 5193 rodent-specific lncRNAs, and 55 highly conserved lncRNA orthologs between human and zebrafish. We annotated 14 867 human circRNAs, 1260 of which are orthologous to mouse circRNAs. By combining expression profiles and functional genomic annotations, we developed lncFunction web-server to predict the function of lncRNAs based on protein-lncRNA co-expression networks. This study is expected to provide considerable resources to facilitate future experimental studies and to uncover ncRNA functions. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pluripotent State Induction in Mouse Embryonic Fibroblast Using mRNAs of Reprogramming Factors

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Ahmed Kamel El-Sayed

2014-11-01

Full Text Available Reprogramming of somatic cells has great potential to provide therapeutic treatments for a number of diseases as well as provide insight into mechanisms underlying early embryonic development. Improvement of induced Pluripotent Stem Cells (iPSCs generation through mRNA-based methods is currently an area of intense research. This approach provides a number of advantages over previously used methods such as DNA integration and insertional mutagenesis. Using transfection of specifically synthesized mRNAs of various pluripotency factors, we generated iPSCs from mouse embryonic fibroblast (MEF cells. The genetic, epigenetic and functional properties of the iPSCs were evaluated at different times during the reprogramming process. We successfully introduced synthesized mRNAs, which localized correctly inside the cells and exhibited efficient and stable translation into proteins. Our work demonstrated a robust up-regulation and a gradual promoter de-methylation of the pluripotency markers, including non-transfected factors such as Nanog, SSEA-1 (stage-specific embryonic antigen 1 and Rex-1 (ZFP-42, zinc finger protein 42. Using embryonic stem cells (ESCs conditions to culture the iPS cells resulted in formation of ES-like colonies after approximately 12 days with only five daily repeated transfections. The colonies were positive for alkaline phosphatase and pluripotency-specific markers associated with ESCs. This study revealed the ability of pluripotency induction and generation of mouse mRNA induced pluripotent stem cells (mRNA iPSCs using transfection of specifically synthesized mRNAs of various pluripotency factors into mouse embryonic fibroblast (MEF cells. These generated iPSCs exhibited molecular and functional properties similar to ESCs, which indicate that this method is an efficient and viable alternative to ESCs and can be used for further biological, developmental and therapeutic investigations.

Embryonic chicken cornea and cartilage synthesize type IX collagen molecules with different amino-terminal domains.

OpenAIRE

Svoboda, K K; Nishimura, I; Sugrue, S P; Ninomiya, Y; Olsen, B R

1988-01-01

We have analyzed embryonic chicken cornea for the presence of type IX collagen mRNA and protein. Using RNA transfer blot analysis, we demonstrate that alpha 1(IX) and alpha 2(IX) mRNAs are expressed by corneal epithelial cells at the time that the primary stromal components are synthesized. The levels of the mRNAs decrease with increasing developmental age and are barely detectable at day 11 of development. In contrast, type IX collagen protein is detectable by immunofluorescence at days 5 an...

Integrative analysis of circRNAs acting as ceRNAs involved in ethylene pathway in tomato.

Science.gov (United States)

Wang, Yunxiang; Wang, Qing; Gao, Lipu; Zhu, Benzhong; Luo, Yunbo; Deng, Zhiping; Zuo, Jinhua

2017-11-01

Circular RNAs (circRNAs) are a large class of non-coding endogenous RNAs that could act as competing endogenous RNAs (ceRNAs) to terminate the mRNA targets' suppression of miRNAs. To elucidate the intricate regulatory roles of circRNAs in the ethylene pathway in tomato fruit, deep sequencing and bioinformatics methods were performed. After strict screening, a total of 318 circRNAs were identified. Among these circRNAs, 282 were significantly differentially expressed among wild-type and sense-/antisense-LeERF1 transgenic tomato fruits. Besides, 1254 target genes were identified and a large amount of them were found to be involved in ethylene pathway. In addition, a sophisticated regulatory model consisting of circRNAs, target genes and ethylene was set up. Importantly, 61 circRNAs were found to be potential ceRNAs to combine with miRNAs and some of the miRNAs had been revealed to participate in the ethylene signaling pathway. This research further raised the possibility that the ethylene pathway in tomato fruit may be under the regulation of various circRNAs and provided a new perspective of the roles of circRNAs. © 2017 Scandinavian Plant Physiology Society.

Role of miRNAs and siRNAs in biotic and abiotic stress responses of plants

KAUST Repository

Khraiwesh, Basel

2012-02-01

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. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress. © 2011 Elsevier B.V.

Visual screening for localized RNAs in yeast revealed novel RNAs at the bud-tip

International Nuclear Information System (INIS)

Andoh, Tomoko; Oshiro, Yukiko; Hayashi, Sachiko; Takeo, Hideki; Tani, Tokio

2006-01-01

Several RNAs, including rRNAs, snRNAs, snoRNAs, and some mRNAs, are known to be localized at specific sites in a cell. Although methods have been established to visualize RNAs in a living cell, no large-scale visual screening of localized RNAs has been performed. In this study, we constructed a genomic library in which random genomic fragments were inserted downstream of U1A-tag sequences under a GAL1 promoter. In a living yeast cell, transcribed U1A-tagged RNAs were visualized by U1A-GFP that binds the RNA sequence of the U1A-tag. In this screening, many RNAs showed nuclear signals. Since the nuclear signals of some RNAs were not seen when the U1A-tag was connected to the 3' ends of the RNAs, it is suggested that their nuclear signals correspond to nascent transcripts on GAL1 promoter plasmids. Using this screening method, we successfully identified two novel localized mRNAs, CSR2 and DAL81, which showed bud-tip localization

Non-Coding RNAs and Endometrial Cancer

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Cristina Vallone

2018-03-01

Full Text Available Non-coding RNAs (ncRNAs are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs has also been included in cancer studies. Studies on the relation between endometrial cancer (EC and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs, transfer RNAs (tRNAs, ribosomal RNAs (rRNAs, antisense RNAs (asRNAs, small nuclear RNAs (snRNAs, Piwi-interacting RNAs (piRNAs, small nucleolar RNAs (snoRNAs, competing endogenous RNAs (ceRNAs, lncRNAs, and long intergenic ncRNAs (lincRNAs have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.

Managing latent tuberculosis infection and tuberculosis in children

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I. Carvalho

2018-03-01

Full Text Available Tuberculosis (TB is a major cause of childhood morbidity and mortality worldwide. The aim of this review is to describe the management of the child with TB and latent tuberculosis infection (LTBI.To develop this article, a working group reviewed relevant epidemiological and other scientific studies and established practices in conducting LBTI and TB in children. The article describes how to manage the child with LTBI, considering transmission and infectiousness of tuberculosis, contact screening and prioritization of contacts and recommendations on treatment of children with LTBI and how to manage the child with TB considering the susceptibility of children to developing tuberculosis, epidemiology and classification of tuberculosis in children, diagnosis and treatment. Keywords: Tuberculosis, Pediatric, Childhood, Latent tuberculosis infection

Tuberculosis

International Nuclear Information System (INIS)

Latorre Tortello, Pablo

1998-01-01

The tuberculosis is an infection bacterial chronicle of world distribution. Three organisms of the family of the mycobacterium, the m. tuberculosis, the m. bovis and m. africanum, phenotypic and genetically similar, produce it, but only the m. tuberculosis has importance; the others rarely produce illness in the human. By definition, the lung tuberculosis is the localization of the m. tuberculosis in the breathing tract, the most common and main form in the affection and the only able to contaminate to other people. The koch bacillus, transmits the illness directly person to person. The paper Includes topics like pathogenesis, natural history, epidemiology, diagnose, symptomatology and treatment

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Science.gov (United States)

Naderi, Elnaz; Mostafaei, Mehdi; Pourshams, Akram

2014-01-01

Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches. PMID:24895587

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Elnaz Naderi

2014-01-01

Full Text Available Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches.

Analysis of transcription factors, microRNAs and cytokines involved in T lymphocyte differentiation in patients with tuberculosis after directly observed treatment short-course.

Science.gov (United States)

Corral-Fernández, Nancy Elizabeth; Cortes-García, Juan Diego; Bruno, Rivas-Santiago; Romano-Moreno, Silvia; Medellín-Garibay, Susanna E; Magaña-Aquino, Martín; Salazar-González, Raúl A; González-Amaro, Roberto; Portales-Pérez, Diana Patricia

2017-07-01

Tuberculosis (Tb) is an infectious disease in which the immune system plays an important role. MicroRNAs are involved in the development and maintenance of CD4 + T lymphocyte subpopulations. miR-326 regulates the differentiation to Th17 cells and miR-29 correlates with the Th1 response. The aim of this study was to determine the role of microRNAs, Transcription Factors, and cytokines in Th differentiation before and after the directly observed treatment short-course (DOTS). Peripheral blood mononuclear cells and serum from Tb patients were collected at times 0 (before therapy), 2 (after the intensive phase), and 6 months (after the holding phase). The cells were cultivated in presence or absence of ESAT-6 (10 μg/ml) and CFP-10 (10 μg/ml). Transcription Factor and microRNA expressions were analyzed by qPCR and cytokine production in both serum and culture supernatant using ELISA. A decrease in Th1 response with a diminishing in the relative expression of TBET and miR-29a at 2 and 6 months after the anti-Tb therapy (p < 0.01) were found. The miR-326 levels decreased after the intensive phase of the DOTS scheme. However, subdivision of the Tb patients according to gender, showed increased levels of miR-29a and miR-155 in females after the intensive phase of the therapeutic treatment when compared to time 0 and similar increased levels of miR-326 at time 6 versus time 0. In contrast, we observed a decrease in miR-326 levels in males at 6 months when compared to before therapy (time 0). In addition, high production of IL-17 in the culture supernatant was found at 2 and 6 months (p < 0.05) while in serum IL-17 was decreased. A positive correlation between IL-17 and RORC2 at time 6 was detected (p = 0.0202, r = 0.7880). In conclusion, these data suggest a reduction in Th1 and an induction of Th17 response after the anti-Tb therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tuberculosis

OpenAIRE

Mochammad, Hatta

2008-01-01

This book chapter for medical students and researcher Tuberculosis is still one of the leading causes of death by infectious diseases with 2 million deaths per year and 9.2 million new cases of tuberculosis disease annually [1-3]. Besides, more than 2 milliard people are infected with latent tuberculosis infection (LTBI) [1-3]. Despite continuous effort in the prevention, monitoring and treatment of tuberculosis, the disease remains a major health problem in many countries [4-6...

Differential MicroRNA Expression in Human Macrophages with Mycobacterium tuberculosis Infection of Beijing/W and Non-Beijing/W Strain Types.

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Lin Zheng

Full Text Available The role of microRNAs in association with Mycobacterium tuberculosis (MTB infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI, and from healthy controls.The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P<0.05. A unique signature of 11 microRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems.We showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections.

Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum

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Wang Heng

2010-01-01

Full Text Available Abstract Background Small endogenous non-coding RNAs (sncRNAs such as small interfering RNA (siRNA, microRNA and other small RNA transcripts are derived from distinct loci in the genome and play critical roles in RNA-mediated gene silencing mechanisms in plants and metazoa. They are approximately 22 nucleotides long; regulate mRNA stability through perfect or imperfect match to the targets. The biological activities of sncRNAs have been related to many biological events, from resistance to microbe infections to cellular differentiation. The development of the zoonotic parasite Schistosoma japonicum parasite includes multiple steps of morphological alterations and biological differentiations, which provide a unique model for studies on the functions of small RNAs. Characterization of the genome-wide transcription of the sncRNAs will be a major step in understanding of the parasite biology. The objective of this study is to investigate the transcriptional profile and potential function of the small non-coding RNAs in the development of S. japanicum. Results The endogenous siRNAs were found mainly derived from transposable elements (TE or transposons and the natural antisense transcripts (NAT. In contrast to other organisms, the TE-derived siRNAs in S. japonicum were more predominant than other sncRNAs including microRNAs (miRNAs. Further, there were distinct length and 3'end variations in the sncRNAs, which were associated with the developmental differentiation of the parasite. Among the identified miRNA transcripts, there were 38 unique to S. japonicum and 16 that belonged to 13 miRNA families are common to other metazoan lineages. These miRNAs were either ubiquitously expressed, or they exhibited specific expression patterns related to the developmental stages or sex. Genes that encoded miRNAs are mainly located in clusters within the genome of S. japonicum. However, genes within one cluster could be differentially transcribed, which suggested

Isolation and Identification of Post-Transcriptional Gene Silencing-Related Micro-RNAs by Functionalized Silicon Nanowire Field-effect Transistor

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Chen, Kuan-I.; Pan, Chien-Yuan; Li, Keng-Hui; Huang, Ying-Chih; Lu, Chia-Wei; Tang, Chuan-Yi; Su, Ya-Wen; Tseng, Ling-Wei; Tseng, Kun-Chang; Lin, Chi-Yun; Chen, Chii-Dong; Lin, Shih-Shun; Chen, Yit-Tsong

2015-11-01

Many transcribed RNAs are non-coding RNAs, including microRNAs (miRNAs), which bind to complementary sequences on messenger RNAs to regulate the translation efficacy. Therefore, identifying the miRNAs expressed in cells/organisms aids in understanding genetic control in cells/organisms. In this report, we determined the binding of oligonucleotides to a receptor-modified silicon nanowire field-effect transistor (SiNW-FET) by monitoring the changes in conductance of the SiNW-FET. We first modified a SiNW-FET with a DNA probe to directly and selectively detect the complementary miRNA in cell lysates. This SiNW-FET device has 7-fold higher sensitivity than reverse transcription-quantitative polymerase chain reaction in detecting the corresponding miRNA. Next, we anchored viral p19 proteins, which bind the double-strand small RNAs (ds-sRNAs), on the SiNW-FET. By perfusing the device with synthesized ds-sRNAs of different pairing statuses, the dissociation constants revealed that the nucleotides at the 3‧-overhangs and pairings at the terminus are important for the interactions. After perfusing the total RNA mixture extracted from Nicotiana benthamiana across the device, this device could enrich the ds-sRNAs for sequence analysis. Finally, this bionanoelectronic SiNW-FET, which is able to isolate and identify the interacting protein-RNA, adds an additional tool in genomic technology for the future study of direct biomolecular interactions.

Tuberculosis.

Science.gov (United States)

Tabbara, Khalid F

2007-11-01

The purpose of this report is to present an update on the manifestations and management of ocular tuberculosis. Tuberculosis affects one-third of the world's population. The incidence of tuberculosis has increased with the increase in the HIV infected population. Following a resurgence of the disease in the US, the incidence has recently declined. Patients may develop scleritis that can be focal, nodular or diffuse with or without keratitis. Anterior granulomatous uveitis may occur. The posterior segment reveals vitritis, choroiditis, and can mimic serpiginous choroiditis and other entities. Patients who are immunosuppressed or HIV infected may develop active mycobacterial disease in the eye leading to rapid destruction of the ocular structures. The diagnosis of ocular tuberculosis is made by isolation of Mycobacterium tuberculosis on Löwestein-Jensen medium or by PCR. The diagnosis is supported by the clinical findings, imaging techniques including optical coherence tomography, fluorescein angiography, indocyanine green and ultrasonography. Tuberculin skin test helps to confirm the diagnosis. Ocular tuberculosis may occur in the absence of pulmonary disease. Patients present with a spectrum of clinical signs. The disease may mimic several clinical entities. Early diagnosis and prompt treatment of ocular tuberculosis may prevent ocular morbidity and blindness.

Integrative analysis of lncRNAs and miRNAs with coding RNAs associated with ceRNA crosstalk network in triple negative breast cancer

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Yuan NJ

2017-12-01

Full Text Available Naijun Yuan,1,* Guijuan Zhang,2,* Fengjie Bie,1 Min Ma,1 Yi Ma,3 Xuefeng Jiang,1 Yurong Wang,1,* Xiaoqian Hao1 1College of Traditional Chinese Medicine of Jinan University, Institute of Integrated Traditional Chinese and Western Medicine of Jinan University, 2The First Affiliated Hospital of Jinan University, 3Department of Cellular Biology, Guangdong Province Key Lab of Bioengineering Medicine, Institute of Biomedicine, Jinan University, Guangdong, China *These authors contributed equally to this work Abstract: Triple negative breast cancer (TNBC is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Currently, there is increasing focus on long non-coding RNAs (lncRNAs, which can act as competing endogenous RNAs (ceRNAs and suppress miRNA functions involved in post-transcriptional regulatory networks in the tumor. Therefore, to investigate specific mechanisms of TNBC carcinogenesis and improve treatment efficiency, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 116 TNBC tissues and 11 normal tissues from The Cancer Genome Atlas. As a result, we selected the threshold with |log2FC|>2.0 and an adjusted p-value >0.05 to obtain the differentially expressed mRNAs, miRNAs and lncRNAs. Hereafter, weighted gene co-expression network analysis was performed to identify the expression characteristics of dysregulated genes. We obtained five co-expression modules and related clinical feature. By means of correlating gene modules with protein–protein interaction network analysis that had identified 22 hub mRNAs which could as hub target genes. Eleven key dysregulated differentially expressed micro RNAs (DEmiRNAs were identified that were significantly associated with the 22 hub potential target genes. Moreover, we found that 14 key differentially expressed lncRNAs could interact with the key DEmiRNAs. Then, the ceRNA crosstalk network of TNBC was

Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2

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De, Nabanita; Young, Lisa; Lau, Pick-Wei; Meisner, Nicole-Claudia; Morrissey, David V.; MacRae, Ian J.

2013-01-01

SUMMARY Argonaute proteins use small RNAs to guide the silencing of complementary target RNAs in many eukaryotes. Although small RNA biogenesis pathways are well studied, mechanisms for removal of guide RNAs from Argonaute are poorly understood. Here we show that the Argonaute2 (Ago2) guide RNA complex is extremely stable, with a half-life on the order of days. However, highly complementary target RNAs destabilize the complex and significantly accelerate release of the guide RNA from Ago2. This “unloading” activity can be enhanced by mismatches between the target and the guide 5′ end and attenuated by mismatches to the guide 3′ end. The introduction of 3′ mismatches leads to more potent silencing of abundant mRNAs in mammalian cells. These findings help to explain why the 3′ ends of mammalian microRNAs (miRNAs) rarely match their targets, suggest a mechanism for sequence-specific small RNA turnover, and offer insights for controlling small RNAs in mammalian cells. PMID:23664376

Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

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Barik, Sailen

2009-01-01

Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

Tuberculosis

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Elena Morán López

2001-04-01

Full Text Available En la actualidad la incidencia de la tuberculosis ha aumentado. El Mycobacterium tuberculosis infecta frecuentemente a las personas con SIDA, debido a que en estos pacientes hay una reducción de la resistencia mediada por células T, lo que propicia que este bacilo pueda desarrollar la enfermedad con una frecuencia superior a la de las personas sanas. La transmisión de la enfermedad puede ser por vía directa, de un individuo afectado a otro, fundamentalmente por las gotitas de saliva que contengan a este microorganismo, o por vía indirecta por la inhalación del bacilo que se puede encontrar por meses en los objetos de uso diario, debido a su gran resistencia. Las micobacterias que producen tuberculosis en el hombre inmunocompetente son la Mycobacterium tuberculosis y la bovis, otros tipos pueden provocar tuberculosis en individuos inmunocomprometidos. La patogenicidad de este bacilo está relacionada con su capacidad para escapar de la destrucción inducida por los macrófagos y para provocar hipersensibilidad de tipo retardado. Esta enfermedad tiene muy pocas manifestaciones bucales, lo que se observa generalmente es una úlcera que toma como asiento fundamental el dorso de la lengua. La tuberculosis amenaza con convertirse en una enfermedad incurable por la deficiente administración de los programas contra ésta, por lo que la OMS plantea para su detección y tratamiento el DOTS (tratamiento observado directamente, de corta duración que comienza a tener resultados satisfactorios, aunque en el último quinquenio, el 88 % de los pacientes que se estimaban como infectados por tuberculosis no recibieron DOTS.At present, the incidence of tuberculosis is on the rise. Mycobacterium tuberculosis often infests AIDS patients due to the fact that these persons´T-cell mediated resistance is reduced, which favors the development of the disease at a higher rate than in healthy people. The disease can be transmitted directly, that is , from an

Renal tuberculosis

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Džamić Zoran

2016-01-01

Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

Tuberculosis (TB): Treatment

Science.gov (United States)

... Education & Training Home Conditions Tuberculosis (TB) Tuberculosis: Treatment Tuberculosis: Treatment Make an Appointment Refer a Patient Ask ... or bones is treated longer. NEXT: Preventive Treatment Tuberculosis: Diagnosis Tuberculosis: History Clinical Trials For more than ...

Living with Tuberculosis

Science.gov (United States)

... Diseases > Lung Disease Lookup > Tuberculosis (TB) Living With Tuberculosis What to Expect You will need regular checkups ... XML file."); } }); } } --> Blank Section Header Lung Disease Lookup Tuberculosis (TB) Learn About Tuberculosis Tuberculosis Symptoms, Causes & Risk ...

Micro RNAs in animal development.

NARCIS (Netherlands)

Plasterk, R.H.A.

2006-01-01

Micro RNAs (miRNAs) are approximately 22 nucleotide single-stranded noncoding RNA molecules that bind to target messenger RNAs (mRNAs) and silence their expression. This Essay explores the importance of miRNAs in animal development and their possible roles in disease and evolution.

Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging.

Science.gov (United States)

Grammatikakis, Ioannis; Panda, Amaresh C; Abdelmohsen, Kotb; Gorospe, Myriam

2014-12-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits.

Progress and Prospects of Long Noncoding RNAs (lncRNAs in Hepatocellular Carcinoma

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Chen Li

2015-05-01

Full Text Available Hepatocellular carcinoma (HCC is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional “noise” to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC.

Tuberculosis como enfermedad ocupacional Tuberculosis as occupational disease

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Alberto Mendoza-Ticona

2012-06-01

Full Text Available Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto.There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupational disease among health care workers, presenting the current Peruvian law related.

Utility of MicroRNAs and siRNAs in Cervical Carcinogenesis

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Sacnite del Mar Díaz-González

2015-01-01

Full Text Available MicroRNAs and siRNAs belong to a family of small noncoding RNAs which bind through partial sequence complementarity to 3′-UTR regions of mRNA from target genes, resulting in the regulation of gene expression. MicroRNAs have become an attractive target for genetic and pharmacological modulation due to the critical function of their target proteins in several signaling pathways, and their expression profiles have been found to be altered in various cancers. A promising technology platform for selective silencing of cell and/or viral gene expression using siRNAs is currently in development. Cervical cancer is the most common cancer in women in the developing world and sexually transmitted infection with HPV is the cause of this malignancy. Therefore, a cascade of abnormal events is induced during cervical carcinogenesis, including the induction of genomic instability, reprogramming of cellular metabolic pathways, deregulation of cell proliferation, inhibition of apoptotic mechanisms, disruption of cell cycle control mechanisms, and alteration of gene expression. Thus, in the present review article, we highlight new research on microRNA expression profiles which may be utilized as biomarkers for cervical cancer. Furthermore, we discuss selective silencing of HPV E6 and E7 with siRNAs which represents a potential gene therapy strategy against cervical cancer.

Transposon defense by endo-siRNAs, piRNAs and somatic pilRNAs in Drosophila: contributions of Loqs-PD and R2D2.

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Milijana Mirkovic-Hösle

Full Text Available Transposable elements are a serious threat for genome integrity and their control via small RNA mediated silencing pathways is an ancient strategy. The fruit fly Drosophila melanogaster has two silencing activities that target transposons: endogenous siRNAs (esiRNAs or endo-siRNAs and Piwi-interacting small RNAs (piRNAs. The biogenesis of endo-siRNAs involves the Dicer-2 co-factors Loqs-PD, which acts predominantly during processing of dsRNA by Dcr-2, and R2D2, which primarily helps to direct siRNAs into the RNA interference effector Ago2. Nonetheless, loss of either protein is not sufficient to produce a phenotype comparable with a dcr-2 mutation. We provide further deep sequencing evidence supporting the notion that R2D2 and Loqs-PD have partially overlapping function. Certain transposons display a preference for either dsRBD-protein during production or loading; this appeared to correlate neither with overall abundance, classification of the transposon or a specific site of genomic origin. The endo-siRNA biogenesis pathway in germline operates according to the same principles as the existing model for the soma, and its impairment does not significantly affect piRNAs. Expanding the analysis, we confirmed the occurrence of somatic piRNA-like RNAs (pilRNAs that show a ping-pong signature. We detected expression of the Piwi-family protein mRNAs only barely above background, indicating that the somatic pilRNAs may arise from a small sub-population of somatic cells that express a functional piRNA pathway.

Colorectal tuberculosis

International Nuclear Information System (INIS)

Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.

2003-01-01

Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

Tuberculosis

Science.gov (United States)

Friend, Milton

1999-01-01

Avian tuberculosis is usually caused by the bacterium Mycobacterium avium. At least 20 different types of M. avium have been identified, only three of which are known to cause disease in birds. Other types of Mycobacterium rarely cause tuberculosis in most avian species; however, parrots, macaws, and other large perching birds are susceptible to human and bovine types of tuberculosis bacilli. Avian tuberculosis generally is transmitted by direct contact with infected birds, ingestion of contaminated feed and water, or contact with a contaminated environment. Inhalation of the bacterium can cause respiratory tract infections. Wild bird studies in the Netherlands disclosed tuberculosis-infected puncture-type injuries in birds of prey that fight at the nest site (kestrels) or on the ground (buteo-type buzzards), but tuberculosisinfected injuries were not found in accipiters (falco

miRNAs in brain development

International Nuclear Information System (INIS)

Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

2014-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function

Circular RNAs and systemic lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Li, Lian-Ju; Huang, Qing; Pan, Hai-Feng; Ye, Dong-Qing, E-mail: ydqahmu@gmail.com

2016-08-15

Circular RNAs (circRNAs) are a large class of noncoding RNAs that form covalently closed RNA circles. The discovery of circRNAs discloses a new layer of gene regulation occurred post-transcriptionally. Identification of endogenous circRNAs benefits from the advance in high-throughput RNA sequencing and remains challenging. Many studies probing into the mechanisms of circRNAs formation occurred cotranscriptionally or posttranscriptionally emerge and conclude that canonical splicing mechanism, sequence properties, and certain regulatory factors are at play in the process. Although our knowledge on functions of circRNAs is rather limited, a few circRNAs are shown to sponge miRNA and regulate gene transcription. The clearest case is one circRNA CDR1as that serves as sponge of miR-7. Researches on circRNAs in human diseases such as cancers highlight the function and physical relevance of circRNAs. Given the implication of miRNAs in the initiation and progression of systemic lupus erythematosus (SLE) and the roles of circRNAs in sponging miRNA and gene regulation, it is appealing to speculate that circRNAs may associate with SLE and may be potential therapeutic targets for treatment of SLE. Future studies should attach more importance to the relationship between circRNAs and SLE. This review will concern identification, biogenesis, and function of circRNAs, introduce reports exploring the association of circRNAs with human diseases, and conjecture the potential roles of circRNAs in SLE. - Highlights: • Studies have discovered thousands of circRNAs and interpreted their biogenesis. • Cytoplasmic circRNAs sponge miRNA and nuclear circRNAs modulate gene transcription. • Aberrant expression of circRNAs has been observed in various cancers. • CircRNAs may partake in the pathogenesis of systemic lupus erythematosus.

Circular RNAs and systemic lupus erythematosus

International Nuclear Information System (INIS)

Li, Lian-Ju; Huang, Qing; Pan, Hai-Feng; Ye, Dong-Qing

2016-01-01

Circular RNAs (circRNAs) are a large class of noncoding RNAs that form covalently closed RNA circles. The discovery of circRNAs discloses a new layer of gene regulation occurred post-transcriptionally. Identification of endogenous circRNAs benefits from the advance in high-throughput RNA sequencing and remains challenging. Many studies probing into the mechanisms of circRNAs formation occurred cotranscriptionally or posttranscriptionally emerge and conclude that canonical splicing mechanism, sequence properties, and certain regulatory factors are at play in the process. Although our knowledge on functions of circRNAs is rather limited, a few circRNAs are shown to sponge miRNA and regulate gene transcription. The clearest case is one circRNA CDR1as that serves as sponge of miR-7. Researches on circRNAs in human diseases such as cancers highlight the function and physical relevance of circRNAs. Given the implication of miRNAs in the initiation and progression of systemic lupus erythematosus (SLE) and the roles of circRNAs in sponging miRNA and gene regulation, it is appealing to speculate that circRNAs may associate with SLE and may be potential therapeutic targets for treatment of SLE. Future studies should attach more importance to the relationship between circRNAs and SLE. This review will concern identification, biogenesis, and function of circRNAs, introduce reports exploring the association of circRNAs with human diseases, and conjecture the potential roles of circRNAs in SLE. - Highlights: • Studies have discovered thousands of circRNAs and interpreted their biogenesis. • Cytoplasmic circRNAs sponge miRNA and nuclear circRNAs modulate gene transcription. • Aberrant expression of circRNAs has been observed in various cancers. • CircRNAs may partake in the pathogenesis of systemic lupus erythematosus.

C. elegans microRNAs.

Science.gov (United States)

Vella, Monica C; Slack, Frank J

2005-09-21

MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in human cancers. The C. elegans genome encodes hundreds of miRNAs, including the founding members of the miRNA family lin-4 and let-7. Despite the abundance of C. elegans miRNAs, few miRNA targets are known and little is known about the mechanism by which they function. However, C. elegans research continues to push the boundaries of discovery in this area. lin-4 and let-7 are the best understood miRNAs. They control the timing of adult cell fate determination in hypodermal cells by binding to partially complementary sites in the mRNA of key developmental regulators to repress protein expression. For example, lin-4 is predicted to bind to seven sites in the lin-14 3' untranslated region (UTR) to repress LIN-14, while let-7 is predicted to bind two let-7 complementary sites in the lin-41 3' UTR to down-regulate LIN-41. Two other miRNAs, lsy-6 and mir-273, control left-right asymmetry in neural development, and also target key developmental regulators for repression. Approximately one third of the C. elegans miRNAs are differentially expressed during development indicating a major role for miRNAs in C. elegans development. Given the remarkable conservation of developmental mechanism across phylogeny, many of the principles of miRNAs discovered in C. elegans are likely to be applicable to higher animals.

MicroRNAs, Regulatory Networks, and Comorbidities

DEFF Research Database (Denmark)

Russo, Francesco; Belling, Kirstine; Jensen, Anders Boeck

2017-01-01

MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of messenger RNAs (mRNAs). Each miRNA targets a specific set of mRNAs. Upon binding the miRNA inhibits mRNA translation or facilitate mRNA degradation. miRNAs are frequently deregulated in several pathologies...

Identifying small RNAs derived from maternal- and somatic-type rRNAs in zebrafish development.

Science.gov (United States)

Locati, Mauro D; Pagano, Johanna F B; Abdullah, Farah; Ensink, Wim A; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Spaink, Herman P; Rauwerda, Han; Jonker, Martijs J; Dekker, Rob J; Breit, Timo M

2018-02-09

rRNAs are non-coding RNAs present in all prokaryotes and eukaryotes. In eukaryotes there are four rRNAs: 18S, 5.8S, 28S, originating from a common precursor (45S), and 5S. We have recently discovered the existence of two distinct developmental types of rRNA: a maternal-type, present in eggs and a somatic-type, expressed in adult tissues. Lately, next-generation sequencing has allowed the discovery of new small-RNAs deriving from longer non-coding RNAs, including small-RNAs from rRNAs (srRNAs). Here, we systemically investigated srRNAs of maternal- or somatic-type 18S, 5.8S, 28S, with small-RNAseq from many zebrafish developmental stages. We identified new srRNAs for each rRNA. For 5.8S, we found srRNA consisting of the 5' or 3' halves, with only the latter having different sequence for the maternal- and somatic-types. For 18S, we discovered 21 nt srRNA from the 5' end of the 18S rRNA with a striking resemblance to microRNAs; as it is likely processed from a stem-loop precursor and present in human and mouse Argonaute-complexed small-RNA. For 28S, an abundant 80 nt srRNA from the 3' end of the 28S rRNA was found. The expression levels during embryogenesis of these srRNA indicate they are not generated from rRNA degradation and might have a role in the zebrafish development.

Pulmonary tuberculosis

Science.gov (United States)

TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

DeepBase: annotation and discovery of microRNAs and other noncoding RNAs from deep-sequencing data.

Science.gov (United States)

Yang, Jian-Hua; Qu, Liang-Hu

2012-01-01

Recent advances in high-throughput deep-sequencing technology have produced large numbers of short and long RNA sequences and enabled the detection and profiling of known and novel microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) at unprecedented sensitivity and depth. In this chapter, we describe the use of deepBase, a database that we have developed to integrate all public deep-sequencing data and to facilitate the comprehensive annotation and discovery of miRNAs and other ncRNAs from these data. deepBase provides an integrative, interactive, and versatile web graphical interface to evaluate miRBase-annotated miRNA genes and other known ncRNAs, explores the expression patterns of miRNAs and other ncRNAs, and discovers novel miRNAs and other ncRNAs from deep-sequencing data. deepBase also provides a deepView genome browser to comparatively analyze these data at multiple levels. deepBase is available at http://deepbase.sysu.edu.cn/.

A comparative study of sequence- and structure-based features of small RNAs and other RNAs of bacteria.

Science.gov (United States)

Barik, Amita; Das, Santasabuj

2018-01-02

Small RNAs (sRNAs) in bacteria have emerged as key players in transcriptional and post-transcriptional regulation of gene expression. Here, we present a statistical analysis of different sequence- and structure-related features of bacterial sRNAs to identify the descriptors that could discriminate sRNAs from other bacterial RNAs. We investigated a comprehensive and heterogeneous collection of 816 sRNAs, identified by northern blotting across 33 bacterial species and compared their various features with other classes of bacterial RNAs, such as tRNAs, rRNAs and mRNAs. We observed that sRNAs differed significantly from the rest with respect to G+C composition, normalized minimum free energy of folding, motif frequency and several RNA-folding parameters like base-pairing propensity, Shannon entropy and base-pair distance. Based on the selected features, we developed a predictive model using Random Forests (RF) method to classify the above four classes of RNAs. Our model displayed an overall predictive accuracy of 89.5%. These findings would help to differentiate bacterial sRNAs from other RNAs and further promote prediction of novel sRNAs in different bacterial species.

Learn About Tuberculosis

Science.gov (United States)

... Diseases > Lung Disease Lookup > Tuberculosis (TB) Learn About Tuberculosis Tuberculosis (TB) is an airborne bacterial infection caused by the organism Mycobacterium tuberculosis that primarily affects the lungs, although other organs ...

TUBERCULOSIS

Directory of Open Access Journals (Sweden)

Tarik Bajrović

2013-10-01

Full Text Available Tuberculosis, known as the "White Plague" in the early 19th century, is the infectious disease, which is being researched today even in some of the most developed countries in the world. Epidemiological- epizootiological research points to the importance of pasteurizing milk as well as the transmission in aerosolized droplets in humans and animals. Mycobacterium tuberculosis (Mtb, M. bovis, M. africanum and M. microti are the mycobacteria that cause tuberculosis. Other mycobacteria cause diseases commonly known as mycobacteriosae. Pathogenesis of tuberculosis includes both host- related and mycobacterium-related factors (virulence. Mtb acts through the expression of various genes and their proteins that are detectable in the serums of the diseased only, proving these proteins are formed in the course of the disease. In humans, a diagnosis is established by the detection of antigens (and antibodies, and in animals, with the allergy tests. As far as the bovine tuberculosis is concerned, the combination of skin tuberculin and blood gamma interferon test is recommended. Sequential genome (Mtb analysis has given the basis for further research of the new vaccines.Key words: Tuberculosis, pathogenesis, immunity

Plant and Animal microRNAs (miRNAs) and Their Potential for Inter-kingdom Communication.

Science.gov (United States)

Zhao, Yuhai; Cong, Lin; Lukiw, Walter J

2018-01-01

microRNAs (miRNAs) comprise a class of ~18-25 nucleotide (nt) single-stranded non-coding RNAs (sncRNAs) that are the smallest known carriers of gene-encoded, post-transcriptional regulatory information in both plants and animals. There are many fundamental similarities between plant and animal miRNAs-the miRNAs of both kingdoms play essential roles in development, aging and disease, and the shaping of the transcriptome of many cell types. Both plant and animal miRNAs appear to predominantly exert their genetic and transcriptomic influences by regulating gene expression at the level of messenger RNA (mRNA) stability and/or translational inhibition. Certain miRNA species, such as miRNA-155, miRNA-168, and members of the miRNA-854 family may be expressed in both plants and animals, suggesting a common origin and functional selection of specific miRNAs over vast periods of evolution (for example, Arabidopsis thaliana-Homo sapiens divergence ~1.5 billion years). Although there is emerging evidence for cross-kingdom miRNA communication-that plant-enriched miRNAs may enter the diet and play physiological and/or pathophysiological roles in human health and disease-some research reports repudiate this possibility. This research paper highlights some recent, controversial, and remarkable findings in plant- and animal-based miRNA signaling research with emphasis on the intriguing possibility that dietary miRNAs and/or sncRNAs may have potential to contribute to both intra- and inter-kingdom signaling, and in doing so modulate molecular-genetic mechanisms associated with human health and disease.

Controlling the Seedbeds of Tuberculosis: Diagnosis and Treatment of Tuberculosis Infection

Science.gov (United States)

Rangaka, Molebogeng X.; Cavalcante, Solange C.; Marais, Ben J.; Thim, Sok; Martinson, Neil A.; Swaminathan, Soumya; Chaisson, Richard E.

2015-01-01

The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a critical opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programs focusing on single strategies rather than comprehensive programs that deliver an integrated arsenal for tuberculosis control may continue to struggle. Tuberculosis preventive therapy is a poorly utilized tool that is essential for controlling the reservoirs of disease that drive the current epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. This paper outlines challenges to implementation of preventive therapy and provides pragmatic suggestions for overcoming them. It further advocates for tuberculosis preventive therapy as the core of a renewed global focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics, and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems, community engagement, and enhance sustainable large scale implementation of preventive therapy programs. PMID:26515679

Tuberculosis (TB)

Science.gov (United States)

... with facebook share with twitter share with linkedin Tuberculosis Go to Information for Researchers ► Credit: NIAID Scanning ... are drug resistant. Why Is the Study of Tuberculosis a Priority for NIAID? Tuberculosis is one of ...

Tuberculosis and nutrition

Directory of Open Access Journals (Sweden)

Gupta Krishna

2009-01-01

Full Text Available Malnutrition and tuberculosis are both problems of considerable magnitude in most of the underdeveloped regions of the world. These two problems tend to interact with each other. Tuberculosis mortality rates in different economic groups in a community tend to vary inversely with their economic levels. Similarly, nutritional status is significantly lower in patients with active tuberculosis compared with healthy controls. Malnutrition can lead to secondary immunodeficiency that increases the host′s susceptibility to infection. In patients with tuberculosis, it leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting. Both, protein-energy malnutrition and micronutrients deficiencies increase the risk of tuberculosis. It has been found that malnourished tuberculosis patients have delayed recovery and higher mortality rates than well-nourished patients. Nutritional status of patients improves during tuberculosis chemotherapy. High prevalence of human immunodeficiency (HIV infection in the underdeveloped countries further aggravates the problem of malnutrition and tuberculosis. Effect of malnutrition on childhood tuberculosis and tuberculin skin test are other important considerations. Nutritional supplementation may represent a novel approach for fast recovery in tuberculosis patients. In addition, raising nutritional status of population may prove to be an effective measure to control tuberculosis in underdeveloped areas of world.

microRNAs in hematopoiesis

NARCIS (Netherlands)

Lazare, Seka S.; Wojtowicz, Edyta E.; Bystrykh, Leonid V.; de Haan, Gerald

2014-01-01

miRNAs have been implicated in all stages of hematopoiesis including maintenance of self-renewal of hematopoietic stem cells (HSCs) and differentiation into mature blood cells. Regulation by miRNAs is markedly intertwined with transcription factors. In this review, we highlight miRNAs shown to be

miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments

Directory of Open Access Journals (Sweden)

Huwer Hanno

2009-10-01

Full Text Available Abstract Background Deregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients. Due to their inherent stability miRNAs may offer themselves for blood based tumor diagnosis. Here we addressed the question whether there is a sufficient number of miRNAs deregulated in blood cells of cancer patients to be able to distinguish between cancer patients and controls. Methods We synthesized 866 human miRNAs and miRNA star sequences as annotated in the Sanger miRBase onto a microarray designed by febit biomed gmbh. Using the fully automated Geniom Real Time Analyzer platform, we analyzed the miRNA expression in 17 blood cell samples of patients with non-small cell lung carcinomas (NSCLC and in 19 blood samples of healthy controls. Results Using t-test, we detected 27 miRNAs significantly deregulated in blood cells of lung cancer patients as compared to the controls. Some of these miRNAs were validated using qRT-PCR. To estimate the value of each deregulated miRNA, we grouped all miRNAs according to their diagnostic information that was measured by Mutual Information. Using a subset of 24 miRNAs, a radial basis function Support Vector Machine allowed for discriminating between blood cellsamples of tumor patients and controls with an accuracy of 95.4% [94.9%-95.9%], a specificity of 98.1% [97.3%-98.8%], and a sensitivity of 92.5% [91.8%-92.5%]. Conclusion Our findings support the idea that neoplasia may lead to a deregulation of miRNA expression in blood cells of cancer patients compared to blood cells of healthy individuals. Furthermore, we provide evidence that miRNA patterns can be used to detect human cancers from blood cells.

EVLncRNAs: a manually curated database for long non-coding RNAs validated by low-throughput experiments

Science.gov (United States)

Zhao, Huiying; Yu, Jiafeng; Guo, Chengang; Dou, Xianghua; Song, Feng; Hu, Guodong; Cao, Zanxia; Qu, Yuanxu

2018-01-01

Abstract Long non-coding RNAs (lncRNAs) play important functional roles in various biological processes. Early databases were utilized to deposit all lncRNA candidates produced by high-throughput experimental and/or computational techniques to facilitate classification, assessment and validation. As more lncRNAs are validated by low-throughput experiments, several databases were established for experimentally validated lncRNAs. However, these databases are small in scale (with a few hundreds of lncRNAs only) and specific in their focuses (plants, diseases or interactions). Thus, it is highly desirable to have a comprehensive dataset for experimentally validated lncRNAs as a central repository for all of their structures, functions and phenotypes. Here, we established EVLncRNAs by curating lncRNAs validated by low-throughput experiments (up to 1 May 2016) and integrating specific databases (lncRNAdb, LncRANDisease, Lnc2Cancer and PLNIncRBase) with additional functional and disease-specific information not covered previously. The current version of EVLncRNAs contains 1543 lncRNAs from 77 species that is 2.9 times larger than the current largest database for experimentally validated lncRNAs. Seventy-four percent lncRNA entries are partially or completely new, comparing to all existing experimentally validated databases. The established database allows users to browse, search and download as well as to submit experimentally validated lncRNAs. The database is available at http://biophy.dzu.edu.cn/EVLncRNAs. PMID:28985416

TUBERCULOSIS

OpenAIRE

Tarik Bajrović; Mahmud Nurkić; Šukrija Zvizdić

2013-01-01

Tuberculosis, known as the "White Plague" in the early 19th century, is the infectious disease, which is being researched today even in some of the most developed countries in the world. Epidemiological- epizootiological research points to the importance of pasteurizing milk as well as the transmission in aerosolized droplets in humans and animals. Mycobacterium tuberculosis (Mtb), M. bovis, M. africanum and M. microti are the mycobacteria that cause tuberculosis. Other mycobacteria cause dis...

Tuberculosis

OpenAIRE

C. Robert Horsburgh, Jr

2014-01-01

This article reviews the published literature on tuberculosis from September 2012 to August 2013 and describes important advances in tuberculosis epidemiology, microbiology, pathology, clinical pharmacology, genetics, treatment and prevention.

Intronic microRNAs

International Nuclear Information System (INIS)

Ying, S.-Y.; Lin, S.-L.

2005-01-01

MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular mRNAs that contain partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. MiRNA was originally discovered in the intergenic regions of the Caenorhabditis elegans genome as native RNA fragments that modulate a wide range of genetic regulatory pathways during animal development. However, neither RNA promoter nor polymerase responsible for miRNA biogenesis was determined. Recent findings of intron-derived miRNA in C. elegans, mouse, and human have inevitably led to an alternative pathway for miRNA biogenesis, which relies on the coupled interaction of Pol-II-mediated pre-mRNA transcription and intron excision, occurring in certain nuclear regions proximal to genomic perichromatin fibrils

Bovine tuberculosis

Science.gov (United States)

Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti) . Mycobacterium bovis is the species most often isolated from tuberculous cat...

MicroRNAs and Periodontal Homeostasis.

Science.gov (United States)

Luan, X; Zhou, X; Trombetta-eSilva, J; Francis, M; Gaharwar, A K; Atsawasuwan, P; Diekwisch, T G H

2017-05-01

MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels. In the periodontium, miRNAs play key roles in development and periodontal homeostasis and during the loss of periodontal tissue integrity as a result of periodontal disease. As part of the anabolic phase of periodontal homeostasis and periodontal development, miRNAs direct periodontal fibroblasts toward alveolar bone lineage differentiation and new bone formation through WNT, bone morphogenetic protein, and Notch signaling pathways. miRNAs contribute equally to the catabolic aspect of periodontal homeostasis as they affect osteoclastogenesis and osteoclast function, either by directly promoting osteoclast activity or by inhibiting osteoclast signaling intermediaries or through negative feedback loops. Their small size and ability to target multiple regulatory networks of related sets of genes have predisposed miRNAs to become ideal candidates for drug delivery and tissue regeneration. To address the immense therapeutic potential of miRNAs and their antagomirs, an ever growing number of delivery approaches toward clinical applications have been developed, including nanoparticle carriers and secondary structure interference inhibitor systems. However, only a fraction of the miRNAs involved in periodontal health and disease are known today. It is anticipated that continued research will lead to a more comprehensive understanding of the periodontal miRNA world, and a systematic

Targeting of microRNAs for therapeutics

DEFF Research Database (Denmark)

Stenvang, Jan; Lindow, Morten; Kauppinen, Sakari

2008-01-01

miRNAs (microRNAs) comprise a class of small endogenous non-coding RNAs that post-transcriptionally repress gene expression by base-pairing with their target mRNAs. Recent evidence has shown that miRNAs play important roles in a wide variety of human diseases, such as viral infections, cancer...

Congenital tuberculosis

African Journals Online (AJOL)

Prof Ezechukwu

2012-06-20

Jun 20, 2012 ... Key words: Congenital tuberculo- sis, case report, miliary tuberculosis. Introduction. Congenital tuberculosis defines tuberculosis in infants of .... tary TB and otitis media, resulting in seizures, deafness, and death. It is therefore not surprising that the index case who presented at twelve weeks of age, had ...

Tuberculosis verrucosa cutis

Directory of Open Access Journals (Sweden)

Krishnabharath S

2017-08-01

Full Text Available We report a case of 23-year-old male patient with tuberculosis verrucous cutis on the foot for a duration of six months without responding to routine treatment. Tuberculosis is a common disease worldwide. Extrapulmonary tuberculosis contributes to 10% of cases. Cutaneous tuberculosis occupies a small spectrum of extrapulmonary tuberculosis. Tuberculosis verrucosa cutis is an exogenous infection occurring in a previously sensitized patient by direct inoculation of the organism. It occurs in sensitized patients with a moderate to high immune response. The diagnosis in our patient was confirmed by history, clinical examination, histopathological examination and the patient’s response to anti-tuberculous therapy.

Modeling post-transcriptional regulation activity of small non-coding RNAs in Escherichia coli.

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Wang, Rui-Sheng; Jin, Guangxu; Zhang, Xiang-Sun; Chen, Luonan

2009-04-29

Transcriptional regulation is a fundamental process in biological systems, where transcription factors (TFs) have been revealed to play crucial roles. In recent years, in addition to TFs, an increasing number of non-coding RNAs (ncRNAs) have been shown to mediate post-transcriptional processes and regulate many critical pathways in both prokaryotes and eukaryotes. On the other hand, with more and more high-throughput biological data becoming available, it is possible and imperative to quantitatively study gene regulation in a systematic and detailed manner. Most existing studies for inferring transcriptional regulatory interactions and the activity of TFs ignore the possible post-transcriptional effects of ncRNAs. In this work, we propose a novel framework to infer the activity of regulators including both TFs and ncRNAs by exploring the expression profiles of target genes and (post)transcriptional regulatory relationships. We model the integrated regulatory system by a set of biochemical reactions which lead to a log-bilinear problem. The inference process is achieved by an iterative algorithm, in which two linear programming models are efficiently solved. In contrast to available related studies, the effects of ncRNAs on transcription process are considered in this work, and thus more reasonable and accurate reconstruction can be expected. In addition, the approach is suitable for large-scale problems from the viewpoint of computation. Experiments on two synthesized data sets and a model system of Escherichia coli (E. coli) carbon source transition from glucose to acetate illustrate the effectiveness of our model and algorithm. Our results show that incorporating the post-transcriptional regulation of ncRNAs into system model can mine the hidden effects from the regulation activity of TFs in transcription processes and thus can uncover the biological mechanisms in gene regulation in a more accurate manner. The software for the algorithm in this paper is available

The tuberculosis hospital in Hohenkrug, Stettin. Department of Genitourinary Tuberculosis.

Science.gov (United States)

Zajaczkowski, Tadeusz

2012-01-01

Towards the end of the 19th century, Europe turned particular attention to the problem of tuberculosis, at that time the most serious social disease. In the majority of cases, pulmonary tuberculosis had a fatal outcome owing to the lack of effective drugs and methods of treatment. Due to poor sanitary conditions, particularly as regards dwellings, pulmonary tuberculosis was able to spread rapidly. Hospital departments were reluctant to admit patients suffering from tuberculosis. It was only after the discoveries of Robert Koch (bacillus tubercle in 1882) that the cause of the disease became understood and methods of treatment began to be developed. A modern sanatorium and hospital with 270 beds was erected in Hohenkrug (today Szczecin-Zdunowo) between 1915 and 1930. Patients could now be treated with modern methods, surgically in most cases. After the Second World War, pulmonary tuberculosis was still an enormous epidemiologic problem. In 1949, the Polish authorities opened a 400-bed sanatoriumin Zdunowo. The methods of treatment were not much different from pre-war practice and it was only the routine introduction of antituberculotic drugs during the fifties of the past century that brought about a radical change in the fight against tuberculosis. The growing numbers of patients with tuberculosis of the genitourinary system led to the opening in 1958 of a 40-bed specialist ward at the Tuberculosis Sanatorium in Zdunowo. It should be emphasized that the Department of Genitourinary Tuberculosis in Szczecin-Zdunowo was a historical necessity and a salvation for thousands of patients from Northern Poland. The Department totally fulfilled its social duties thanks to the commitment of many outstanding persons dedicated to helping the patients. This unit was finally closed in 1987 because the demand for surgical treatment of tuberculosis was declining concurrently with the advent of new and potent antituberculotics and falling number of new cases of genitourinary

Radiographic differentiation of atypical tuberculosis from mycobacterium tuberculosis

International Nuclear Information System (INIS)

Tarver, R.D.; Pearcy, E.A.; Conces, D.J. Jr.; Mathur, P.N.

1987-01-01

The chest radiographs of 95 patients with the new diagnosis of atypical turberculosis were reviewed to determine if any significant differences between atypical tuberculosis and that caused by Mycobacterium tuberculosis could be discerned. Findings included upper lobe involvement in B4 of the 95 patients and cavities in 76, with nearly equal groups having no, moderate, or extensive surrounding alveolar disease. Nodules were common; in six patients a nodule was the sole manifestation of disease. Adenopathy was seen in 12 of the 95 patients, atlectasis in 45, pleural thickening in 90, and effusions in three. These radiographic findings did not allow the radiographic differentiation of atypical tuberculosis from Mycobacterium tuberculosis infection

MicroRNAs regulate osteogenesis and chondrogenesis

International Nuclear Information System (INIS)

Dong, Shiwu; Yang, Bo; Guo, Hongfeng; Kang, Fei

2012-01-01

Highlights: ► To focus on the role of miRNAs in chondrogenesis and osteogenesis. ► Involved in the regulation of miRNAs in osteoarthritis. ► To speculate some therapeutic targets for bone diseases. -- Abstract: MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation.

MicroRNAs regulate osteogenesis and chondrogenesis

Energy Technology Data Exchange (ETDEWEB)

Dong, Shiwu, E-mail: shiwudong@gmail.com [Laboratory of Biomechanics, Department of Anatomy, The Third Military Medical University, Chongqing (China); Yang, Bo; Guo, Hongfeng; Kang, Fei [Laboratory of Biomechanics, Department of Anatomy, The Third Military Medical University, Chongqing (China)

2012-02-24

Highlights: Black-Right-Pointing-Pointer To focus on the role of miRNAs in chondrogenesis and osteogenesis. Black-Right-Pointing-Pointer Involved in the regulation of miRNAs in osteoarthritis. Black-Right-Pointing-Pointer To speculate some therapeutic targets for bone diseases. -- Abstract: MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation.

Time-Dependent Expression Profiles of microRNAs and mRNAs in Rat Milk Whey

Science.gov (United States)

Izumi, Hirohisa; Kosaka, Nobuyoshi; Shimizu, Takashi; Sekine, Kazunori; Ochiya, Takahiro; Takase, Mitsunori

2014-01-01

Functional RNAs, such as microRNA (miRNA) and mRNA, are present in milk, but their roles are unknown. To clarify the roles of milk RNAs, further studies using experimental animals such as rats are needed. However, it is unclear whether rat milk also contains functional RNAs and what their time dependent expression profiles are. Thus, we prepared total RNA from whey isolated from rat milk collected on days 2, 9, and 16 postpartum and analyzed using microarrays and quantitative PCR. The concentration of RNA in colostrum whey (day 2) was markedly higher than that in mature milk whey (days 9 and 16). Microarray analysis detected 161 miRNAs and 10,948 mRNA transcripts. Most of the miRNAs and mRNA transcripts were common to all tested milks. Finally, we selected some immune- and development-related miRNAs and mRNAs, and analysed them by quantitative PCR (in equal sample volumes) to determine their time-dependent changes in expression in detail. Some were significantly more highly expressed in colostrum whey than in mature milk whey, but some were expressed equally. And mRNA expression levels of some cytokines and hormones did not reflect the protein levels. It is still unknown whether RNAs in milk play biological roles in neonates. However, our data will help guide future in vivo studies using experimental animals such as rats. PMID:24533154

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

NARCIS (Netherlands)

Miesen, P.; Ivens, A.; Buck, A.H.; Rij, R.P. van

2016-01-01

In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of

Interplay of noncoding RNAs, mRNAs, and proteins during the growth of eukaryotic cells

International Nuclear Information System (INIS)

Zhdanov, V. P.

2010-01-01

Numerous biological functions of noncoding RNAs (ncRNAs) in eukaryotic cells are based primarily on their ability to pair with target mRNAs and then either to prevent translation or to result in rapid degradation of the mRNA-ncRNA complex. Using a general model describing this scenario, we show that ncRNAs may help to maintain constant mRNA and protein concentrations during the growth of cells. The possibility of observation of this effect on the global scale is briefly discussed.

Bis-spirochromanones as potent inhibitors of Mycobacterium tuberculosis: synthesis and biological evaluation.

Science.gov (United States)

Dongamanti, Ashok; Aamate, Vikas Kumar; Devulapally, Mohan Gandhi; Gundu, Srinivas; Balabadra, Saikrishna; Manga, Vijjulatha; Yogeeswari, Perumal; Sriram, Dharmarajan; Balasubramanian, Sridhar

2017-11-01

On the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from 2-hydroxyacetophenone and 1,4-dioxaspiro[4.5] decan-8-one using a Kabbe condensation approach. The synthesized bis-spirochromanones were established based on their spectral data and X-ray crystal structure of 6e. All synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain, finding that some products exhibited good antimycobacterial activity with minimum inhibitory concentration as low as [Formula: see text]. Docking studies were carried out to identify the binding interactions of compounds II, 6a and 6n with FtsZ. Compounds exhibiting good in vitro potency in the MTB MIC assay were further evaluated for toxicity using the HEK cell line.

Annotation of mammalian primary microRNAs

Directory of Open Access Journals (Sweden)

Enright Anton J

2008-11-01

Full Text Available Abstract Background MicroRNAs (miRNAs are important regulators of gene expression and have been implicated in development, differentiation and pathogenesis. Hundreds of miRNAs have been discovered in mammalian genomes. Approximately 50% of mammalian miRNAs are expressed from introns of protein-coding genes; the primary transcript (pri-miRNA is therefore assumed to be the host transcript. However, very little is known about the structure of pri-miRNAs expressed from intergenic regions. Here we annotate transcript boundaries of miRNAs in human, mouse and rat genomes using various transcription features. The 5' end of the pri-miRNA is predicted from transcription start sites, CpG islands and 5' CAGE tags mapped in the upstream flanking region surrounding the precursor miRNA (pre-miRNA. The 3' end of the pri-miRNA is predicted based on the mapping of polyA signals, and supported by cDNA/EST and ditags data. The predicted pri-miRNAs are also analyzed for promoter and insulator-associated regulatory regions. Results We define sets of conserved and non-conserved human, mouse and rat pre-miRNAs using bidirectional BLAST and synteny analysis. Transcription features in their flanking regions are used to demarcate the 5' and 3' boundaries of the pri-miRNAs. The lengths and boundaries of primary transcripts are highly conserved between orthologous miRNAs. A significant fraction of pri-miRNAs have lengths between 1 and 10 kb, with very few introns. We annotate a total of 59 pri-miRNA structures, which include 82 pre-miRNAs. 36 pri-miRNAs are conserved in all 3 species. In total, 18 of the confidently annotated transcripts express more than one pre-miRNA. The upstream regions of 54% of the predicted pri-miRNAs are found to be associated with promoter and insulator regulatory sequences. Conclusion Little is known about the primary transcripts of intergenic miRNAs. Using comparative data, we are able to identify the boundaries of a significant proportion of

Genomic Organization of Zebrafish microRNAs

Directory of Open Access Journals (Sweden)

Paydar Ima

2008-05-01

Full Text Available Abstract Background microRNAs (miRNAs are small (~22 nt non-coding RNAs that regulate cell movement, specification, and development. Expression of miRNAs is highly regulated, both spatially and temporally. Based on direct cloning, sequence conservation, and predicted secondary structures, a large number of miRNAs have been identified in higher eukaryotic genomes but whether these RNAs are simply a subset of a much larger number of noncoding RNA families is unknown. This is especially true in zebrafish where genome sequencing and annotation is not yet complete. Results We analyzed the zebrafish genome to identify the number and location of proven and predicted miRNAs resulting in the identification of 35 new miRNAs. We then grouped all 415 zebrafish miRNAs into families based on seed sequence identity as a means to identify possible functional redundancy. Based on genomic location and expression analysis, we also identified those miRNAs that are likely to be encoded as part of polycistronic transcripts. Lastly, as a resource, we compiled existing zebrafish miRNA expression data and, where possible, listed all experimentally proven mRNA targets. Conclusion Current analysis indicates the zebrafish genome encodes 415 miRNAs which can be grouped into 44 families. The largest of these families (the miR-430 family contains 72 members largely clustered in two main locations along chromosome 4. Thus far, most zebrafish miRNAs exhibit tissue specific patterns of expression.

MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis.

Science.gov (United States)

Rothchild, Alissa C; Sissons, James R; Shafiani, Shahin; Plaisier, Christopher; Min, Deborah; Mai, Dat; Gilchrist, Mark; Peschon, Jacques; Larson, Ryan P; Bergthaler, Andreas; Baliga, Nitin S; Urdahl, Kevin B; Aderem, Alan

2016-10-11

The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.

Tuberculosis en el niño Tuberculosis in the child

OpenAIRE

J. Ruiz Contreras

2011-01-01

La tuberculosis infantil representa alrededor del 5% de todos los casos de tuberculosis en los países desarrollados, pero el porcentaje es mucho mayor en los países en vías de desarrollo. En España, los niños menores de 14 años representan el 5,6% de todos los casos de tuberculosis. Aproximadamente, dos tercios de los casos de tuberculosis en niños europeos de 0 a 14 años ocurren en Europa del Este. En estos países, la incidencia más alta de tuberculosis ocurre en adultos jóvenes, entre los 2...

Small silencing RNAs: an expanding universe.

Science.gov (United States)

Ghildiyal, Megha; Zamore, Phillip D

2009-02-01

Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, their modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected, and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats.

MicroRNAs in the Hypothalamus

DEFF Research Database (Denmark)

Meister, Björn; Herzer, Silke; Silahtaroglu, Asli

2013-01-01

MicroRNAs (miRNAs) are short (∼22 nucleotides) non-coding ribonucleic acid (RNA) molecules that negatively regulate the expression of protein-coding genes. Posttranscriptional silencing of target genes by miRNA is initiated by binding to the 3'-untranslated regions of target mRNAs, resulting...... of the hypothalamus and miRNAs have recently been shown to be important regulators of hypothalamic control functions. The aim of this review is to summarize some of the current knowledge regarding the expression and role of miRNAs in the hypothalamus.......RNA molecules are abundantly expressed in tissue-specific and regional patterns and have been suggested as potential biomarkers, disease modulators and drug targets. The central nervous system is a prominent site of miRNA expression. Within the brain, several miRNAs are expressed and/or enriched in the region...

Preparation and biological evaluation of ethionamide-mesoporous silicon nanoparticles against Mycobacterium tuberculosis

OpenAIRE

Vale, Nuno; Correia, Alexandra; Silva, Sara; Figueiredo, Patrícia; Mäkilä, , Ermei; Salonen, Jarno; Hirvonen, Jouni; Pedrosa, Jorge; Santos Hélder A.; Fraga, Alexandra

2017-01-01

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous si...

Retrotransposons and non-protein coding RNAs

DEFF Research Database (Denmark)

Mourier, Tobias; Willerslev, Eske

2009-01-01

does not merely represent spurious transcription. We review examples of functional RNAs transcribed from retrotransposons, and address the collection of non-protein coding RNAs derived from transposable element sequences, including numerous human microRNAs and the neuronal BC RNAs. Finally, we review...

Synthesis of new radiotracers for tuberculosis diagnosis

International Nuclear Information System (INIS)

Keskes, Badis

2009-01-01

Tuberculosis remains a worldwide health problem and its diagnosis presents a major challenge. The examinations currently employed are little appreciable and so far there is no reliable diagnosis test. These last years, the development of the new radiopharmaceuticals, referred to diagnosis, has revived interest in the search for new molecules with a tropism to a particular disease. Thanks to this field, which lies at the interface of organic and organometallic chemistry, nuclear medicine and biology, we have been led to synthesize a technetium radiotracer linked to isoniazid. For the identification of this radiotracer, we used its similar rhenium model. (Author)

Tuberculosis treatment among smear positive tuberculosis patients

International Nuclear Information System (INIS)

Munir, M.K.; Iqbal, R.; Shabbir, I.; Chaudhry, K

2012-01-01

Tuberculosis is a major health problem in many parts of the world. Delay in initiation of the treatment may result in prolonged infectious state, drug resistance, relapse and death. Objectives: To determine the factors responsible for not starting tuberculosis treatment among smear positive tuberculosis patients. Study type, settings and duration: This cross sectional study was done at Pakistan Medical Research Council TB Research Center, King Edward Medical University, Lahore, from fifth March 2010 to fifth December 2010. Patients and Methods: Fifty sputum smear positive patients of tuberculosis who did not register themselves in treatment register and presumably did not initiate anti tuberculosis treatment were contacted using telephone or traced by their home addresses. Once contact was established, they were inquired about the reasons for not starting tuberculosis treatment. Results: Of 50 patients 38(76%)belonged to the lower socio economic class and 12(24%) to the lower middle class. Fourteen patients (28%) were illiterate and 23(46%) had only 8 years of education. Of the 50 cases 41(82%) were taking treatment from traditional healers and 4% did not go back to the DOTS program. Physical condition of the patient, social, domestic and religious issues also played some role in default. Conclusions: Lack of health education and poverty were the main factors responsible for non compliance from treatment. Policy message: Sputum testing sites should have a paramedic who should educate the patients about the benefits of treatment and the dangers of default or partial treatment. (author)

Deep sequencing of Brachypodium small RNAs at the global genome level identifies microRNAs involved in cold stress response

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Chong Kang

2009-09-01

Full Text Available Abstract Background MicroRNAs (miRNAs are endogenous small RNAs having large-scale regulatory effects on plant development and stress responses. Extensive studies of miRNAs have only been performed in a few model plants. Although miRNAs are proved to be involved in plant cold stress responses, little is known for winter-habit monocots. Brachypodium distachyon, with close evolutionary relationship to cool-season cereals, has recently emerged as a novel model plant. There are few reports of Brachypodium miRNAs. Results High-throughput sequencing and whole-genome-wide data mining led to the identification of 27 conserved miRNAs, as well as 129 predicted miRNAs in Brachypodium. For multiple-member conserved miRNA families, their sizes in Brachypodium were much smaller than those in rice and Populus. The genome organization of miR395 family in Brachypodium was quite different from that in rice. The expression of 3 conserved miRNAs and 25 predicted miRNAs showed significant changes in response to cold stress. Among these miRNAs, some were cold-induced and some were cold-suppressed, but all the conserved miRNAs were up-regulated under cold stress condition. Conclusion Our results suggest that Brachypodium miRNAs are composed of a set of conserved miRNAs and a large proportion of non-conserved miRNAs with low expression levels. Both kinds of miRNAs were involved in cold stress response, but all the conserved miRNAs were up-regulated, implying an important role for cold-induced miRNAs. The different size and genome organization of miRNA families in Brachypodium and rice suggest that the frequency of duplication events or the selection pressure on duplicated miRNAs are different between these two closely related plant species.

Novel meiotic miRNAs and indications for a role of phasiRNAs in meiosis

Science.gov (United States)

Small RNAs (sRNA) add additional layers to the regulation of gene expression, with siRNAs directing gene silencing at the DNA level by RdDM (RNA-directed DNA methylation), and miRNAs directing post-transcriptional regulation of specific target genes, mostly by mRNA cleavage. We used manually isolate...

Non-Protein Coding RNAs

CERN Document Server

Walter, Nils G; Batey, Robert T

2009-01-01

This book assembles chapters from experts in the Biophysics of RNA to provide a broadly accessible snapshot of the current status of this rapidly expanding field. The 2006 Nobel Prize in Physiology or Medicine was awarded to the discoverers of RNA interference, highlighting just one example of a large number of non-protein coding RNAs. Because non-protein coding RNAs outnumber protein coding genes in mammals and other higher eukaryotes, it is now thought that the complexity of organisms is correlated with the fraction of their genome that encodes non-protein coding RNAs. Essential biological processes as diverse as cell differentiation, suppression of infecting viruses and parasitic transposons, higher-level organization of eukaryotic chromosomes, and gene expression itself are found to largely be directed by non-protein coding RNAs. The biophysical study of these RNAs employs X-ray crystallography, NMR, ensemble and single molecule fluorescence spectroscopy, optical tweezers, cryo-electron microscopy, and ot...

Multidrug-resistant tuberculosis

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McNerney Ruth

2008-01-01

Full Text Available Abstract Background With almost 9 million new cases each year, tuberculosis remains one of the most feared diseases on the planet. Led by the STOP-TB Partnership and WHO, recent efforts to combat the disease have made considerable progress in a number of countries. However, the emergence of mutated strains of Mycobacterium tuberculosis that are resistant to the major anti-tuberculosis drugs poses a deadly threat to control efforts. Multidrug-resistant tuberculosis (MDR-TB has been reported in all regions of the world. More recently, extensively drug resistant-tuberculosis (XDR-TB that is also resistant to second line drugs has emerged in a number of countries. To ensure that adequate resources are allocated to prevent the emergence and spread of drug resistance it is important to understand the scale of the problem. In this article we propose that current methods of describing the epidemiology of drug resistant tuberculosis are not adequate for this purpose and argue for the inclusion of population based statistics in global surveillance data. Discussion Whereas the prevalence of tuberculosis is presented as the proportion of individuals within a defined population having disease, the prevalence of drug resistant tuberculosis is usually presented as the proportion of tuberculosis cases exhibiting resistance to anti-tuberculosis drugs. Global surveillance activities have identified countries in Eastern Europe, the former Soviet Union and regions of China as having a high proportion of MDR-TB cases and international commentary has focused primarily on the urgent need to improve control in these settings. Other regions, such as sub-Saharan Africa have been observed as having a low proportion of drug resistant cases. However, if one considers the incidence of new tuberculosis cases with drug resistant disease in terms of the population then countries of sub-Saharan Africa have amongst the highest rates of transmitted MDR-TB in the world. We propose

Tuberculosis como enfermedad ocupacional Tuberculosis as occupational disease

OpenAIRE

Alberto Mendoza-Ticona

2012-01-01

Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis ...

Modulation of microRNA activity by semi-microRNAs (smiRNAs

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Isabelle ePlante

2012-06-01

Full Text Available The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing the formation of 19 to 24-nucleotide (nt long microRNAs. Subsequently incorporated into Ago2 effector complexes, microRNAs are known to regulate messenger RNA (mRNA translation. Whether shorter RNA species derived from microRNAs exist and play a role in mRNA regulation remains unknown. Here, we report the serendipitous discovery of a 12-nt long RNA species corresponding to the 5’ region of the microRNA let-7, and tentatively termed semi-microRNA, or smiRNA. Using a smiRNA derived from the precursor of miR-223 as a model, we show that 12-nt long smiRNA species are devoid of any direct mRNA regulatory activity, as assessed in a reporter gene activity assay in transfected cultured human cells. However, smiR-223 was found to modulate the ability of the microRNA from which it derives to mediate translational repression or cleavage of reporter mRNAs. Our findings suggest that smiRNAs may be generated along the microRNA pathway and participate to the control of gene expression by regulating the activity of the related full-length mature microRNA in vivo.

Identification of microRNAs actively involved in fatty acid biosynthesis in developing Brassica napus seeds using high-throughput sequencing

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Jia Wang

2016-10-01

Full Text Available Seed development has a critical role during the spermatophyte life cycle. In Brassica napus, a major oil crop, fatty acids are synthesized and stored in specific tissues during embryogenesis, and understanding the molecular mechanism underlying fatty acid biosynthesis during seed development is an important research goal. In this study, we constructed three small RNA libraries from early seeds at 14, 21 and 28 days after flowering (DAF and used high-throughput sequencing to examine microRNA (miRNA expression. A total of 85 known miRNAs from 30 families and 1,160 novel miRNAs were identified, of which 24, including 5 known and 19 novel miRNAs, were found to be involved in fatty acid biosynthesis. bna-miR156b, bna-miR156c, bna-miR156g, novel_mir_1706, novel_mir_1407, novel_mir_173, and novel_mir_104 were significantly down-regulated at 21 DAF and 28 DAF, whereas bna-miR159, novel_mir_1081, novel_mir_19 and novel_mir_555 were significantly up-regulated. In addition, we found that some miRNAs regulate functional genes that are directly involved in fatty acid biosynthesis and that other miRNAs regulate the process of fatty acid biosynthesis by acting on a large number of transcription factors. The miRNAs and their corresponding predicted targets were partially validated by quantitative RT-PCR. Our data suggest that diverse and complex miRNAs are involved in the seed development process and that miRNAs play important roles in fatty acid biosynthesis during seed development.

Levels of microRNA miR-16 and miR-155 are altered in serum of patients with tuberculosis and associate with responses to therapy.

Science.gov (United States)

Wagh, Vishal; Urhekar, Anant; Modi, Deepak

2017-01-01

Identification of blood biomarkers that can be useful for predicting Mycobacterium tuberculosis (M.TB) infection, effect of therapy and Multi Drug Resistant (MDR) TB infected individuals is clinically useful for combating tuberculosis epidemic. In this study, we have evaluated the levels of selected miRNAs in serum of TB and MDR TB patients. In addition, we have studied their levels in serum of patients post-therapy. The levels of 4-miRNAs (miR-16, miR-29a, miR-125b and miR-155) were measured in 30 newly diagnosed TB patients, 19 Multi Drug Resistant (MDR) TB patients, 10 patients who completed TB therapy and were TB negative. 30 healthy individuals were recruited as controls. The levels of the miRNAs were estimated by qRT-PCR. Of the four miRNAs studied, the levels of miR-16 were significantly elevated and miR-155 were significantly reduced in serum of TB patients as compared to uninfected controls. The Receiver Operating Characteristic (ROC) curve of miR-16 and miR-155 exhibited a significant distinguishing efficiency with an AUC value of 1 (95% CI, 1 to 1) and 0.967 (95% CI, 0.92-1.04) respectively. Following the therapy, the levels of miR-16 and miR-155 returned to those observed in healthy subjects. In patients with MDR TB, miR-155 was lower as compared to healthy controls and TB treated group but higher as compared to TB naïve patients. miR-16 levels were lowest in serum of MDR TB patients compared to TB naïve, TB treated group and healthy controls. In conclusion, miR-16 and miR-155 in serum may act as surrogate biomarker for studying TB infection, progression of therapy and MDR TB. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tuberculosis

NARCIS (Netherlands)

Ankrah, Alfred O; Glaudemans, Andor W J M; Maes, Alex; Van de Wiele, Christophe; Dierckx, Rudi A J O; Vorster, Mariza; Sathekge, Mike M

Tuberculosis (TB) is currently the world's leading cause of infectious mortality. Imaging plays an important role in the management of this disease. The complex immune response of the human body to Mycobacterium tuberculosis results in a wide array of clinical manifestations, making clinical and

Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA).

Science.gov (United States)

Li, Huinan; Wu, Cheng; Aramayo, Rodolfo; Sachs, Matthew S; Harlow, Mark L

2015-10-08

Synaptic vesicles (SVs) are neuronal presynaptic organelles that load and release neurotransmitter at chemical synapses. In addition to classic neurotransmitters, we have found that synaptic vesicles isolated from the electric organ of Torpedo californica, a model cholinergic synapse, contain small ribonucleic acids (sRNAs), primarily the 5' ends of transfer RNAs (tRNAs) termed tRNA fragments (trfRNAs). To test the evolutionary conservation of SV sRNAs we examined isolated SVs from the mouse central nervous system (CNS). We found abundant levels of sRNAs in mouse SVs, including trfRNAs and micro RNAs (miRNAs) known to be involved in transcriptional and translational regulation. This discovery suggests that, in addition to inducing changes in local dendritic excitability through the release of neurotransmitters, SVs may, through the release of specific trfRNAs and miRNAs, directly regulate local protein synthesis. We believe these findings have broad implications for the study of chemical synaptic transmission.

miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments

International Nuclear Information System (INIS)

Keller, Andreas; Leidinger, Petra; Borries, Anne; Wendschlag, Anke; Wucherpfennig, Frank; Scheffler, Matthias; Huwer, Hanno; Lenhof, Hans-Peter; Meese, Eckart

2009-01-01

Deregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients. Due to their inherent stability miRNAs may offer themselves for blood based tumor diagnosis. Here we addressed the question whether there is a sufficient number of miRNAs deregulated in blood cells of cancer patients to be able to distinguish between cancer patients and controls. We synthesized 866 human miRNAs and miRNA star sequences as annotated in the Sanger miRBase onto a microarray designed by febit biomed gmbh. Using the fully automated Geniom Real Time Analyzer platform, we analyzed the miRNA expression in 17 blood cell samples of patients with non-small cell lung carcinomas (NSCLC) and in 19 blood samples of healthy controls. Using t-test, we detected 27 miRNAs significantly deregulated in blood cells of lung cancer patients as compared to the controls. Some of these miRNAs were validated using qRT-PCR. To estimate the value of each deregulated miRNA, we grouped all miRNAs according to their diagnostic information that was measured by Mutual Information. Using a subset of 24 miRNAs, a radial basis function Support Vector Machine allowed for discriminating between blood cellsamples of tumor patients and controls with an accuracy of 95.4% [94.9%-95.9%], a specificity of 98.1% [97.3%-98.8%], and a sensitivity of 92.5% [91.8%-92.5%]. Our findings support the idea that neoplasia may lead to a deregulation of miRNA expression in blood cells of cancer patients compared to blood cells of healthy individuals. Furthermore, we provide evidence that miRNA patterns can be used to detect human cancers from blood cells

Identification of microRNAs and long non-coding RNAs involved in fatty acid biosynthesis in tree peony seeds.

Science.gov (United States)

Yin, Dan-Dan; Li, Shan-Shan; Shu, Qing-Yan; Gu, Zhao-Yu; Wu, Qian; Feng, Cheng-Yong; Xu, Wen-Zhong; Wang, Liang-Sheng

2018-08-05

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) act as important molecular regulators in a wide range of biological processes during plant development and seed formation, including oil production. Tree peony seeds contain >90% unsaturated fatty acids (UFAs) and high proportions of α-linolenic acid (ALA, > 40%). To dissect the non-coding RNAs (ncRNAs) pathway involved in fatty acids synthesis in tree peony seeds, we construct six small RNA libraries and six transcriptome libraries from developing seeds of two cultivars (J and S) containing different content of fatty acid compositions. After deep sequencing the RNA libraries, the ncRNA expression profiles of tree peony seeds in two cultivars were systematically and comparatively analyzed. A total of 318 known and 153 new miRNAs and 22,430 lncRNAs were identified, among which 106 conserved and 9 novel miRNAs and 2785 lncRNAs were differentially expressed between the two cultivars. In addition, potential target genes of the microRNA and lncRNAs were also predicted and annotated. Among them, 9 miRNAs and 39 lncRNAs were predicted to target lipid related genes. Results showed that all of miR414, miR156b, miR2673b, miR7826, novel-m0027-5p, TR24651|c0_g1, TR24544|c0_g15, and TR27305|c0_g1 were up-regulated and expressed at a higher level in high-ALA cultivar J when compared to low-ALA cultivar S, suggesting that these ncRNAs and target genes are possibly involved in different fatty acid synthesis and lipid metabolism through post-transcriptional regulation. These results provide a better understanding of the roles of ncRNAs during fatty acid biosynthesis and metabolism in tree peony seeds. Copyright © 2018 Elsevier B.V. All rights reserved.

MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis

Science.gov (United States)

Rothchild, Alissa C.; Sissons, James R.; Shafiani, Shahin; Plaisier, Christopher; Min, Deborah; Mai, Dat; Gilchrist, Mark; Peschon, Jacques; Larson, Ryan P.; Bergthaler, Andreas; Baliga, Nitin S.; Urdahl, Kevin B.; Aderem, Alan

2016-01-01

The regulation of host–pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155–induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment. PMID:27681624

Panning for Long Noncoding RNAs

Directory of Open Access Journals (Sweden)

Li Yang

2013-02-01

Full Text Available The recent advent of high-throughput approaches has revealed widespread transcription of the human genome, leading to a new appreciation of transcription regulation, especially from noncoding regions. Distinct from most coding and small noncoding RNAs, long noncoding RNAs (lncRNAs are generally expressed at low levels, are less conserved and lack protein-coding capacity. These intrinsic features of lncRNAs have not only hampered their full annotation in the past several years, but have also generated controversy concerning whether many or most of these lncRNAs are simply the result of transcriptional noise. Here, we assess these intrinsic features that have challenged lncRNA discovery and further summarize recent progress in lncRNA discovery with integrated methodologies, from which new lessons and insights can be derived to achieve better characterization of lncRNA expression regulation. Full annotation of lncRNA repertoires and the implications of such annotation will provide a fundamental basis for comprehensive understanding of pervasive functions of lncRNAs in biological regulation.

Tuberculosis: General Information

Science.gov (United States)

TB Elimination Tuberculosis: General Information What is TB? Tuberculosis (TB) is a disease caused by germs that are spread from person ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination CS227840_A What Does a Positive Test ...

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs.

Science.gov (United States)

Miesen, Pascal; Ivens, Alasdair; Buck, Amy H; van Rij, Ronald P

2016-02-01

In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of the antiviral RNA interference machinery, one of the key pathways that limit virus replication in invertebrates. Besides siRNAs, Aedes mosquitoes and cells derived from these insects produce arbovirus-derived piRNAs, the best studied examples being viruses from the Togaviridae or Bunyaviridae families. Host miRNAs modulate the expression of a large number of genes and their levels may change in response to viral infections. In addition, some viruses, mostly with a DNA genome, express their own miRNAs to regulate host and viral gene expression. Here, we perform a comprehensive analysis of both viral and host-derived small RNAs in Aedes aegypti Aag2 cells infected with dengue virus 2 (DENV), a member of the Flaviviridae family. Aag2 cells are competent in producing all three types of small RNAs and provide a powerful tool to explore the crosstalk between arboviral infection and the distinct RNA silencing pathways. Interestingly, besides the well-characterized DENV-derived siRNAs, a specific population of viral piRNAs was identified in infected Aag2 cells. Knockdown of Piwi5, Ago3 and, to a lesser extent, Piwi6 results in reduction of vpiRNA levels, providing the first genetic evidence that Aedes PIWI proteins produce DENV-derived small RNAs. In contrast, we do not find convincing evidence for the production of virus-derived miRNAs. Neither do we find that host miRNA expression is strongly changed upon DENV2 infection. Finally, our deep-sequencing analyses detect 30 novel Aedes miRNAs, complementing the repertoire of regulatory small RNAs in this important vector species.

Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder.

Directory of Open Access Journals (Sweden)

Zhifen Liu

Full Text Available LncRNAs, which represent one of the most highly expressed classes of ncRNAs in the brain, are becoming increasingly interesting with regard to brain functions and disorders. However, changes in the expression of regulatory lncRNAs in Major Depressive Disorder (MDD have not yet been reported. Using microarrays, we profiled the expression of 34834 lncRNAs and 39224 mRNAs in peripheral blood sampled from MDD patients as well as demographically-matched controls. Among these, we found that 2007 lncRNAs and 1667 mRNAs were differentially expressed, 17 of which were documented as depression-related gene in previous studies. Gene Ontology (GO and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to fundamental metabolic processes and neurodevelopment diseases. To investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, we also constructed co-expression networks composed of the lncRNAs and mRNAs, which shows significant correlated patterns of expression. In the MDD-derived network, there were a greater number of nodes and connections than that in the control-derived network. The lncRNAs located at chr10:874695-874794, chr10:75873456-75873642, and chr3:47048304-47048512 may be important factors regulating the expression of mRNAs as they have previously been reported associations with MDD. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in MDD using microarray technology. We identified circulating lncRNAs that are aberrantly expressed in MDD and the results suggest that lncRNAs may contribute to the molecular pathogenesis of MDD.

Tuberculosis--triumph and tragedy.

Science.gov (United States)

Singh, M M

2003-03-01

Tuberculosis has been making havoc worldwide with an 11.9 million cases to be involved by the year 2005. In India, about 2 million cases are infected every year. Regarding triumphs and tragedies in the control of tuberculosis some points as follows are discussed. (1) Tuberculosis Control Programmes from National Tuberculosis Programme (NTP) to Revised National Tuberculosis Control Programme (RNTCP) and Directly Observed Treatment, Short course (DOTS). (2) Problem of multidrug resistance (MDR) tuberculosis and (3) HIV and tuberculosis. DOTS being largely based on Indian research. It is now being applied worldwide. MDR is strictly a man made problem. Poor prescriptions, poor case management, lack of coordinated education and haphazard treatment research result in drug resistance. Treatment of MDR is difficult. The drug acceptability, tolerance and toxicity have to be considered. HIV and tuberculosis form a deadly duo. They mean more cases, more costs and more national losses.

Long non-coding RNAs and mRNAs profiling during spleen development in pig.

Science.gov (United States)

Che, Tiandong; Li, Diyan; Jin, Long; Fu, Yuhua; Liu, Yingkai; Liu, Pengliang; Wang, Yixin; Tang, Qianzi; Ma, Jideng; Wang, Xun; Jiang, Anan; Li, Xuewei; Li, Mingzhou

2018-01-01

Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar. A total of 15,040 lncRNA transcripts were identified among these samples. We found that the temporal expression pattern of lncRNAs was more restricted than observed for protein-coding genes. Time-series analysis showed two large modules for protein-coding genes and lncRNAs. The up-regulated module was enriched for genes related to immune and inflammatory function, while the down-regulated module was enriched for cell proliferation processes such as cell division and DNA replication. Co-expression networks indicated the functional relatedness between protein-coding genes and lncRNAs, which were enriched for similar functions over the series of time points examined. We identified numerous differentially expressed protein-coding genes and lncRNAs in all five developmental stages. Notably, ceruloplasmin precursor (CP), a protein-coding gene participating in antioxidant and iron transport processes, was differentially expressed in all stages. This study provides the first catalog of the developing pig spleen, and contributes to a fuller understanding of the molecular mechanisms underpinning mammalian spleen development.

Tumor-like tuberculosis

International Nuclear Information System (INIS)

Kim, Soon Yong

1975-01-01

It was known that some of the abdominal tuberculosis can produce tumor-like appearance clinically and radiologically. But these were mainly masses formed in mesenteric and retroperitoneal lymph nodes. The author has experienced the gastrointestinal tuberculosis resembling to a neoplastic process. In the gastric tuberculosis, irregular narrowing and filling defect with mucosal distortion and occasional shoulder effect could be seen in pyloric antrum. Deformity of proximal portion of duodenum was noted in most cases. Difficulty in differential diagnosis from the gastric cancer might be encountered. If duodenum was not involved. No definite sign of mucosal destruction involved area and associated deformity of duodenum was suggestive of an inflammatory lesion. If there is any tuberculous changes in small bowel, than gastric tuberculosis is more likely. There was the tuberculosis of descending duodenum or pancreaticoduodenal group of lymph nodes revealed cancer-like appearance. Long irregular narrowing with nodular filling defect and mucosal distortion or inverted 3 sign was evident. Differential diagnosis from cancer in duodenum or pancreas could not be made radiographically. Short annular stenosis and nodular filling defect with shoulder effect in both ends of stenosis was noted in some of small bowel tuberculosis. The findings were very resemble to malignancy. There was a case of huge hepatoma-like tuberculosis formed a large irregular mass by lymph nodes and adjacent organs. Chest film was not much help in the differential diagnosis. In many cases of the gastrointestinal tuberculosis, radiological findings were resembled to a neoplastic process. Since none of radiologic findings are specific enough to allow one to make a definitive diagnosis of the gastrointestinal tuberculosis and since type of the gastrointestinal tuberculosis could be cured by chemotherapy, careful analyzation of clinical features is emphasized before surgery.

Tumor-like tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Kim, Soon Yong [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

1975-06-15

It was known that some of the abdominal tuberculosis can produce tumor-like appearance clinically and radiologically. But these were mainly masses formed in mesenteric and retroperitoneal lymph nodes. The author has experienced the gastrointestinal tuberculosis resembling to a neoplastic process. In the gastric tuberculosis, irregular narrowing and filling defect with mucosal distortion and occasional shoulder effect could be seen in pyloric antrum. Deformity of proximal portion of duodenum was noted in most cases. Difficulty in differential diagnosis from the gastric cancer might be encountered. If duodenum was not involved. No definite sign of mucosal destruction involved area and associated deformity of duodenum was suggestive of an inflammatory lesion. If there is any tuberculous changes in small bowel, than gastric tuberculosis is more likely. There was the tuberculosis of descending duodenum or pancreaticoduodenal group of lymph nodes revealed cancer-like appearance. Long irregular narrowing with nodular filling defect and mucosal distortion or inverted 3 sign was evident. Differential diagnosis from cancer in duodenum or pancreas could not be made radiographically. Short annular stenosis and nodular filling defect with shoulder effect in both ends of stenosis was noted in some of small bowel tuberculosis. The findings were very resemble to malignancy. There was a case of huge hepatoma-like tuberculosis formed a large irregular mass by lymph nodes and adjacent organs. Chest film was not much help in the differential diagnosis. In many cases of the gastrointestinal tuberculosis, radiological findings were resembled to a neoplastic process. Since none of radiologic findings are specific enough to allow one to make a definitive diagnosis of the gastrointestinal tuberculosis and since type of the gastrointestinal tuberculosis could be cured by chemotherapy, careful analyzation of clinical features is emphasized before surgery.

Host-directed therapy of tuberculosis: what is in it for microRNA?

Science.gov (United States)

Iannaccone, Marco; Dorhoi, Anca; Kaufmann, Stefan H E

2014-05-01

Tuberculosis (TB) is a major health threat and current intervention measures are far from satisfactory. MicroRNAs (miRs) have become major targets of investigations for different diseases due to their propensity to regulate gene expression in various biological processes. More recently, miRs have been found to play key roles in the control of infectious diseases. Consequently, the potential of miRs for diagnosis and therapy of TB is being considered. In this editorial, we discuss most recent lines of evidence for regulation of the immune response in TB by miRs that could form the basis for diagnosis and host-directed therapy in adjunct to canonical intervention measures in TB.

Imaging in Tuberculosis abdominal

International Nuclear Information System (INIS)

Suarez, Tatiana; Garcia, Vanessa; Tamara, Estrada; Acosta, Federico

2010-01-01

In this article we illustrate and discuss imaging features resulting from Tuberculosis abdominal affectation. We present patients evaluated with several imaging modalities who had abdominal symptoms and findings suggestive of granulomatous disease. Diagnosis was confirm including hystopatology and clinical outgoing. Cases involved presented many affected organs such as lymphatic system, peritoneum, liver, spleen, pancreas, kidneys, ureters, adrenal glands and pelvic organs Tuberculosis, Tuberculosis renal, Tuberculosis hepatic, Tuberculosis splenic Tomography, x-ray, computed

Tuberculosis

OpenAIRE

Latorre Tortello, Pablo

2011-01-01

Por definición, la tuberculosis pulmonar es la localizaci6n del M. tuberculosis en el tracto respiratorio, la forma más común y principal de la afección y la única capaz de contagiar a otras personas. El M. tuberculosis, descubierto por Robert Koch en 1882, el bacilo de Koch, es un bacilo delgado, inmóvil, de 4 micras de longitud media, aerobio obligado, que se tiñe de rajo por la tinción de Ziehl-Neelsen. Debido a la coraza lipídica de su pared, lo hace resistente a la decoloración con ácido...

Tuberculosis

OpenAIRE

Pablo Latorre Tortello

1998-01-01

Por definición, la tuberculosis pulmonar es la localizaci6n del M. tuberculosis en el tracto respiratorio, la forma más común y principal de la afección y la única capaz de contagiar a otras personas. El M. tuberculosis, descubierto por Robert Koch en 1882, el bacilo de Koch, es un bacilo delgado, inmóvil, de 4 micras de longitud media, aerobio obligado, que se tiñe de rajo por la tinción de Ziehl-Neelsen. Debido a la coraza lipídica de su pared, lo hace resistente a la decoloración con ácido...

Role of Small RNAs in Trypanosomatid Infections

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Linhares-Lacerda, Leandra; Morrot, Alexandre

2016-01-01

Trypanosomatid parasites survive and replicate in the host by using mechanisms that aim to establish a successful infection and ensure parasite survival. Evidence points to microRNAs as new players in the host-parasite interplay. MicroRNAs are small non-coding RNAs that control proteins levels via post-transcriptional gene down-regulation, either within the cells where they were produced or in other cells via intercellular transfer. These microRNAs can be modulated in host cells during infection and are among the growing group of small regulatory RNAs, for which many classes have been described, including the transfer RNA-derived small RNAs. Parasites can either manipulate microRNAs to evade host-driven damage and/or transfer small RNAs to host cells. In this mini-review, we present evidence for the involvement of small RNAs, such as microRNAs, in trypanosomatid infections which lack RNA interference. We highlight both microRNA profile alterations in host cells during those infections and the horizontal transfer of small RNAs and proteins from parasites to the host by membrane-derived extracellular vesicles in a cell communication mechanism. PMID:27065454

miRNAs in Normal and Malignant Hematopoiesis

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Ryutaro Kotaki

2017-07-01

Full Text Available Lineage specification is primarily regulated at the transcriptional level and lineage-specific transcription factors determine cell fates. MicroRNAs (miRNAs are 18–24 nucleotide-long non-coding RNAs that post-transcriptionally decrease the translation of target mRNAs and are essential for many cellular functions. miRNAs also regulate lineage specification during hematopoiesis. This review highlights the roles of miRNAs in B-cell development and malignancies, and discusses how miRNA expression profiles correlate with disease prognoses and phenotypes. We also discuss the potential for miRNAs as therapeutic targets and diagnostic tools for B-cell malignancies.

Tuberculosis abdominal Abdominal tuberculosis

OpenAIRE

T. Rubio; M. T. Gaztelu; A. Calvo; M. Repiso; H. Sarasíbar; F. Jiménez Bermejo; A. Martínez Echeverría

2005-01-01

La tuberculosis abdominal cursa con un cuadro inespecífico, con difícil diagnóstico diferencial respecto a otras entidades de similar semiología. Presentamos el caso de un varón que ingresa por presentar dolor abdominal, pérdida progresiva y notoria de peso corporal y fiebre de dos meses de evolución. El cultivo de la biopsia de colon mostró presencia de bacilo de Koch.Abdominal tuberculosis develops according to a non-specific clinical picture, with a difficult differential diagnosis with re...

An expanding universe of noncoding RNAs.

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Storz, Gisela

2002-05-17

Noncoding RNAs (ncRNAs) have been found to have roles in a great variety of processes, including transcriptional regulation, chromosome replication, RNA processing and modification, messenger RNA stability and translation, and even protein degradation and translocation. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined. These findings raise several fundamental questions: How many ncRNAs are encoded by a genome? Given the absence of a diagnostic open reading frame, how can these genes be identified? How can all the functions of ncRNAs be elucidated?

Micro-RNAs

DEFF Research Database (Denmark)

Taipaleenmäki, H.; Hokland, L. B.; Chen, Li

2012-01-01

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed microRNAs has been identified as playing an important role in the regulation of many aspects of osteoblast biology...... including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of microRNA biology and their role in bone formation...

Non-Coding RNAs in Hodgkin Lymphoma

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Anna Cordeiro

2017-05-01

Full Text Available MicroRNAs (miRNAs, small non-coding RNAs that regulate gene expression by binding to the 3’-UTR of their target genes, can act as oncogenes or tumor suppressors. Recently, other types of non-coding RNAs—piwiRNAs and long non-coding RNAs—have also been identified. Hodgkin lymphoma (HL is a B cell origin disease characterized by the presence of only 1% of tumor cells, known as Hodgkin and Reed-Stenberg (HRS cells, which interact with the microenvironment to evade apoptosis. Several studies have reported specific miRNA signatures that can differentiate HL lymph nodes from reactive lymph nodes, identify histologic groups within classical HL, and distinguish HRS cells from germinal center B cells. Moreover, some signatures are associated with survival or response to chemotherapy. Most of the miRNAs in the signatures regulate genes related to apoptosis, cell cycle arrest, or signaling pathways. Here we review findings on miRNAs in HL, as well as on other non-coding RNAs.

Comparative analysis of Mycobacterium and related Actinomycetes yields insight into the evolution of Mycobacterium tuberculosis pathogenesis.

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McGuire, Abigail Manson; Weiner, Brian; Park, Sang Tae; Wapinski, Ilan; Raman, Sahadevan; Dolganov, Gregory; Peterson, Matthew; Riley, Robert; Zucker, Jeremy; Abeel, Thomas; White, Jared; Sisk, Peter; Stolte, Christian; Koehrsen, Mike; Yamamoto, Robert T; Iacobelli-Martinez, Milena; Kidd, Matthew J; Maer, Andreia M; Schoolnik, Gary K; Regev, Aviv; Galagan, James

2012-03-28

The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.

Duodenal tuberculosis

International Nuclear Information System (INIS)

Mirza, M.R.; Sarwar, M.

2004-01-01

Tuberculosis is a world wide communicable disease caused by tubercle bacilli discovered by Robert Kock in 1882. In 1993 WHO declared TB as a global emergency due to its world wide resurgence. It can involve any organ of the body. Abdomen is the fourth commonest site of involvement in the extra pulmonary tuberculosis after the lymph-nodes, skeletal and Genito urinary variants. In the gastro intestinal tract tuberculosis can affect any part from the mouth to the anus but ileocaecal area is a favourite location. Duodenal involvement is uncommon and accounts for only 2.5% of tuberculous enteritis. Major pathogens are Mycobacterium Tuberculosis and bovis and the usual route of entry is by direct penetration of the intestinal mucosa by swallowed organisms. (author)

A survey of small RNAs in human sperm

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Krawetz, Stephen A.; Kruger, Adele; Lalancette, Claudia; Tagett, Rebecca; Anton, Ester; Draghici, Sorin; Diamond, Michael P.

2011-01-01

BACKGROUND There has been substantial interest in assessing whether RNAs (mRNAs and sncRNAs, i.e. small non-coding) delivered from mammalian spermatozoa play a functional role in early embryo development. While the cadre of spermatozoal mRNAs has been characterized, comparatively little is known about the distribution or function of the estimated 24 000 sncRNAs within each normal human spermatozoon. METHODS RNAs of libraries for Next Generation Sequencing. Known sncRNAs that uniquely mapped to a single location in the human genome were identified. RESULTS Bioinformatic analysis revealed the presence of multiple classes of small RNAs in human spermatozoa. The primary classes resolved included microRNA (miRNAs) (≈7%), Piwi-interacting piRNAs (≈17%), repeat-associated small RNAs (≈65%). A minor subset of short RNAs within the transcription start site/promoter fraction (≈11%) frames the histone promoter-associated regions enriched in genes of early embryonic development. These have been termed quiescent RNAs. CONCLUSIONS A complex population of male derived sncRNAs that are available for delivery upon fertilization was revealed. Sperm miRNA-targeted enrichment in the human oocyte is consistent with their role as modifiers of early post-fertilization. The relative abundance of piRNAs and repeat-associated RNAs suggests that they may assume a role in confrontation and consolidation. This may ensure the compatibility of the genomes at fertilization. PMID:21989093

Tuberculosis Fluoroscopy

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Follow-up though Dec 31, 2002 has been completed for a study of site-specific cancer mortality among tuberculosis patients treated with artificial lung collapse therapy in Massachusetts tuberculosis sanatoria (1930-1950).

MicroRNA-27b Modulates Inflammatory Response and Apoptosis during Mycobacterium tuberculosis Infection.

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Liang, Shuxin; Song, Zhigang; Wu, Yongyan; Gao, Yuanpeng; Gao, Mingqing; Liu, Fayang; Wang, Fengyu; Zhang, Yong

2018-04-16

Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs play an important role in regulating host anti-mycobacterial defense; however, their role in apoptosis-mediated mycobacterial elimination and inflammatory response remains unclear. In this study, we explored the role of microRNA-27b (miR-27b) in murine macrophage responses to M. tuberculosis infection. We uncovered that the TLR-2/MyD88/NF-κB signaling pathway induced the expression of miR-27b and miR-27b suppressed the production of proinflammatory factors and the activity of NF-κB, thereby avoiding an excessive inflammation during M. tuberculosis infection. Luciferase reporter assay and Western blotting showed that miR-27b directly targeted Bcl-2-associated athanogene 2 (Bag2) in macrophages. Overexpression of Bag2 reversed miR-27b-mediated inhibition of the production of proinflammatory factors. In addition, miR-27b increased p53-dependent cell apoptosis and the production of reactive oxygen species and decreased the bacterial burden. We also showed that Bag2 interacts with p53 and negatively regulates its activity, thereby controlling cell apoptosis and facilitating bacterial survival. In summary, we revealed a novel role of the miR-27b/Bag2 axis in the regulation of inflammatory response and apoptosis and provide a potential molecular host defense mechanism against mycobacteria. Copyright © 2018 by The American Association of Immunologists, Inc.

miR-582-5p is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO1.

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Liu, Yanhua; Jiang, Jing; Wang, Xinjing; Zhai, Fei; Cheng, Xiaoxing

2013-01-01

Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB). In this study, we found that percentage of apoptotic cells in peripheral blood monocytes from patients with active TB was lower than that from healthy controls (pmicroRNAs can modulate apoptosis of monocytes, we investigated differentially expressed microRNAs in patients with active TB. miR-582-5p was mainly expressed in monocytes and was upregulated in patients with active TB. The apoptotic percentage of THP-1 cells transfected with miR-582-5p mimics was significantly lower than those transfected with negative control of microRNA mimics (pmicroRNA mimics were transfected into THP-1 cells. RT-PCR and western blot analysis showed that the miR-582-5p could suppress both FOXO1 mRNA and protein expression. Co-transfection of miR-582-5p and FOXO1 3'UTR-luciferase reporter vector into cells demonstrated that significant decrease in luciferase activity was only found in reporter vector that contained a wild type sequence of FOXO1 3'UTR, suggesting that miR-582-5p could directly target FOXO1. In conclusion, miR-582-5p inhibited apoptosis of monocytes by down-regulating FOXO1 expression and might play an important role in regulating anti-M. tuberculosis directed immune responses.

The association between smoking and tuberculosis La asociación entre tabaquismo y tuberculosis

Directory of Open Access Journals (Sweden)

K.M. Hassmiller

2006-01-01

Full Text Available OBJECTIVE: To review epidemiological evidence on the association between smoking and tuberculosis. METHODS: Reviewed articles were identified by searching Pubmed for the terms "smoking" or "tobacco" and "tuberculosis". Additional articles were obtained from the bibliographies of identified papers. RESULTS: Thirty-four studies were reviewed: five investigate the association between smoking and mortality from tuberculosis, 13 investigate the association between smoking and development of tuberculosis, eigth investigate the association between smoking and infection with Mycobacterium tuberculosis, and nine estimate the impact of smoking on characteristics of tuberculosis and disease outcomes. CONCLUSIONS: Taken together, evidence suggests that smoking (both current and former is associated with: risk of being infected with Mycobacterium tuberculosis, risk of developing tuberculosis, development of more severe forms of tuberculosis, and risk of dying of tuberculosis. In many cases, there is a strong dose-response relationship -both in terms of quantity and duration of smoking. These relationships are not explained away by controlling for potentially confounding variables such as age, gender, alcohol consumption, and HIV status.OBJETIVO: Revisar evidencia epidemiológica relativa a la asociación entre el tabaquismo y la tuberculosis. MATERIALES Y MÉTODOS: Se identificaron artículos de revisión mediante la búsqueda en Pubmed de los términos "tabaquismo", "tabaco" y "tuberculosis". Se obtuvieron artículos adicionales de las bibliografías de los trabajos identificados. RESULTADOS: Se revisaron 34 estudios: cinco investigan la asociación entre tabaquismo y mortalidad a partir de la tuberculosis; 13, la asociación entre tabaquismo y el desarrollo de tuberculosis; ocho, la asociación entre tabaquismo y la infección con Mycobacterium tuberculosis; y nueve estiman el impacto del tabaquismo en las características de la tuberculosis y las

Genitourinary tuberculosis

International Nuclear Information System (INIS)

Matos, Maria Joao; Bacelar, Maria Teresa; Pinto, Pedro; Ramos, Isabel

2005-01-01

Although uncommon, genitourinary tuberculosis is the most common site of extrapulmonary tuberculosis infection. Its diagnosis is often difficult. This article provides an overview of the pathologic and radiologic findings of this disease process

Drivers of Tuberculosis Transmission.

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Mathema, Barun; Andrews, Jason R; Cohen, Ted; Borgdorff, Martien W; Behr, Marcel; Glynn, Judith R; Rustomjee, Roxana; Silk, Benjamin J; Wood, Robin

2017-11-03

Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Vaccination against tuberculosis.

Science.gov (United States)

Martin, Carlos; Aguilo, Nacho; Gonzalo-Asensio, Jesús

2018-04-04

BCG (Bacille Calmette-Guérin) vaccination is included in the immunization schedule for tuberculosis endemic countries with a global coverage at birth close to 90% worldwide. BCG was attenuated from Mycobacterium bovis almost a century ago, and provides a strong protection against disseminated forms of the disease, though very limited against pulmonary forms of tuberculosis, responsible for transmission. Novel prophylactic tuberculosis vaccines are in clinical development either to replace BCG or to improve its protection against respiratory forms of the disease. There are limitations understanding the immunological responses involved and the precise type of long-lived immunity that new vaccines need to induce. MTBVAC is the first and only tuberculosis vaccine candidate based on live-attenuated Mycobacterium tuberculosis in clinical evaluation. MTBVAC clinical development plans to target tuberculosis prevention in newborns, as a BCG replacement strategy, and as secondary objective to be tested in adolescents and adults previous vaccinated with BCG. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis.

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Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

2017-01-01

We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.

Childhood tuberculosis and malnutrition.

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Jaganath, Devan; Mupere, Ezekiel

2012-12-15

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease.

Endogenous small RNAs and antibacterial immunity in plants.

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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.

Global Tuberculosis Report 2016

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... Alt+0 Navigation Alt+1 Content Alt+2 Tuberculosis (TB) Menu Tuberculosis Data and statistics Regional Framework Resources Meetings and events Global tuberculosis report 2017 WHO has published a global TB ...

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

Science.gov (United States)

Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

MicroRNAs in Cardiometabolic Diseases

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Anna Meiliana

2013-08-01

Full Text Available BACKGROUND: MicroRNAs (miRNAs are ~22-nucleotide noncoding RNAs with critical functions in multiple physiological and pathological processes. An explosion of reports on the discovery and characterization of different miRNA species and their involvement in almost every aspect of cardiac biology and diseases has established an exciting new dimension in gene regulation networks for cardiac development and pathogenesis. CONTENT: Alterations in the metabolic control of lipid and glucose homeostasis predispose an individual to develop cardiometabolic diseases, such as type 2 diabetes mellitus and atherosclerosis. Work over the last years has suggested that miRNAs play an important role in regulating these physiological processes. Besides a cell-specific transcription factor profile, cell-specific miRNA-regulated gene expression is integral to cell fate and activation decisions. Thus, the cell types involved in atherosclerosis, vascular disease, and its myocardial sequelae may be differentially regulated by distinct miRNAs, thereby controlling highly complex processes, for example, smooth muscle cell phenotype and inflammatory responses of endothelial cells or macrophages. The recent advancements in using miRNAs as circulating biomarkers or therapeutic modalities, will hopefully be able to provide a strong basis for future research to further expand our insights into miRNA function in cardiovascular biology. SUMMARY: MiRNAs are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. They are potent modulators of diverse biological processes and pathologies. Recent findings demonstrated the importance of miRNAs in the vasculature and the orchestration of lipid metabolism and glucose homeostasis. MiRNA networks represent an additional layer of regulation for gene expression that absorbs perturbations and ensures the robustness of biological systems. A detailed understanding of the molecular and cellular mechanisms of mi

LncRNAs in vertebrates: advances and challenges.

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Mallory, Allison C; Shkumatava, Alena

2015-10-01

Beyond the handful of classic and well-characterized long noncoding RNAs (lncRNAs), more recently, hundreds of thousands of lncRNAs have been identified in multiple species including bacteria, plants and vertebrates, and the number of newly annotated lncRNAs continues to increase as more transcriptomes are analyzed. In vertebrates, the expression of many lncRNAs is highly regulated, displaying discrete temporal and spatial expression patterns, suggesting roles in a wide range of developmental processes and setting them apart from classic housekeeping ncRNAs. In addition, the deregulation of a subset of these lncRNAs has been linked to the development of several diseases, including cancers, as well as developmental anomalies. However, the majority of vertebrate lncRNA functions remain enigmatic. As such, a major task at hand is to decipher the biological roles of lncRNAs and uncover the regulatory networks upon which they impinge. This review focuses on our emerging understanding of lncRNAs in vertebrate animals, highlighting some recent advances in their functional analyses across several species and emphasizing the current challenges researchers face to characterize lncRNAs and identify their in vivo functions. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Rapid Detection and Identification of miRNAs by Surface-Enhanced Raman Spectroscopy Using Hollow Au Nanoflowers Substrates

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Xiaowei Cao

2017-01-01

Full Text Available MicroRNAs (miRNAs are recognized as regulators of gene expression during the biological processes of cells as well as biomarkers of many diseases. Development of rapid and sensitive miRNA profiling methods is crucial for evaluating the pattern of miRNA expression related to normal and diseased states. This work presents a novel hollow Au nanoflowers (HAuNFs substrate for rapid detection and identification of miRNAs by surface-enhanced Raman scattering (SERS spectroscopy. We synthesized the HAuNFs by a seed-mediated growth approach. Then, HAuNFs substrates were fabricated by depositing HAuNFs onto the surfaces of (3-aminopropyltriethoxysilane- (APTES- functionalized ITO glass. The result demonstrated that HAuNFs substrates had very good reproducibility, homogeneous SERS activity, and high SERS effect. The substrates enabled us to successfully obtain the SERS spectra of miR-10a-5p, miR-125a-5p, and miR-196a-5p. The difference spectra among the three kinds of miRNAs were studied to better interpret the spectral differences and identify miRNA expression patterns with high accuracy. The principal component analysis (PCA of the SERS spectra was used to distinguish among the three kinds of miRNAs. Considering its time efficiency, being label-free, and its sensitivity, the SERS based on HAuNFs substrates is very promising for miRNA research and plays an important role in early disease detection and prevention.

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

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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

Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.

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Shi, Jiandong; Sun, Jing; Wu, Meini; Hu, Ningzhu; Hu, Yunzhang

2016-06-01

The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P viral miRNA mimics. Conversely, they were significantly increased (more than 3.3-fold addition, P viral miRNA inhibitors. The luciferase reporter assay of miRNA targets showed that viral miRNAs were fully complementary to specific sites of the viral plus or minus strand RNA and strongly inhibited their expressions. Further data showed that the relative abundance of viral genomic RNA fragments that contain miRNA targets was also dramatically reduced (more than 80 % reduction, P viral miRNAs were overexpressed with miRNA mimics. In contrast, they were significantly increased (approximately 2-fold addition, P viral miRNAs were inhibited with miRNA inhibitors. In conclusion, these data suggest a possible mechanism for the reduction of viral RNA synthesis during HAV infection. Thus, we propose that it is likely that RNA virus-derived miRNA could serve as a self-mediated feedback regulator during infection.

Noncoding RNAs in Cancer Medicine

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Laura Cerchia

2006-01-01

Full Text Available Several signalling proteins involved in cell growth and differentiation represent attractive candidate targets for cancer diagnosis and/or therapy since they can act as oncogenes. Because of their high specificity and low immunogeneicity, using artificial small noncoding RNA (ncRNAs as therapeutics has recently become a highly promising and rapidly expanding field of interest. Indeed, ncRNAs may either interfere with RNA transcription, stability, translation or directly hamper the function of the targets by binding to their surface. The recent finding that the expression of several genes is under the control of small single-stranded regulatory RNAs, including miRNAs, makes these genes as appropriate targets for ncRNA gene silencing. Furthermore, another class of small ncRNA, aptamers, act as high-affinity ligands and potential antagonists of disease-associated proteins. We will review here the recent and innovative methods that have been developed and the possible applications of ncRNAs as inhibitors or tracers in cancer medicine.

The Host RNAs in Retroviral Particles

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Alice Telesnitsky

2016-08-01

Full Text Available As they assemble, retroviruses encapsidate both their genomic RNAs and several types of host RNA. Whereas limited amounts of messenger RNA (mRNA are detectable within virion populations, the predominant classes of encapsidated host RNAs do not encode proteins, but instead include endogenous retroelements and several classes of non-coding RNA (ncRNA, some of which are packaged in significant molar excess to the viral genome. Surprisingly, although the most abundant host RNAs in retroviruses are also abundant in cells, unusual forms of these RNAs are packaged preferentially, suggesting that these RNAs are recruited early in their biogenesis: before associating with their cognate protein partners, and/or from transient or rare RNA populations. These RNAs’ packaging determinants differ from the viral genome’s, and several of the abundantly packaged host ncRNAs serve cells as the scaffolds of ribonucleoprotein particles. Because virion assembly is equally efficient whether or not genomic RNA is available, yet RNA appears critical to the structural integrity of retroviral particles, it seems possible that the selectively encapsidated host ncRNAs might play roles in assembly. Indeed, some host ncRNAs appear to act during replication, as some transfer RNA (tRNA species may contribute to nuclear import of human immunodeficiency virus 1 (HIV-1 reverse transcription complexes, and other tRNA interactions with the viral Gag protein aid correct trafficking to plasma membrane assembly sites. However, despite high conservation of packaging for certain host RNAs, replication roles for most of these selectively encapsidated RNAs—if any—have remained elusive.

miRNAs and other non-coding RNAs in posttraumatic stress disorder: A systematic review of clinical and animal studies.

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Schmidt, Ulrike; Keck, Martin E; Buell, Dominik R

2015-06-01

In the last couple of years, non-coding (nc) RNAs like micro-RNAs (miRNAs), small interference RNAs (siRNAs) and long ncRNAs (lncRNAs) have emerged as promising candidates for biomarkers and drug-targets in a variety of psychiatric disorders. In contrast to reports on ncRNAs in affective disorders, schizophrenia and anxiety disorders, manuscripts on ncRNAs in posttraumatic stress disorder (PTSD) and associated animal models are scarce. Aiming to stimulate ncRNA research in PTSD and to identify the hitherto most promising ncRNA candidates and associated pathways for psychotrauma research, we conducted the first review on ncRNAs in PTSD. We aimed to identify studies reporting on the expression, function and regulation of ncRNAs in PTSD patients and in animals exhibiting a PTSD-like syndrome. Following the PRISMA guidelines for systematic reviews, we systematically screened the PubMed database for clinical and animal studies on ncRNAs in PTSD, animal models for PTSD and animal models employing a classical fear conditioning paradigm. Using 112 different combinations of search terms, we retrieved 523 articles of which we finally included and evaluated three clinical and 12 animal studies. In addition, using the web-based tool DIANA miRPath v2.0, we searched for molecular pathways shared by the predicted targets of the here-evaluated miRNA candidates. Our findings suggest that mir-132, which has been found to be regulated in three of the here included studies, as well as miRNAs with an already established role in Alzheimer's disease (AD) seem to be particularly promising candidates for future miRNA studies in PTSD. These results are limited by the low number of human trials and by the heterogeneity of included animal studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drug therapy in spinal tuberculosis.

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Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Role of Exosomal Noncoding RNAs in Lung Carcinogenesis

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Tao Sun

2015-01-01

Full Text Available Lung cancer is the major cause of cancer death worldwide. Novel, recently discovered classes of noncoding RNAs (ncRNAs have diverse functional and regulatory activities and increasing evidence suggests crucial roles for deregulated ncRNAs in the onset and progression of cancer, including lung cancer. Exosomes are small extracellular membrane vesicles of endocytic origin that are released by many cells and are found in most body fluids. Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth and metastasis. MicroRNAs (miRNAs are a subclass of ncRNAs that are present in exosomes. miRNAs are taken up by neighboring or distant cells and modulate various functions of recipient cells. Here, we review exosome-derived ncRNAs with a focus on miRNAs and their role in lung cancer biology.

Tuberculosis as occupational disease

OpenAIRE

Mendoza-Ticona, Alberto; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia. Lima, Perú. Médico infectólogo tropicalista magister en Epidemiología Clínica.

2014-01-01

There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupationa...

Cerebellar neurodegeneration in the absence of microRNAs

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Schaefer, Anne; O'Carroll, Dónal; Tan, Chan Lek; Hillman, Dean; Sugimori, Mutsuyuki; Llinas, Rodolfo; Greengard, Paul

2007-01-01

Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell–specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders. PMID:17606634

Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.

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Kim, Sung-Han; Kim, Mi Young; Hong, Sun In; Jung, Jiwon; Lee, Hyun Joo; Yun, Sung-Cheol; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee

2015-07-01

Pulmonary tuberculosis is occasionally confused with invasive pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging modes such as computed tomography (CT). We therefore investigated IPA-mimicking tuberculosis in transplant recipients. All adult transplant recipients who developed tuberculosis or IPA at a tertiary hospital in an intermediate tuberculosis-burden country during a 6-year period were enrolled. First, we tested whether experienced radiologists could differentiate pulmonary tuberculosis from IPA. Second, we determined which radiologic findings could help us differentiate them. During the study period, 28 transplant recipients developed pulmonary tuberculosis after transplantation, and 80 patients developed IPA after transplantation. Two experienced radiologists scored blindly 28 tuberculosis and 50 randomly selected IPA cases. The sensitivities of radiologists A and B for IPA were 78% and 68%, respectively (poor agreement, kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then compared the CT findings of the 28 patients with tuberculosis and 80 patients with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were more frequent in IPA, and mass-shaped consolidations and centrilobular nodules (tuberculosis. Certain CT findings appear to be helpful in differentiating between IPA and tuberculosis. Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases in transplant recipients are very close to those of IPA. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Regulatory Role of Circular RNAs and Neurological Disorders.

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Floris, Gabriele; Zhang, Longbin; Follesa, Paolo; Sun, Tao

2017-09-01

Circular RNAs (circRNAs) are a class of long noncoding RNAs that are characterized by the presence of covalently linked ends and have been found in all life kingdoms. Exciting studies in regulatory roles of circRNAs are emerging. Here, we summarize classification, characteristics, biogenesis, and regulatory functions of circRNAs. CircRNAs are found to be preferentially expressed along neural genes and in neural tissues. We thus highlight the association of circRNA dysregulation with neurodegenerative diseases such as Alzheimer's disease. Investigation of regulatory role of circRNAs will shed novel light in gene expression mechanisms during development and under disease conditions and may identify circRNAs as new biomarkers for aging and neurodegenerative disorders.

Extracellular small RNAs: what, where, why?

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Hoy, Anna M.; Buck, Amy H.

2012-01-01

miRNAs (microRNAs) are a class of small RNA that regulate gene expression by binding to mRNAs and modulating the precise amount of proteins that get expressed in a cell at a given time. This form of gene regulation plays an important role in developmental systems and is critical for the proper function of numerous biological pathways. Although miRNAs exert their functions inside the cell, these and other classes of RNA are found in body fluids in a cell-free form that is resistant to degradation by RNases. A broad range of cell types have also been shown to secrete miRNAs in association with components of the RISC (RNA-induced silencing complex) and/or encapsulation within vesicles, which can be taken up by other cells. In the present paper, we provide an overview of the properties of extracellular miRNAs in relation to their capacity as biomarkers, stability against degradation and mediators of cell–cell communication. PMID:22817753

Hidden layers of human small RNAs

DEFF Research Database (Denmark)

Kawaji, Hideya; Nakamura, Mari; Takahashi, Yukari

2008-01-01

small RNA have focused on miRNA and/or siRNA rather than on the exploration of additional classes of RNAs. RESULTS: Here, we explored human small RNAs by unbiased sequencing of RNAs with sizes of 19-40 nt. We provide substantial evidences for the existence of independent classes of small RNAs. Our data......BACKGROUND: Small RNA attracts increasing interest based on the discovery of RNA silencing and the rapid progress of our understanding of these phenomena. Although recent studies suggest the possible existence of yet undiscovered types of small RNAs in higher organisms, many studies to profile...... shows that well-characterized non-coding RNA, such as tRNA, snoRNA, and snRNA are cleaved at sites specific to the class of ncRNA. In particular, tRNA cleavage is regulated depending on tRNA type and tissue expression. We also found small RNAs mapped to genomic regions that are transcribed in both...

MicroRNAs as regulatory elements in psoriasis

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Liu Yuan

2016-01-01

Full Text Available Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.

Global alteration of microRNAs and transposon-derived small RNAs in cotton (Gossypium hirsutum) during Cotton leafroll dwarf polerovirus (CLRDV) infection.

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Romanel, Elisson; Silva, Tatiane F; Corrêa, Régis L; Farinelli, Laurent; Hawkins, Jennifer S; Schrago, Carlos E G; Vaslin, Maite F S

2012-11-01

Small RNAs (sRNAs) are a class of non-coding RNAs ranging from 20- to 40-nucleotides (nts) that are present in most eukaryotic organisms. In plants, sRNAs are involved in the regulation of development, the maintenance of genome stability and the antiviral response. Viruses, however, can interfere with and exploit the silencing-based regulatory networks, causing the deregulation of sRNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). To understand the impact of viral infection on the plant sRNA pathway, we deep sequenced the sRNAs in cotton leaves infected with Cotton leafroll dwarf virus (CLRDV), which is a member of the economically important virus family Luteoviridae. A total of 60 putative conserved cotton miRNAs were identified, including 19 new miRNA families that had not been previously described in cotton. Some of these miRNAs were clearly misregulated during viral infection, and their possible role in symptom development and disease progression is discussed. Furthermore, we found that the 24-nt heterochromatin-associated siRNAs were quantitatively and qualitatively altered in the infected plant, leading to the reactivation of at least one cotton transposable element. This is the first study to explore the global alterations of sRNAs in virus-infected cotton plants. Our results indicate that some CLRDV-induced symptoms may be correlated with the deregulation of miRNA and/or epigenetic networks.

Tuberculosis

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Pablo Latorre Tortello

1998-10-01

Full Text Available Por definición, la tuberculosis pulmonar es la localizaci6n del M. tuberculosis en el tracto respiratorio, la forma más común y principal de la afección y la única capaz de contagiar a otras personas. El M. tuberculosis, descubierto por Robert Koch en 1882, el bacilo de Koch, es un bacilo delgado, inmóvil, de 4 micras de longitud media, aerobio obligado, que se tiñe de rajo por la tinción de Ziehl-Neelsen. Debido a la coraza lipídica de su pared, lo hace resistente a la decoloración con ácidos y alcohol, de ahí el nombre de bacilos ácido-alcohol resistente (BAAR. Su transmisión es directa, de persona a persona.

Non-Coding RNAs: Multi-Tasking Molecules in the Cell

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Anita Quintal Gomes

2013-07-01

Full Text Available In the last years it has become increasingly clear that the mammalian transcriptome is highly complex and includes a large number of small non-coding RNAs (sncRNAs and long noncoding RNAs (lncRNAs. Here we review the biogenesis pathways of the three classes of sncRNAs, namely short interfering RNAs (siRNAs, microRNAs (miRNAs and PIWI-interacting RNAs (piRNAs. These ncRNAs have been extensively studied and are involved in pathways leading to specific gene silencing and the protection of genomes against virus and transposons, for example. Also, lncRNAs have emerged as pivotal molecules for the transcriptional and post-transcriptional regulation of gene expression which is supported by their tissue-specific expression patterns, subcellular distribution, and developmental regulation. Therefore, we also focus our attention on their role in differentiation and development. SncRNAs and lncRNAs play critical roles in defining DNA methylation patterns, as well as chromatin remodeling thus having a substantial effect in epigenetics. The identification of some overlaps in their biogenesis pathways and functional roles raises the hypothesis that these molecules play concerted functions in vivo, creating complex regulatory networks where cooperation with regulatory proteins is necessary. We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer.

Radiologic diagnosis of lung tuberculosis

International Nuclear Information System (INIS)

Eisenhuber, E.; Mostbeck, G.; Bankier, A.; Stadler, A.; Rumetshofer, R.

2007-01-01

The radiologic knowledge of tuberculosis-associated lung disease is an essential tool in the clinical diagnosis of tuberculosis. Chest radiography is the primary imaging method, but the importance of CT is still increasing, as CT is more sensitive in the detection of cavitation, of hilar and mediastinal lymphadenopathie, of endobronchial spread and of complications in the course of the disease. In addition, CT has been proven as a valuable technique in the assessment of tuberculosis activity, especially in patients where M. tuberculosis has not been detected in the sputum or in patients with multidrug-resistant tuberculosis. Depending on the immune status of the patient, the morphologic spectrum of tuberculosis is quite variable. Early diagnosis of tuberculosis is essential to prevent further spread of the disease. (orig.) [de

[Increased IL-4 production in response to virulent Mycobacterium tuberculosis in tuberculosis patients with advanced disease].

Science.gov (United States)

Ordway, Diane J; Martins, Marta S; Costa, Leonor M; Freire, Mónica S; Arroz, Maria J; Dockrell, Hazel M; Ventura, Fernando A

2005-01-01

The study was designed to compare immune responses to Mycobacterium tuberculosis bacilli and antigens in healthy Portuguese subjects and pulmonary tuberculosis patients (TB), and to correlate immune status with clinical severity of tuberculosis disease. PBMC were cultured and stimulated with live and killed M. tuberculosis H37Rv and purified protein derivative (PPD) and lymphoproliferation and production of IFN-gamma and IL-5/IL-4 by these cultures were evaluated by the use of ELISA and multi-parameter flow cytometry. PBMC from 30 tuberculosis patients demonstrated significantly reduced amounts of proliferation and IFN-gamma when stimulated with live M. tuberculosis compared the control group. Of 15 tuberculosis patients tested for intracellular IL-4 following stimulation with M. tuberculosis, 7 showed greatly increased IL-4 production in CD8+ and gammadelta+ T cells. Tuberculosis patients demonstrated an increase of intracellular IL-4 after PBMC were stimulated with live M. tuberculosis in the CD4+ phenotype, but more notably in CD8+ and gammadelta TCR+ subsets. Increased production of IL-4 in tuberculosis patients was primarily in individuals with advanced involvement of lung parenchymal with high bacterial loads in sputum. These results suggest that an alteration in type 1 and type 2 cytokine balance can occur in patients with tuberculosis at an advanced clinical stage of disease.

Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia

NARCIS (Netherlands)

de Jong, Bouke C.; Hill, Philip C.; Aiken, Alex; Awine, Timothy; Antonio, Martin; Adetifa, Ifedayo M.; Jackson-Sillah, Dolly J.; Fox, Annette; Deriemer, Kathryn; Gagneux, Sebastien; Borgdorff, Martien W.; McAdam, Keith P. W. J.; Corrah, Tumani; Small, Peter M.; Adegbola, Richard A.

2008-01-01

BACKGROUND: There is considerable variability in the outcome of Mycobacterium tuberculosis infection. We hypothesized that Mycobacterium africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. METHODS: In a cohort study of patients with tuberculosis and their

Base Composition Characteristics of Mammalian miRNAs

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Bin Wang

2013-01-01

Full Text Available MicroRNAs (miRNAs are short RNA sequences that repress protein synthesis by either inhibiting the translation of messenger RNA (mRNA or increasing mRNA degradation. Endogenous miRNAs have been found in various organisms, including animals, plants, and viruses. Mammalian miRNAs are evolutionarily conserved, are scattered throughout chromosomes, and play an important role in the immune response and the onset of cancer. For this study, the author explored the base composition characteristics of miRNA genes from the six mammalian species that contain the largest number of known miRNAs. It was found that mammalian miRNAs are evolutionarily conserved and GU-rich. Interestingly, in the miRNA sequences investigated, A residues are clearly the most frequent occupants of positions 2 and 3 of the 5′ end of miRNAs. Unlike G and U residues that may pair with C/U and A/G, respectively, A residues can only pair with U residues of target mRNAs, which may augment the recognition specificity of the 5′ seed region.

"Impact of and response to increased tuberculosis prevalence among Syrian refugees compared with Jordanian tuberculosis prevalence: case study of a tuberculosis public health strategy".

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Cookson, Susan T; Abaza, Hiba; Clarke, Kevin R; Burton, Ann; Sabrah, Nadia A; Rumman, Khaled A; Odeh, Nedal; Naoum, Marwan

2015-01-01

By the summer of 2014, the Syrian crisis resulted in a regional humanitarian emergency with 2.9 million refugees, including 608,000 in Jordan. These refugees access United Nations High Commissioner for Refugees (UNHCR)-sponsored clinics or Jordan Ministry of Health clinics, including tuberculosis diagnosis and treatment. Tuberculosis care in Syria has deteriorated with destroyed health infrastructure and drug supply chain. Syrian refugees may have undiagnosed tuberculosis; therefore, the UNHCR, the International Organization for Migration (IOM), the National Tuberculosis Program (NTP), and the Centers for Disease Control and Prevention developed the Public Health Strategy for Tuberculosis among Syrian Refugees in Jordan. This case study presents that strategy, its impact, and recommendations for other neighboring countries. UNHCR determined that World Health Organization (WHO) criteria for implementing a tuberculosis program in an emergency were met for the Syrian refugees in Jordan. Jordan NTP assessed their tuberculosis program and found that access to Syrian refugees was the one component of their program missing. Therefore, a strategy for tuberculosis control among Syrian refugees was developed. Since that development through work with IOM, UNHCR, and NTP, tuberculosis case detection among Syrian refugees is almost 40 % greater (74 cases/12 months or 1.01/100,000 monthly through June 2014 vs. 56 cases/16 months or 0.73/100,000 monthly through June 2013) using estimated population figures; more than two fold the 2012 Jordan tuberculosis incidence. Additionally, the WHO objective of curing ≥85 % of newly identified infectious tuberculosis cases was met among Syrian refugees. Tuberculosis (TB) rates among displaced persons are high, but increased detection is possible. High TB rates were found among Syrian refugees through active screening and will probably persist as the Syrian crisis continues. Active screening can detect tuberculosis early and reduce risk

High tuberculosis prevalence in a South African prison: the need for routine tuberculosis screening.

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Lilanganee Telisinghe

Full Text Available Tuberculosis is a major health concern in prisons, particularly where HIV prevalence is high. Our objective was to determine the undiagnosed pulmonary tuberculosis ("undiagnosed tuberculosis" prevalence in a representative sample of prisoners in a South African prison. In addition we investigated risk factors for undiagnosed tuberculosis, to explore if screening strategies could be targeted to high risk groups, and, the performance of screening tools for tuberculosis.In this cross-sectional survey, male prisoners were screened for tuberculosis using symptoms, chest radiograph (CXR and two spot sputum specimens for microscopy and culture. Anonymised HIV antibody testing was performed on urine specimens. The sensitivity, specificity and predictive values of symptoms and investigations were calculated, using Mycobacterium tuberculosis isolated on sputum culture as the gold standard. From September 2009 to October 2010, 1046 male prisoners were offered enrolment to the study. A total of 981 (93.8% consented (median age was 32 years; interquartile range [IQR] 27-37 years and were screened for tuberculosis. Among 968 not taking tuberculosis treatment and with sputum culture results, 34 (3.5%; 95% confidence interval [CI] 2.4-4.9% were culture positive for Mycobacterium tuberculosis. HIV prevalence was 25.3% (242/957; 95% CI 22.6-28.2%. Positive HIV status (adjusted odds ratio [aOR] 2.0; 95% CI 1.0-4.2 and being an ex-smoker (aOR 2.6; 95% CI 1.2-5.9 were independently associated with undiagnosed tuberculosis. Compared to the gold standard of positive sputum culture, cough of any duration had a sensitivity of 35.3% and specificity of 79.6%. CXR was the most sensitive single screening modality (sensitivity 70.6%, specificity 92.2%. Adding CXR to cough of any duration gave a tool with sensitivity of 79.4% and specificity of 73.8%.Undiagnosed tuberculosis and HIV prevalence was high in this prison, justifying routine screening for tuberculosis at entry

Small RNA Sequencing Uncovers New miRNAs and moRNAs Differentially Expressed in Normal and Primary Myelofibrosis CD34+ Cells.

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Paola Guglielmelli

Full Text Available Myeloproliferative neoplasms (MPN are chronic myeloid cancers thought to arise at the level of CD34+ hematopoietic stem/progenitor cells. They include essential thrombocythemia (ET, polycythemia vera (PV and primary myelofibrosis (PMF. All can progress to acute leukemia, but PMF carries the worst prognosis. Increasing evidences indicate that deregulation of microRNAs (miRNAs might plays an important role in hematologic malignancies, including MPN. To attain deeper knowledge of short RNAs (sRNAs expression pattern in CD34+ cells and of their possible role in mediating post-transcriptional regulation in PMF, we sequenced with Illumina HiSeq2000 technology CD34+ cells from healthy subjects and PMF patients. We detected the expression of 784 known miRNAs, with a prevalence of miRNA up-regulation in PMF samples, and discovered 34 new miRNAs and 99 new miRNA-offset RNAs (moRNAs, in CD34+ cells. Thirty-seven small RNAs were differentially expressed in PMF patients compared with healthy subjects, according to microRNA sequencing data. Five miRNAs (miR-10b-5p, miR-19b-3p, miR-29a-3p, miR-379-5p, and miR-543 were deregulated also in PMF granulocytes. Moreover, 3'-moR-128-2 resulted consistently downregulated in PMF according to RNA-seq and qRT-PCR data both in CD34+ cells and granulocytes. Target predictions of these validated small RNAs de-regulated in PMF and functional enrichment analyses highlighted many interesting pathways involved in tumor development and progression, such as signaling by FGFR and DAP12 and Oncogene Induced Senescence. As a whole, data obtained in this study deepened the knowledge of miRNAs and moRNAs altered expression in PMF CD34+ cells and allowed to identify and validate a specific small RNA profile that distinguishes PMF granulocytes from those of normal subjects. We thus provided new information regarding the possible role of miRNAs and, specifically, of new moRNAs in this disease.

The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

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Michal Lubas

2015-01-01

Full Text Available The RNA exosome complex constitutes the major nuclear eukaryotic 3′-5′ exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to some of its substrates by the nuclear exosome targeting (NEXT complex. How NEXT targets RNA has remained elusive. Using an in vivo crosslinking approach, we report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs, enhancer RNAs (eRNAs, and 3′-extended products from snRNA and replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3′ ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT defines an early exosome-targeting pathway for 3′-extended snoRNAs derived from such introns. We propose that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome action in case of available unprotected RNA 3′ ends.

Analysis of peculiarities of identification, diagnostics and course of tuberculosis in patients with tuberculosis/HIV co-infection

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V. P. Melnyk

2017-10-01

Full Text Available Objective – to analyse dynamics of detection of tuberculosis and HIV/AIDS in tuberculosis/HIV co-infection, to identify the main clinical forms of tuberculosis, the type of tuberculosis process and the structure of incidence of tuberculosis, to analyse dependence of a clinical form of tuberculosis on quantity of CD4 cells. Materials and methods. 155 patients with tuberculosis/HIV co-infection and 155 patients with tuberculosis without HIV infection were examined. All patients underwent general clinical examination, laboratory tests, X-ray, microbiological, histological studies (with extrapulmonary tuberculosis. Results. In all patients, co-infection was detected mainly by respiratory tuberculosis (in 73 % of HIV-positive and 89 % of HIV-negative patients. In HIV-positive patients, tuberculosis was more often detected by the passive way (81 %, and in HIV-negative patients – by the active way (78 %. 66.5 % of patients had HIV infection first, 21.3 % had the first tuberculosis, and 12.2 % had HIV infection and tuberculosis at the same time. In clinical forms in patients with HIV-infection, infiltrative and disseminated tuberculosis prevailed. Pulmonary tuberculosis was diagnosed in 70.3 % of patients, extrapulmonary – in 11 %, pulmonary and extrapulmonary tuberculosis – in 18.7 %. In 28.4 % of patients, immunodeficiency was detected with CD4 cells less than 100 in 1mm3, in 22.6 % of patients – 101–200 CD4 cells in 1 mm3, in 10.3 % in 201–300 CD4 in 1 mm3, in 14.8 % of patients – 301–500 CD4 in 1 mm3 and in 23.9 % ≥ 500 CD4 in 1 mm3. In 56.1 % of patients, first diagnosed tuberculosis was detected, 28.4 % had the relapse of tuberculosis, 7.7 % had tuberculosis after a previous ineffective treatment, 7.7 % had tuberculosis with treatment after the break. Bacterial excretion (by the scopic method was detected in 42.6 % of patients, by the bacteriological method – in 73.9 %, by the molecular-genetic method – in 93.2 %, typical

Exploiting tRNAs to Boost Virulence

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Suki Albers

2016-01-01

Full Text Available Transfer RNAs (tRNAs are powerful small RNA entities that are used to translate nucleotide language of genes into the amino acid language of proteins. Their near-uniform length and tertiary structure as well as their high nucleotide similarity and post-transcriptional modifications have made it difficult to characterize individual species quantitatively. However, due to the central role of the tRNA pool in protein biosynthesis as well as newly emerging roles played by tRNAs, their quantitative assessment yields important information, particularly relevant for virus research. Viruses which depend on the host protein expression machinery have evolved various strategies to optimize tRNA usage—either by adapting to the host codon usage or encoding their own tRNAs. Additionally, several viruses bear tRNA-like elements (TLE in the 5′- and 3′-UTR of their mRNAs. There are different hypotheses concerning the manner in which such structures boost viral protein expression. Furthermore, retroviruses use special tRNAs for packaging and initiating reverse transcription of their genetic material. Since there is a strong specificity of different viruses towards certain tRNAs, different strategies for recruitment are employed. Interestingly, modifications on tRNAs strongly impact their functionality in viruses. Here, we review those intersection points between virus and tRNA research and describe methods for assessing the tRNA pool in terms of concentration, aminoacylation and modification.

Gastrointestinal tuberculosis.

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Galloway, D J; Scott, R N

1986-10-01

In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

MicroRNA-encoding long non-coding RNAs

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Zhu Xiaopeng

2008-05-01

Full Text Available Abstract Background Recent analysis of the mouse transcriptional data has revealed the existence of ~34,000 messenger-like non-coding RNAs (ml-ncRNAs. Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. Results A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 × 10-16 with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800 in the ml-ncRNAs population. Conclusion Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.

The Roles of MicroRNAs in Breast Cancer

International Nuclear Information System (INIS)

Takahashi, Ryou-u; Miyazaki, Hiroaki; Ochiya, Takahiro

2015-01-01

MicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide, non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. In various cancers, miRNAs play important roles in tumor initiation, drug resistance and metastasis. Recent studies reported that miRNAs could also be secreted via small endosome-derived vesicles called exosomes, which are derived from multiple cell types, including dendritic cells, lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to-cell communication and have been investigated as prognostic and diagnostic biomarkers. In this review, we summarize the major findings related to the functions of miRNAs in breast cancer, which is the most frequent cancer in women, and discuss the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers

The Roles of MicroRNAs in Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Ryou-u [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Miyazaki, Hiroaki [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8555 (Japan); Ochiya, Takahiro, E-mail: tochiya@ncc.go.jp [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

2015-04-09

MicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide, non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. In various cancers, miRNAs play important roles in tumor initiation, drug resistance and metastasis. Recent studies reported that miRNAs could also be secreted via small endosome-derived vesicles called exosomes, which are derived from multiple cell types, including dendritic cells, lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to-cell communication and have been investigated as prognostic and diagnostic biomarkers. In this review, we summarize the major findings related to the functions of miRNAs in breast cancer, which is the most frequent cancer in women, and discuss the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers.

pulmonary tuberculosis, jimma hospital

African Journals Online (AJOL)

and National Tuberculosis and Leprosy Control Program manual. RESULTS: A total of 112 extra pulmonary ... Key words: Clinical audit; extra pulmonary Tuberculosis; National Tuberculosis and. Leprosy Control manual. "Addis Ababa ..... intern influence drug regimen selection. Compliance to the 1997 NTLCP inanual is.

Host immunity to Mycobacterium tuberculosis and risk of tuberculosis

DEFF Research Database (Denmark)

Michelsen, Sascha Wilk; Soborg, Bolette; Agger, Else-Marie

2016-01-01

BACKGROUND: Human immune responses to latent Mycobacterium tuberculosis (Mtb) infection (LTBI) may enable individuals to control Mtb infection and halt progression to tuberculosis (TB), a hypothesis applied in several novel TB vaccines. We aimed to evaluate whether immune responses to selected LTBI...

Detecting Ancient Tuberculosis

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Angela M. Gernaey

1998-12-01

Full Text Available Some diseases have played a more significant role in human development than others. Here we describe the results of a trial to diagnose ancient tuberculosis using chemical methods. Palaeo-epidemiological studies of the disease are compromised, but it has become apparent that tuberculosis (TB is a 'population-density dependent' disease. From modern studies, it is also apparent that the prevalence of TB can be used as an indicator of the level of poverty within the studied population. Mid-shaft rib samples from articulated individuals recovered from the former Newcastle Infirmary Burial Ground (1753-1845 AD were examined for mycolic acids that are species-specific for Mycobacterium tuberculosis. The 24% of ribs positive for mycolic acids correlated with the documented 27% tuberculosis prevalence. Mycolic acid biomarkers have the potential to provide an accurate trace of the palaeo-epidemiology of tuberculosis in ancient populations, thereby providing an indication of the overall level of poverty - a useful adjunct for archaeology.

Horizontal Transfer of Small RNAs To and From Plants

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Lu eHan

2015-12-01

Full Text Available Genetic information is traditionally thought to be transferred from parents to offspring. However, there is evidence indicating that gene transfer can also occur from microbes to higher species, such as plants, invertebrates and vertebrates. This horizontal transfer can be carried out by small RNAs (sRNAs. sRNAs have been recently reported to move across kingdoms as mobile signals, spreading silencing information toward targeted genes. sRNAs, especially microRNAs (miRNAs and small interfering RNAs (siRNAs, are non-coding molecules that control gene expression at the transcriptional or post-transcriptional level. Some sRNAs act in a cross-kingdom manner between animals and their parasites, but little is known about such sRNAs associated with plants. In this report, we provide a brief introduction to miRNAs that are transferred from plants to mammals/viruses and siRNAs that are transferred from microbes to plants. Both miRNAs and siRNAs can exert corresponding functions in the target organisms. Additionally, we provide information concerning a host-induced gene silencing (HIGS system as a potential application that utilizes the transgenic trafficking of RNA molecules to silence the genes of interacting organisms. Moreover, we lay out the controversial views regarding cross-kingdom miRNAs and call for better methodology and experimental design to confirm this unique function of miRNAs.

Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis

Directory of Open Access Journals (Sweden)

McGuire Abigail

2012-03-01

Full Text Available Abstract Background The sequence of the pathogen Mycobacterium tuberculosis (Mtb strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org, including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Results Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Conclusions Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

NARCIS (Netherlands)

Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C. Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J.; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R.; Sterling, Timothy R.; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J.; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K.; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-01-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health

MicroRNAs in Human Placental Development and Pregnancy Complications

Directory of Open Access Journals (Sweden)

Chun Peng

2013-03-01

Full Text Available MicroRNAs (miRNAs are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting that miRNAs play important roles during placental development. Aberrant miRNAs expression has been linked to pregnancy complications, such as preeclampsia. Recent research of placental miRNAs focuses on identifying placental miRNA species, examining differential expression of miRNAs between placentas from normal and compromised pregnancies, and uncovering the function of miRNAs in the placenta. More studies are required to further understand the functional significance of miRNAs in placental development and to explore the possibility of using miRNAs as biomarkers and therapeutic targets for pregnancy-related disorders. In this paper, we reviewed the current knowledge about the expression and function of miRNAs in placental development, and propose future directions for miRNA studies.

Tuberculosis neonatal

OpenAIRE

Pastor Durán, Xavier

1986-01-01

PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..

MicroRNAs: regulators of oncogenesis and stemness

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Papagiannakopoulos Thales

2008-06-01

Full Text Available Abstract MicroRNAs (miRNAs are essential post-transcriptional regulators that determine cell identity and fate. Aberrant expression of miRNAs can lead to diseases, including cancer. Expression of many miRNAs in the de-differentiated brain tumor cancer stem cells resembles that of neural stem cells. In this issue of BMC Medicine, Silber et al provide evidence of the expression of such miRNAs and their potential to mediate differentiation in both stem cell populations. In this commentary, we discuss the known functions of miRNAs in cancer and stem cells, their therapeutic potential and how the findings of Silber et al provide insight into the role of miR-124/miR-137 dysregulation in glioblastomas.

Diverse microRNAs with convergent functions regulate tumorigenesis.

Science.gov (United States)

Zhu, Min-Yan; Zhang, Wei; Yang, Tao

2016-02-01

MicroRNAs (miRNAs) regulate several biological processes, including tumorigenesis. In order to comprehend the roles of miRNAs in cancer, various screens were performed to investigate the changes in the expression levels of miRNAs that occur in different types of cancer. The present review focuses on the results of five recent screens, whereby a number of overlapping miRNAs were identified to be downregulated or differentially regulated, whereas no miRNAs were observed to be frequently upregulated. Furthermore, the majority of the miRNAs that were common to >1 screen were involved in signaling networks, including wingless-related integration site, receptor tyrosine kinase and transforming growth factor-β, or in cell cycle checkpoint control. The present review will discuss the aforementioned miRNAs implicated in cell cycle checkpoint control and signaling networks.

Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes*

Science.gov (United States)

Villota, Claudio; Campos, América; Vidaurre, Soledad; Oliveira-Cruz, Luciana; Boccardo, Enrique; Burzio, Verónica A.; Varas, Manuel; Villegas, Jaime; Villa, Luisa L.; Valenzuela, Pablo D. T.; Socías, Miguel; Roberts, Sally; Burzio, Luis O.

2012-01-01

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis. PMID:22539350

Expression of mitochondrial non-coding RNAs (ncRNAs) is modulated by high risk human papillomavirus (HPV) oncogenes.

Science.gov (United States)

Villota, Claudio; Campos, América; Vidaurre, Soledad; Oliveira-Cruz, Luciana; Boccardo, Enrique; Burzio, Verónica A; Varas, Manuel; Villegas, Jaime; Villa, Luisa L; Valenzuela, Pablo D T; Socías, Miguel; Roberts, Sally; Burzio, Luis O

2012-06-15

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.

MicroRNAs and toxicology: A love marriage

Directory of Open Access Journals (Sweden)

Elisabeth Schraml

Full Text Available With the dawn of personalized medicine, secreted microRNAs (miRNAs have come into the very focus of biomarker development for various diseases. MiRNAs fulfil key requirements of diagnostic tools such as i non or minimally invasive accessibility, ii robust, standardized and non-expensive quantitative analysis, iii rapid turnaround of the test result and iv most importantly because they provide a comprehensive snapshot of the ongoing physiologic processes in cells and tissues that package and release miRNAs into cell-free space. These characteristics have also established circulating miRNAs as promising biomarker candidates for toxicological studies, where they are used as biomarkers of drug-, or chemical-induced tissue injury for safety assessment. The tissue-specificity and early release of circulating miRNAs upon tissue injury, when damage is still reversible, are main factors for their clinical utility in toxicology. Here we summarize in brief, current knowledge of this field. Keywords: microRNAs, Biomarker, Toxicology, Minimal-invasive, DILI

Structural and Functional Motifs in Influenza Virus RNAs

Directory of Open Access Journals (Sweden)

Damien Ferhadian

2018-03-01

Full Text Available Influenza A viruses (IAV are responsible for recurrent influenza epidemics and occasional devastating pandemics in humans and animals. They belong to the Orthomyxoviridae family and their genome consists of eight (- sense viral RNA (vRNA segments of different lengths coding for at least 11 viral proteins. A heterotrimeric polymerase complex is bound to the promoter consisting of the 13 5′-terminal and 12 3′-terminal nucleotides of each vRNA, while internal parts of the vRNAs are associated with multiple copies of the viral nucleoprotein (NP, thus forming ribonucleoproteins (vRNP. Transcription and replication of vRNAs result in viral mRNAs (vmRNAs and complementary RNAs (cRNAs, respectively. Complementary RNAs are the exact positive copies of vRNAs; they also form ribonucleoproteins (cRNPs and are intermediate templates in the vRNA amplification process. On the contrary, vmRNAs have a 5′ cap snatched from cellular mRNAs and a 3′ polyA tail, both gained by the viral polymerase complex. Hence, unlike vRNAs and cRNAs, vmRNAs do not have a terminal promoter able to recruit the viral polymerase. Furthermore, synthesis of at least two viral proteins requires vmRNA splicing. Except for extensive analysis of the viral promoter structure and function and a few, mostly bioinformatics, studies addressing the vRNA and vmRNA structure, structural studies of the influenza A vRNAs, cRNAs, and vmRNAs are still in their infancy. The recent crystal structures of the influenza polymerase heterotrimeric complex drastically improved our understanding of the replication and transcription processes. The vRNA structure has been mainly studied in vitro using RNA probing, but its structure has been very recently studied within native vRNPs using crosslinking and RNA probing coupled to next generation RNA sequencing. Concerning vmRNAs, most studies focused on the segment M and NS splice sites and several structures initially predicted by bioinformatics analysis

The expanding universe of noncoding RNAs.

Science.gov (United States)

Hannon, G J; Rivas, F V; Murchison, E P; Steitz, J A

2006-01-01

The 71st Cold Spring Harbor Symposium on Quantitative Biology celebrated the numerous and expanding roles of regulatory RNAs in systems ranging from bacteria to mammals. It was clearly evident that noncoding RNAs are undergoing a renaissance, with reports of their involvement in nearly every cellular process. Previously known classes of longer noncoding RNAs were shown to function by every possible means-acting catalytically, sensing physiological states through adoption of complex secondary and tertiary structures, or using their primary sequences for recognition of target sites. The many recently discovered classes of small noncoding RNAs, generally less than 35 nucleotides in length, most often exert their effects by guiding regulatory complexes to targets via base-pairing. With the ability to analyze the RNA products of the genome in ever greater depth, it has become clear that the universe of noncoding RNAs may extend far beyond the boundaries we had previously imagined. Thus, as much as the Symposium highlighted exciting progress in the field, it also revealed how much farther we must go to understand fully the biological impact of noncoding RNAs.

MicroRNAs as a selective channel of communication between competing RNAs: a steady-state theory.

Science.gov (United States)

Figliuzzi, Matteo; Marinari, Enzo; De Martino, Andrea

2013-03-05

It has recently been suggested that the competition for a finite pool of microRNAs (miRNA) gives rise to effective interactions among their common targets (competing endogenous RNAs or ceRNAs) that could prove to be crucial for posttranscriptional regulation. We have studied a minimal model of posttranscriptional regulation where the emergence and the nature of such interactions can be characterized in detail at steady state. Sensitivity analysis shows that binding free energies and repression mechanisms are the key ingredients for the cross-talk between ceRNAs to arise. Interactions emerge in specific ranges of repression values, can be symmetrical (one ceRNA influences another and vice versa) or asymmetrical (one ceRNA influences another but not the reverse), and may be highly selective, while possibly limited by noise. In addition, we show that nontrivial correlations among ceRNAs can emerge in experimental readouts due to transcriptional fluctuations even in the absence of miRNA-mediated cross-talk. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Non-coding RNAs in the Ovarian Follicle

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Rosalia Battaglia

2017-05-01

Full Text Available The mammalian ovarian follicle is the complex reproductive unit comprising germ cell, somatic cells (Cumulus and Granulosa cells, and follicular fluid (FF: paracrine communication among the different cell types through FF ensures the development of a mature oocyte ready for fertilization. This paper is focused on non-coding RNAs in ovarian follicles and their predicted role in the pathways involved in oocyte growth and maturation. We determined the expression profiles of microRNAs in human oocytes and FF by high-throughput analysis and identified 267 microRNAs in FF and 176 in oocytes. Most of these were FF microRNAs, while 9 were oocyte specific. By bioinformatic analysis, independently performed on FF and oocyte microRNAs, we identified the most significant Biological Processes and the pathways regulated by their validated targets. We found many pathways shared between the two compartments and some specific for oocyte microRNAs. Moreover, we found 41 long non-coding RNAs able to interact with oocyte microRNAs and potentially involved in the regulation of folliculogenesis. These data are important in basic reproductive research and could also be useful for clinical applications. In fact, the characterization of non-coding RNAs in ovarian follicles could improve reproductive disease diagnosis, provide biomarkers of oocyte quality in Assisted Reproductive Treatment, and allow the development of therapies for infertility disorders.

Clinics of ocular tuberculosis.

Science.gov (United States)

Gupta, Vishali; Shoughy, Samir S; Mahajan, Sarakshi; Khairallah, Moncef; Rosenbaum, James T; Curi, Andre; Tabbara, Khalid F

2015-02-01

Ocular tuberculosis is an extrapulmonary tuberculous condition and has variable manifestations. The purpose of this review is to describe the clinical manifestations of ocular tuberculosis affecting the anterior and posterior segments of the eye in both immunocompetent and immunocompromised patients. Review of literature using Pubmed database. Mycobacterium tuberculosis may lead to formation of conjunctival granuloma, nodular scleritis, and interstitial keratitis. Lacrimal gland and orbital caseating granulomas are rare but may occur. The intraocular structures are also a target of insult by M. tuberculosis and may cause anterior granulomatous uveitis, anterior and posterior synechiae, secondary glaucoma, and cataract. The bacillus may involve the ciliary body, resulting in the formation of a localized caseating granuloma. Posterior segment manifestations include vitritis, retinal vasculitis, optic neuritis, serpiginous-like choroiditis, choroidal tubercules, subretinal neovascularization, and, rarely, endophthalmitis. The recognition of clinical signs of ocular tuberculosis is of utmost importance as it can provide clinical pathway toward tailored investigations and decision making for initiating anti-tuberculosis therapy.

Regulatory RNAs derived from transfer RNA?

Science.gov (United States)

Pederson, Thoru

2010-10-01

Four recent studies suggest that cleavages of transfer RNAs generate products with microRNA-like features, with some evidence of function. If their regulatory functions were to be confirmed, these newly revealed RNAs would add to the expanding repertoire of small noncoding RNAs and would also provide new perspectives on the coevolution of transfer RNA and messenger RNA.

MicroRNAs Expression Profiles in Cardiovascular Diseases

Directory of Open Access Journals (Sweden)

Elsa Bronze-da-Rocha

2014-01-01

Full Text Available The current search for new markers of cardiovascular diseases (CVDs is explained by the high morbidity and mortality still observed in developed and developing countries due to cardiovascular events. Recently, microRNAs (miRNAs or miRs have emerged as potential new biomarkers and are small sequences of RNAs that regulate gene expression at posttranscriptional level by inhibiting translation or inducing degradation of the target mRNAs. Circulating miRNAs are involved in the regulation of signaling pathways associated to aging and can be used as novel diagnostic markers for acute and chronic diseases such as cardiovascular pathologies. This review summarizes the biogenesis, maturation, and stability of miRNAs and their use as potential biomarkers for coronary artery disease (CAD, myocardial infarction (MI, and heart failure (HF.

Characterization of product RNAs synthesized in vitro by poliovirus RNA polymerase purified by chromatography on hydroxylapatite or poly(U) Sepharose.

OpenAIRE

Young, D C; Tobin, G J; Flanegan, J B

1987-01-01

The size of the product RNA synthesized by the poliovirus RNA polymerase and host factor was significantly affected by the type of column chromatography used to purify the polymerase. Dimer length product RNA was synthesized by the polymerase purified by chromatography on hydroxylapatite. This contrasted with the monomer length product RNA synthesized by the polymerase purified by chromatography on poly(U) Sepharose. The poly(U) Sepharose-purified polymerase was shown to contain oligo(U) that...

Imaging of musculoskeletal tuberculosis

International Nuclear Information System (INIS)

Boussel, L.; Marchand, B.; Blineau, N.; Picaud, G.; Emn, M.; Coulon, A.; Pagnon, P.; Rode, A.; Pin-Leveugle, J.; Berthezene, Y.; Pariset, C.; Boibieux, A.; Hermier, M.

2002-01-01

Purpose and methods. To perform an illustrated and educational review of musculoskeletal tuberculosis. Results. As the incidence of musculoskeletal tuberculosis still increases, a review appears justified. The following four main presentations are detailed and illustrated, by emphasizing the value of both CT and MR imaging: a) spine tuberculosis (∼ 50 %/) commonly involves two adjacent vertebral bodies with usual large paravertebral abscesses. The following lesions are highly suggestive of tuberculosis: solitary vertebral involvement, solitary epidural abscess with or without erosive spondylitis; b) osteo-arthritis: peripherally located erosions at synovial insertions with gradual narrowing of the joint space are highly suggestive; c) osteomyelitis: unusual, may involve any bones; d) tenosynovitis and bursitis. Conclusion. Imaging studies are essential for diagnosis and to assess the extent of musculo-skeletal tuberculosis. (author)

Imaging of pulmonary tuberculosis

International Nuclear Information System (INIS)

Van Dyck, P.; De Schepper, A.M.; Vanhoenacker, F.M.; Van den Brande, P.

2003-01-01

Tuberculosis, more than any other infectious disease, has always been a challenge, since it has been responsible for a great amount of morbidity and mortality in humans. After a steady decline in the number of new cases during the twentieth century, due to improved social and environmental conditions, early diagnosis, and the development of antituberculous medication, a stagnation and even an increase in the number of new cases was noted in the mid-1980s. The epidemiological alteration is multifactorial: global increase in developing countries; minority groups (HIV and other immunocompromised patients); and elderly patients due to an altered immune status. Other factors that may be responsible are a delayed diagnosis, especially in elderly patients, incomplete or inadequate therapy, and the emergence of multidrug-resistant tuberculosis. The course of the disease and its corresponding clinicoradiological pattern depends on the interaction between the organism and the host response. Classically, pulmonary tuberculosis has been classified in primary tuberculosis, which occurred previously in children, and postprimary tuberculosis, occurring in adult patients. In industrialized countries, however, there seems to be a shift of primary tuberculosis towards adults. Furthermore, due to an altered immunological response in certain groups, such as immunocompromised and elderly patients, an atypical radioclinical pattern may occur. The changing landscape, in which tuberculosis occurs, as well as the global resurgence, and the changed spectrum of the clinical and radiological presentation, justify a renewed interest of radiologists for the imaging features of pulmonary tuberculosis. This article deals with the usual imaging features of pulmonary tuberculosis as well as the atypical patterns encountered in immunodepressed and elderly patients. (orig.)

Primary prostatic tuberculosis: A rare form of genitourinary tuberculosis

African Journals Online (AJOL)

J.M. Ratkal

HOSTED BY. Pan African Urological Surgeons' Association. African Journal of Urology www.ees.elsevier.com/afju · www.sciencedirect.com. Case report. Primary prostatic tuberculosis: A rare form of genitourinary tuberculosis. J.M. Ratkal. KIMS, Hubli, India. Received 6 August 2014; received in revised form 28 August 2014 ...

microRNAs and lipid metabolism

Science.gov (United States)

Aryal, Binod; Singh, Abhishek K.; Rotllan, Noemi; Price, Nathan; Fernández-Hernando, Carlos

2017-01-01

Purpose of review Work over the last decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism. Recent findings A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the last two years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single nucleotide polymorphisms (SNP) in the proximity of miRNAs genes associated with abnormal levels of circulating lipids in humans. Several of these miRNA, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the low-density lipoprotein receptor (LDLR) and the ATP-binding cassette A1 (ABCA1). Summary microRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important non-coding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism. PMID:28333713

Tuberculosis in the lung (image)

Science.gov (United States)

Tuberculosis is caused by a group of organisms: Mycobacterium tuberculosis, M bovis , M africanum and a few other rarer subtypes. Tuberculosis usually appears as a lung (pulmonary) infection. However, ...

Patients with secondary amenorrhea due to tuberculosis endometritis towards the induced anti-tuberculosis drug category 1.

Science.gov (United States)

Perdhana, Raditya; Sutrisno, Sutrisno; Sugiri, Yani Jane; Baktiyani, Siti Candra Windu; Wiyasa, Arsana

2016-01-01

Tuberculosis (TB) is a disease which can affect various organs, including human's genital organs such as the endometrium. Tuberculosis endometritis can cause clinical symptoms of secondary amenorrhea and infertility. Infertility in genital TB caused by the involvement of the endometrium. The case presentation is 33-year-old woman from dr. Saiful Anwar Public Hospital to consult that she has not menstruated since 5 years ago (28 years old). The diagnosis was done by performing a clinical examination until the diagnosis of secondary amenorrhea due to tuberculosis endometritis is obtained. A treatment by using category I of anti-tuberculosis drugs was done for 6 months, afterward an Anatomical Pathology observation found no signs of the tuberculosis symptoms. Based on that, patient, who was diagnosed to have secondary amenorrhea due to tuberculosis endometritis, has no signs of tuberculosis process after being treated by using category I of anti-tuberculosis drugs for 6 months.

Improvement of the design and generation of highly specific plant knockdown lines using primary synthetic microRNAs (pri-smiRNAs

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Alves Leonardo

2010-03-01

Full Text Available Abstract Background microRNAs (miRNAs are endogenous small non-coding RNAs that post-transcriptionally regulate gene expression. In plants, they typically show high complementarity to a single sequence motif within their target mRNAs and act by catalyzing specific mRNA cleavage and degradation. miRNAs are processed from much longer primary transcripts via precursor miRNAs containing fold-back structures. Leaving these secondary structures intact, miRNAs can be re-designed experimentally to target mRNAs of choice. Results We designed primary synthetic miRNAs (pri-smiRNAs on the basis of the primary transcript of the Arabidopsis MIR159A gene by replacing the original miR159a and the corresponding miR159a* with novel sequences, keeping the overall secondary structure as predicted by the program RNAfold. We used the program RNAhybrid to optimize smiRNA design and to screen the complete Arabidopsis transcriptome for potential off-targets. To improve the molecular cloning of the pri-smiRNA we inserted restriction sites in the original MIR159A primary transcript to easily accommodate the smiRNA/smiRNA* DNA fragment. As a proof-of-concept, we targeted the single gene encoding chalcone synthase (CHS in Arabidopsis. We demonstrate smiRNA(CHS expression and CHS mRNA cleavage in different transgenic lines. Phenotypic changes in these lines were observed for seed color and flavonol derivatives, and quantified with respect to anthocyanin content. We also tested the effect of mismatches and excess G:U base pairs on knockdown efficiency. Conclusions RNAhybrid-assisted design of smiRNAs and generation of pri-smiRNAs using a novel vector containing restriction sites greatly improves specificity and speed of the generation of stable knockdown lines for functional analyses in plants.

MicroRNAs in right ventricular remodelling.

Science.gov (United States)

Batkai, Sandor; Bär, Christian; Thum, Thomas

2017-10-01

Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

International Nuclear Information System (INIS)

Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

1986-01-01

Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32 P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A + ) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A + ) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded

Radiology in silico-tuberculosis

International Nuclear Information System (INIS)

Otto, H.

1981-01-01

In spite of a decreasing number of new cases of silico-tuberculosis even today there still remains a serious complication of silicosis. The job of radiology is to recognise the disease, evaluate the course of the disease during therapy and classify the disease for compensation purposes. Due to the pathogenetic and pathomorphologic similarities of silicosis and tuberculosis, it is often difficult and sometimes even impossible to recognise the presence of tuberculosis in cases of silicoses or to identify and isolate the TB component in silico-tuberculosis. Careful consideration of all radiological and clinical parameters improves the accuracy of diagnosis. Since the radiographic examination provides the only method of evaluating the morphologic state of the disease, radiology will keep its central position in the diagnosis of silico-tuberculosis. (orig.) [de

The therapeutic potential of MicroRNAs in cancer

DEFF Research Database (Denmark)

Thorsen, Stine Buch; Obad, Susanna; Jensen, Niels Frank

2012-01-01

MicroRNAs (miRNAs) have been uncovered as important posttranscriptional regulators of nearly every biological process in the cell. Furthermore, mounting evidence implies that miRNAs play key roles in the pathogenesis of cancer and that many miRNAs can function either as oncogenes or tumor...

Abdominal tuberculosis in children

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Heda Melinda Nataprawira

2001-06-01

supported the diagnosis. There was no positive results of acid fast bacilli and culture done for Mycobacterium tuberculosis in gastric aspirate as well as ascitic fuid. Peritonitis tuberculosis was most commonly diagnosed (80.0%, followed by mesenterial/nodal tuberculosis (20.0%. All of the children followed (60.0% responded well to the drugs therapy.

Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation

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David Pires

2017-12-01

Full Text Available The success of tuberculosis (TB bacillus, Mycobacterium tuberculosis (Mtb, relies on the ability to survive in host cells and escape to immune surveillance and activation. We recently demonstrated that Mtb manipulation of host lysosomal cathepsins in macrophages leads to decreased enzymatic activity and pathogen survival. In addition, while searching for microRNAs (miRNAs involved in posttranscriptional gene regulation during mycobacteria infection of human macrophages, we found that selected miRNAs such as miR-106b-5p were specifically upregulated by pathogenic mycobacteria. Here, we show that miR-106b-5p is actively manipulated by Mtb to ensure its survival in macrophages. Using an in silico prediction approach, we identified miR-106b-5p with a potential binding to the 3′-untranslated region of cathepsin S (CtsS mRNA. We demonstrated by luminescence-based methods that miR-106b-5p indeed targets CTSS mRNA resulting in protein translation silencing. Moreover, miR-106b-5p gain-of-function experiments lead to a decreased CtsS expression favoring Mtb intracellular survival. By contrast, miR-106b-5p loss-of-function in infected cells was concomitant with increased CtsS expression, with significant intracellular killing of Mtb and T-cell activation. Modulation of miR-106b-5p did not impact necrosis, apoptosis or autophagy arguing that miR-106b-5p directly targeted CtsS expression as a way for Mtb to avoid exposure to degradative enzymes in the endocytic pathway. Altogether, our data suggest that manipulation of miR-106b-5p as a potential target for host-directed therapy for Mtb infection.

Rethinking the central dogma: noncoding RNAs are biologically relevant.

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Robinson, Victoria L

2009-01-01

Non-coding RNAs (ncRNAs) are a large class of functional molecules with over 100 unique classes described to date. ncRNAs are diverse in terms of their function and size. A relatively new class of small ncRNA, called microRNAs (miRNA), have received a great deal of attention in the literature in recent years. miRNAs are endogenously encoded gene families that demonstrate striking evolutionary conservation. miRNAs serve essential and diverse physiological functions such as differentiation and development, proliferation, maintaining cell type phenotypes, and many others. The discovery and ongoing investigation of miRNAs is part of a revolution in biology that is changing the basic concepts of gene expression and RNA functionality. A single miRNA can participate in controlling the expression of up to several hundred protein-coding genes by interacting with mRNAs, generally in 3' untranslated regions. Our new and developing understanding of miRNAs, and other ncRNAs, promises to lead to significant contributions to medicine. Specifically, miRNAs are likely to serve as the basis for novel therapies and diagnostic tools.

Limonia acidissima L. leaf mediated synthesis of zinc oxide nanoparticles: A potent tool against Mycobacterium tuberculosis.

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Taranath, Tarikere C; Patil, Bheemanagouda N

2016-06-01

The present investigation was undertaken to synthesize zinc oxide nanoparticles using Limonia acidissima L. and to test their efficacy against the growth of Mycobacterium tuberculosis. The formation of zinc oxide nanoparticles was confirmed with UV-visible spectrophotometry. Fourier transform infrared spectroscopy shows the presence of bio-molecules involved in the stabilization of zinc oxide nanoparticles. The shape and size was confirmed with atomic force microscope, X-ray diffraction, and high resolution transmission electron microscope. These nanoparticles were tested for their effect on the growth of M. tuberculosis through the microplate alamar blue assay technique. The UV-visible data reveal that an absorbance peak at 374nm confirms formation of zinc oxide nanoparticles and they are spherical in shape with sizes between 12nm and 53nm. These nanoparticles control the growth of M. tuberculosis at 12.5μg/mL. Phytosynthesis of zinc oxide nanoparticles is a green, eco-friendly technology because it is inexpensive and pollution free. In the present investigation, based on our results we conclude that the aqueous extract of leaves of L. acidissima can be used for the synthesis of zinc oxide nanoparticles. These nanoparticles control the growth of M. tuberculosis and this was confirmed with the microplate alamar blue method. The potential of biogenic zinc oxide nanoparticles may be harnessed as a novel medicine ingredient to combat tuberculosis disease. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Pulmonary tuberculosis

International Nuclear Information System (INIS)

Juhl, J.H.

1987-01-01

Dissemination of the tubercle bacillus is of three types: bronchogenic, hematogenous, and lymphangitic. Bronchogenic dissemination occurs when exudate from a cavity or small area of caseation drains into a bronchus and is aspirated into previously uninfected areas either on the same or on the opposite side. This type of spreading occurs frequently after bleeding and when there is a cavity emptying into a bronchus. Hematogenous dissemination leads to miliary tuberculosis and to extrapulmonary lesions throughout the body. Acute massive hematogenous spread causes miliary tuberculosis, while chronic spread in smaller amounts usually results in the chronic extrapulmonary foci. Lymphangitic dissemination is common in primary infection. It is responsible for involvement with subsequent enlargement of hilar and mediastinal nodes that is often seen in children and in young black adults. The reaction to M. tuberculosis depends on the presence or absence of immunity to tuberculoprotein. In individuals having no tissue hypersensitivity or immunity, primary tuberculosis results. In those with immunity produced by previous infection or BCG vaccination, the reactivation (reinfection) disease may develop

Circular RNAs as Promising Biomarkers: A mini-review

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Nadiah Abu

2016-08-01

Full Text Available The interest in circular RNAs has resurfaced in the past few years. What was considered as junk for nearly two decades is now one of the most interesting molecules. Circular RNAs are non-coding RNAs that are formed by back-splicing events and have covalently closed loops with no poly-adenylated tails. The regulation of circular RNAs is distinctive and they are selectively abundant in different types of tissues. Based on the current knowledge of circular RNAs, these molecules have the potential to be the next big thing especially as biomarkers for different diseases. This mini-review attempts to concisely look at the biology of circular RNAs, the putative functional activities, the prevalence of circular RNAs, and the possible role of circular RNA as biomarkers for diagnosis or measuring drug response.

CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

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Zahra Hasan

Full Text Available BACKGROUND: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. METHODOLOGY: We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB and healthy endemic controls (ECs, n = 36. TB patients comprised pulmonary (PTB, n = 34 and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16 or severe disseminated ETB (D-ETB, n = 16. Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined. RESULTS: M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01 as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023, while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005 patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04, while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036. TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02 and BCG (p = 0.03. Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups. CONCLUSIONS: The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.

The Potential of MicroRNAs as Prostate Cancer Biomarkers

NARCIS (Netherlands)

L. Fabris (Linda); Y. Ceder (Yvonne); A.M. Chinnaiyan (Arul); G.W. Jenster (Guido); K.D. Sorensen (Karina D.); S.A. Tomlins (Scott A); T. Visakorpi (Tapio); G.A. Calin (George)

2016-01-01

textabstractContext: Short noncoding RNAs known as microRNAs (miRNAs) control protein expression through the degradation of RNA or the inhibition of protein translation. The miRNAs influence a wide range of biologic processes and are often deregulated in cancer. This family of small RNAs constitutes

MicroRNAs Change the Landscape of Cancer Resistance.

Science.gov (United States)

Zhu, Jun; Zhu, Wei; Wu, Wei

2018-01-01

One of the major challenges in the cancer treatment is the development of drug resistance. It represents a major obstacle to curing cancer with constrained efficacy of both conventional chemotherapy and targeted therapies, even recent immune checkpoint blockade therapy. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in the resistance to various cancer treatments. MicroRNAs are a family of small noncoding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified in human genome. While one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance, thereby modulating the sensitivity of cancer cells to treatment. Therefore, manipulation of miRNAs may be an attractive strategy for more effective individualized therapies through reprograming resistant network in cancer cells.

Regulatory Role of Small Nucleolar RNAs in Human Diseases

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Grigory A. Stepanov

2015-01-01

Full Text Available Small nucleolar RNAs (snoRNAs are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs, namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

Tuberculosis Lymphoedema Cutis

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Gangopadhyay Asok Kumar

2001-01-01

Full Text Available Lymphoedema following cutaneous tuberculosis is a rare occurrence. A case of elephantiasis of leg following lupus vulgaris is presented. It can still be seen in rural India in untreated advanced cutaneous tuberculosis.

Distinct Spatiotemporal Dynamics of Peptidoglycan Synthesis between Mycobacterium smegmatis and Mycobacterium tuberculosis

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Helene Botella

2017-09-01

Full Text Available Peptidoglycan (PG, a polymer cross-linked by d-amino acid-containing peptides, is an essential component of the bacterial cell wall. We found that a fluorescent d-alanine analog (FDAA incorporates chiefly at one of the two poles in Mycobacterium smegmatis but that polar dominance varies as a function of the cell cycle in Mycobacterium tuberculosis: immediately after cytokinesis, FDAAs are incorporated chiefly at one of the two poles, but just before cytokinesis, FDAAs are incorporated comparably at both. These observations suggest that mycobacterial PG-synthesizing enzymes are localized in functional compartments at the poles and septum and that the capacity for PG synthesis matures at the new pole in M. tuberculosis. Deeper knowledge of the biology of mycobacterial PG synthesis may help in discovering drugs that disable previously unappreciated steps in the process.

MicroRNAs: A Puzzling Tool in Cancer Diagnostics and Therapy.

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D'Angelo, Barbara; Benedetti, Elisabetta; Cimini, Annamaria; Giordano, Antonio

2016-11-01

MicroRNAs (miRNAs) constitute a dominating class of small RNAs that regulate diverse cellular functions. Due the pivotal role of miRNAs in biological processes, a deregulated miRNA expression is likely involved in human cancers. MicroRNAs possess tumor suppressor capability, as well as display oncogenic characteristics. Interestingly, miRNAs exist in various biological fluids as circulating entities. Changes in the profile of circulating miRNAs are indicative of pathophysiological conditions in human cancer. This concept has led to consider circulating miRNAs valid biomarkers in cancer diagnostics. Furthermore, current research promotes the use of miRNAs as a target in cancer therapy. However, miRNAs are an evolving research field. Although miRNAs have been demonstrated to be potentially valuable tools both in cancer diagnosis and treatment, a greater effort should be made to improve our understanding of miRNAs biology. This review describes the biology of microRNAs, emphasizing on the use of miRNAs in cancer diagnostics and therapy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Primary isolated hepatic tuberculosis

International Nuclear Information System (INIS)

Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

2013-01-01

Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

Isolated Optic Disc Tuberculosis

Science.gov (United States)

Mansour, Ahmad M.; Tabbara, Khalid F.; Tabbarah, Zuhair

2015-01-01

We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation. PMID:26483675

Isolated Optic Disc Tuberculosis

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Ahmad M. Mansour

2015-09-01

Full Text Available We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation.

[Tuberculosis and HIV infection: experience of the national tuberculosis prevention program in Djibouti: 1990-1996].

Science.gov (United States)

Renoux, E; Matan, A Barreh; Sevre, J P; Mohamed Ali, I; Chami, D; Vincent, V

2002-01-01

Based on analysis of data collected from the national tuberculosis prevention program in Djibouti between 1990 and 1996, the authors analyzed the relationship between HIV infection and tuberculosis. The study cohort comprised a total of 22,000 patients including 14,000 with documented HIV infection. Although HIV infection probably worsened the situation, it was neither the only nor the main factor involved in the resurgence of tuberculosis. Demographic growth, higher population density, and increasing poverty as well as the quality of the national tuberculosis prevention program must be taken into account. The incidence of smear-negative tuberculosis was not significantly higher in HIV-infected patients (incidence of smear positive cases, > 92%). Extrapulmonary tuberculosis especially of pleural involvement was more common (15% versus 9.4%). Treatment was effective in HIV-infected patients. If directly observed (DOT) therapy was used, there was no risk of emergence of multidrug-resistant tuberculosis strains. Drug side-effects associated with the protocols used in Djibouti were not greater in HIV-infected patients. Most additional mortality observed in HIV-infected tuberculosis patients (10.5% versus 2%) was due to progression of HIV infection.

Characterization of piRNAs across postnatal development in mouse brain

KAUST Repository

Ghosheh, Yanal; Seridi, Loqmane; Ryu, Tae Woo; Takahashi, Hazuki; Orlando, Valerio; Carninci, Piero; Ravasi, Timothy

2016-01-01

PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues– where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.

Characterization of piRNAs across postnatal development in mouse brain

KAUST Repository

Ghosheh, Yanal

2016-04-26

PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues– where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.

Abdominal tuberculosis: Imaging features

International Nuclear Information System (INIS)

Pereira, Jose M.; Madureira, Antonio J.; Vieira, Alberto; Ramos, Isabel

2005-01-01

Radiological findings of abdominal tuberculosis can mimic those of many different diseases. A high level of suspicion is required, especially in high-risk population. In this article, we will describe barium studies, ultrasound (US) and computed tomography (CT) findings of abdominal tuberculosis (TB), with emphasis in the latest. We will illustrate CT findings that can help in the diagnosis of abdominal tuberculosis and describe imaging features that differentiate it from other inflammatory and neoplastic diseases, particularly lymphoma and Crohn's disease. As tuberculosis can affect any organ in the abdomen, emphasis is placed to ileocecal involvement, lymphadenopathy, peritonitis and solid organ disease (liver, spleen and pancreas). A positive culture or hystologic analysis of biopsy is still required in many patients for definitive diagnosis. Learning objectives:1.To review the relevant pathophysiology of abdominal tuberculosis. 2.Illustrate CT findings that can help in the diagnosis

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis

Institute of Scientific and Technical Information of China (English)

Yasushi Ihama; Akira Hokama; Kenji Hibiya; Kazuto Kishimoto; Manabu Nakamoto; Tetsuo Hirata; Nagisa Kinjo

2012-01-01

AIM:To investigate the utility of immunohistochemical (IHC) staining with an antibody to Mycobacterium tuberculosis (M.tuberculosis) for the diagnosis of intestinal tuberculosis (TB).METHODS:We retrospectively identified 10 patients (4 males and 6 females; mean age =65.1 ± 13.6 years)with intestinal TB.Clinical characteristics,including age,gender,underlying disease,and symptoms were obtained.Chest radiograph and laboratory tests,including sputum Ziehl-Neelsen (ZN) staining,M.tuberculosis culture,and sputum polymerase chain reaction (PCR)for tubercle bacilli DNA,as well as Tuberculin skin test (TST) and QuantiFERON-TB gold test (QFT),were examined.Colonoscopic records recorded on the basis of Sato's classification were also reviewed,in addition to data from intestinal biopsies examined for histopathological findings,including hematoxylin and eosin staining,and ZN staining,as well as M.tuberculosis culture,and PCR for tubercle bacilli DNA.For the present study,archived formalin-fixed paraffin-embedded (FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M.tuberculosis complex.These sections were also stained with the pan-macrophage marker CD68 antibody.RESULTS:From the clinical data,we found that no patients were immunocompromised,and that the main symptoms were diarrhea and weight loss.Three patients displayed active pulmonary TB,six patients (60％) had a positive TST,and 4 patients (40％) had a positive QFT.Colonoscopic findings revealed that all patients had type 1 findings (linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules),all of which were located in the right hemicolon and/or terminal ileum.Seven patients (70％) had concomitant healed lesions in the ileocecal area.No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples,and both M.tuberculosis

[Tuberculosis in compromised hosts].

Science.gov (United States)

2003-11-01

Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

Tuberculosis Facts - Exposure to TB

Science.gov (United States)

Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Tuberculosis Facts - Testing for TB

Science.gov (United States)

Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Tuberculosis and Diabetes

Science.gov (United States)

TUBERCULOSIS www.who.int/tb & DIABETES THE DUAL EPIDEMIC OF TB AND DIABETES DEADLY LINKAGES  People with ... higher risk of progressing from latent to active tuberculosis.  Diabetes triples a person’s risk of developing TB. ...

Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus

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Chaoqun Li

2018-01-01

Full Text Available Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice. Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to

Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus.

Science.gov (United States)

Li, Chaoqun; Cao, Feifei; Li, Shengli; Huang, Shenglin; Li, Wei; Abumaria, Nashat

2017-01-01

Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA) has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice). Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to stress

[Tuberculosis and drug-resistance tuberculosis in prisoners. Colombia, 2010-2012].

Science.gov (United States)

Gómez, Ingrid T; Llerena, Claudia R; Zabaleta, Angie P

2015-01-01

To characterize tuberculosis drug-resistance using anti-tuberculosis drug-sensitivity tests in Colombian prisoners. Descriptive-retrospective analyses were performed on cases of tuberculosis in prisoners. Samples were evaluated by the National Reference Laboratory. Conditions like gender, TB/VIH co-infection and drug-resistance were evaluated. Anti-tuberculosis drug-sensitivity tests were carried out on 72 prisoners. Results showed a distribution of 90.7 % of cases in males and 9.3 % of cases in females. 12 % of cases were TB/VIH co-infections, 94 % of the cases had not received any anti-tuberculosis treatment before, six isolates were drug-resistant corresponding to 8.8 % of total cases, and two cases were multi drug-resistant representing 1.3 % of the cases. Of the drug-resistant cases, 83.3 % were TB/VIH co-infected. Previously treated cases corresponded to 5.6 % of the total cases analyzed. One case with TB/VIH co-infection and rifampicin resistance was observed, representing 1.3 % of the total cases. The government must create a clear policy for prisoners in Colombia, because a high rate of disease in prisoners was observed. In addition, the results showed an association between drug-resistance and TB/VIH co-infection. Overcrowding and low quality of life in penitentiaries could become an important public health problem.

Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides

Science.gov (United States)

Nicolas, Francisco Esteban; Moxon, Simon; de Haro, Juan P.; Calo, Silvia; Grigoriev, Igor V.; Torres-Martínez, Santiago; Moulton, Vincent; Ruiz-Vázquez, Rosa M.; Dalmay, Tamas

2010-01-01

Endogenous short RNAs (esRNAs) play diverse roles in eukaryotes and usually are produced from double-stranded RNA (dsRNA) by Dicer. esRNAs are grouped into different classes based on biogenesis and function but not all classes are present in all three eukaryotic kingdoms. The esRNA register of fungi is poorly described compared to other eukaryotes and it is not clear what esRNA classes are present in this kingdom and whether they regulate the expression of protein coding genes. However, evidence that some dicer mutant fungi display altered phenotypes suggests that esRNAs play an important role in fungi. Here, we show that the basal fungus Mucor circinelloides produces new classes of esRNAs that map to exons and regulate the expression of many protein coding genes. The largest class of these exonic-siRNAs (ex-siRNAs) are generated by RNA-dependent RNA Polymerase 1 (RdRP1) and dicer-like 2 (DCL2) and target the mRNAs of protein coding genes from which they were produced. Our results expand the range of esRNAs in eukaryotes and reveal a new role for esRNAs in fungi. PMID:20427422

Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides

Energy Technology Data Exchange (ETDEWEB)

Grigoriev, Igor; Nicolas, Francisco; Moxon, Simon; Haro, Juan de; Calo, Silvia; Torres-Martinez, Santiago; Moulton, Vincent; Ruiz-Vazquez, Rosa; Dalmay, Tamas

2011-09-01

Endogenous short RNAs (esRNAs) play diverse roles in eukaryotes and usually are produced from double-stranded RNA (dsRNA) by Dicer. esRNAs are grouped into different classes based on biogenesis and function but not all classes are present in all three eukaryotic kingdoms. The esRNA register of fungi is poorly described compared to other eukaryotes and it is not clear what esRNA classes are present in this kingdom and whether they regulate the expression of protein coding genes. However, evidence that some dicer mutant fungi display altered phenotypes suggests that esRNAs play an important role in fungi. Here, we show that the basal fungus Mucor circinelloides produces new classes of esRNAs that map to exons and regulate the expression of many protein coding genes. The largest class of these exonic-siRNAs (ex-siRNAs) are generated by RNA-dependent RNA Polymerase 1 (RdRP1) and dicer-like 2 (DCL2) and target the mRNAs of protein coding genes from which they were produced. Our results expand the range of esRNAs in eukaryotes and reveal a new role for esRNAs in fungi

Development of an in situ hybridization assay for the detection of ostreid herpesvirus type 1 mRNAs in the Pacific oyster, Crassostrea gigas.

Science.gov (United States)

Corbeil, Serge; Faury, Nicole; Segarra, Amélie; Renault, Tristan

2015-01-01

An in situ hybridization protocol for detecting mRNAs of ostreid herpesvirus type 1 (OsHV-1) which infects Pacific oysters, Crassostrea gigas, was developed. Three RNA probes were synthesized by cloning three partial OsHV-1 genes into plasmids using three specific primer pairs, and performing a transcription in the presence of digoxigenin dUTP. The RNA probes were able to detect the virus mRNAs in paraffin sections of experimentally infected oysters 26 h post-injection. The in situ hybridization showed that the OsHV-1 mRNAs were mainly present in connective tissues in gills, mantle, adductor muscle, digestive gland and gonads. DNA detection by in situ hybridization using a DNA probe and viral DNA quantitation by real-time PCR were also performed and results were compared with those obtained using RNA probes. Copyright © 2014 Elsevier B.V. All rights reserved.

Exosomal miRNAs as biomarkers for prostate cancer

Directory of Open Access Journals (Sweden)

Nina Pettersen Hessvik

2013-03-01

Full Text Available miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids. Extracellular miRNAs exist in different forms - associated with Ago2 proteins, loaded into extracellular vesicles (exosomes, microvesicles or apoptotic bodies or into high density lipoprotein particles. These extracellular miRNAs are probably products of distinct cellular processes, and might therefore play different roles. However, their functions in vivo are currently unknown. In spite of this, they are considered as promising, noninvasive diagnostic and prognostic tools. Prostate cancer is the most common cancer in men in the Western world, but the currently used biomarker (prostate specific antigen has low specificity. Therefore, novel biomarkers are highly needed. In this review we will discuss possible biological functions of extracellular miRNAs, as well as the potential use of miRNAs from extracellular vesicles as biomarkers for prostate cancer.

Tuberculosis screening in patients with HIV

DEFF Research Database (Denmark)

Bjerrrum, Stephanie; Bonsu, Frank; Hanson-Nortey, Nii Nortey

2016-01-01

BACKGROUND: Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice...... is scarce. OBJECTIVES: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. DESIGN: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during...... May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations' guidelines...

Identification of Bacterial Small RNAs by RNA Sequencing

DEFF Research Database (Denmark)

Gómez Lozano, María; Marvig, Rasmus Lykke; Molin, Søren

2014-01-01

sequencing (RNA-seq) is described that involves the preparation and analysis of three different sequencing libraries. As a signifi cant number of unique sRNAs are identifi ed in each library, the libraries can be used either alone or in combination to increase the number of sRNAs identifi ed. The approach......Small regulatory RNAs (sRNAs) in bacteria are known to modulate gene expression and control a variety of processes including metabolic reactions, stress responses, and pathogenesis in response to environmental signals. A method to identify bacterial sRNAs on a genome-wide scale based on RNA...... may be applied to identify sRNAs in any bacterium under different growth and stress conditions....

Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells

International Nuclear Information System (INIS)

Su, Ming-Wei; Yu, Sung-Liang; Lin, Wen-Chang; Tsai, Ching-Hui; Chen, Po-Hua; Lee, Yungling Leo

2016-01-01

Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke. - Highlights: • We conducted a smoke reduction trial program and investigated the causal relationship between smoke and gene regulation. • MicroRNA and mRNA expression changes were examined in human PBMC. • MicroRNAs are important in regulating disease-causal genes after tobacco smoke reduction.

Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells

Energy Technology Data Exchange (ETDEWEB)

Su, Ming-Wei [Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Yu, Sung-Liang [Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Lin, Wen-Chang [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Tsai, Ching-Hui [Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Chen, Po-Hua [School of Medicine, National Taiwan University, Taipei, Taiwan (China); Lee, Yungling Leo, E-mail: leolee@ntu.edu.tw [Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China)

2016-08-15

Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke. - Highlights: • We conducted a smoke reduction trial program and investigated the causal relationship between smoke and gene regulation. • MicroRNA and mRNA expression changes were examined in human PBMC. • MicroRNAs are important in regulating disease-causal genes after tobacco smoke reduction.

Circulating mRNAs and miRNAs as candidate markers for the diagnosis and prognosis of prostate cancer

DEFF Research Database (Denmark)

Souza, Marilesia Ferreira de; Kuasne, Hellen; Barros-Filho, Mateus de Camargo

2017-01-01

Circulating nucleic acids are found in free form in body fluids and may serve as minimally invasive tools for cancer diagnosis and prognosis. Only a few studies have investigated the potential application of circulating mRNAs and microRNAs (miRNAs) in prostate cancer (PCa). The Cancer Genome Atlas......RNA expression revealed eleven genes and eight miRNAs which were validated by RT-qPCR in plasma samples from 102 untreated PCa patients and 50 cancer-free individuals. Two genes, OR51E2 and SIM2, and two miRNAs, miR-200c and miR-200b, showed significant association with PCa. Expression levels...... of these transcripts distinguished PCa patients from controls (67% sensitivity and 75% specificity). PCa patients and controls with prostate-specific antigen (PSA) ≤ 4.0 ng/mL were discriminated based on OR51E2 and SIM2 expression levels. The miR-200c expression showed association with Gleason score and miR-200b...

Dicer-independent processing of short hairpin RNAs

NARCIS (Netherlands)

Liu, Ying Poi; Schopman, Nick C. T.; Berkhout, Ben

2013-01-01

Short hairpin RNAs (shRNAs) are widely used to induce RNA interference (RNAi). We tested a variety of shRNAs that differed in stem length and terminal loop size and revealed strikingly different RNAi activities and shRNA-processing patterns. Interestingly, we identified a specific shRNA design that

Non-Coding RNAs in Arabidopsis

DEFF Research Database (Denmark)

van Wonterghem, Miranda

This work evolves around elucidating the mechanisms of micro RNAs (miRNAs) in Arabidopsis thaliana. I identified a new class of nuclear non-coding RNAs derived from protein coding genes. The genes are miRNA targets with extensive gene body methylation. The RNA species are nuclear localized and de...

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

Directory of Open Access Journals (Sweden)

Chan Zhou

2017-08-01

Full Text Available N6-methyladenosine (m6A is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ RNAs. We developed a computational pipeline (AutoCirc that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.

CT appearances of abdominal tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Lee, W.-K., E-mail: leewk33@hotmail.com [Department of Medical Imaging, St Vincent' s Hospital, University of Melbourne, Fitzroy, Victoria (Australia); Van Tonder, F.; Tartaglia, C.J.; Dagia, C. [Department of Medical Imaging, St Vincent' s Hospital, University of Melbourne, Fitzroy, Victoria (Australia); Cazzato, R.L. [Department of Radiology, Universita Campus Bio-Medico di Roma, Rome (Italy); Duddalwar, V.A. [Department of Radiology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California (United States); Chang, S.D. [Department of Medical Imaging, Vancouver General Hospital, University of British Columbia, British Columbia (Canada)

2012-06-15

The purpose of this article is to review and illustrate the spectrum of computed tomography (CT) appearances of abdominal tuberculosis. Tuberculosis can affect any organ or tissue in the abdomen, and can be mistaken for other inflammatory or neoplastic conditions. The most common sites of tuberculosis in the abdomen include lymph nodes, genitourinary tract, peritoneal cavity and gastrointestinal tract. The liver, spleen, biliary tract, pancreas and adrenals are rarely affected, but are more likely in HIV-seropositive patients and in miliary tuberculosis. This article should alert the radiologist to consider abdominal tuberculosis in the correct clinical setting to ensure timely diagnosis and enable appropriate treatment.

CT appearances of abdominal tuberculosis

International Nuclear Information System (INIS)

Lee, W.-K.; Van Tonder, F.; Tartaglia, C.J.; Dagia, C.; Cazzato, R.L.; Duddalwar, V.A.; Chang, S.D.

2012-01-01

The purpose of this article is to review and illustrate the spectrum of computed tomography (CT) appearances of abdominal tuberculosis. Tuberculosis can affect any organ or tissue in the abdomen, and can be mistaken for other inflammatory or neoplastic conditions. The most common sites of tuberculosis in the abdomen include lymph nodes, genitourinary tract, peritoneal cavity and gastrointestinal tract. The liver, spleen, biliary tract, pancreas and adrenals are rarely affected, but are more likely in HIV-seropositive patients and in miliary tuberculosis. This article should alert the radiologist to consider abdominal tuberculosis in the correct clinical setting to ensure timely diagnosis and enable appropriate treatment.

N6-adenosine methylation in MiRNAs.

Directory of Open Access Journals (Sweden)

Tea Berulava

Full Text Available Methylation of N6-adenosine (m6A has been observed in many different classes of RNA, but its prevalence in microRNAs (miRNAs has not yet been studied. Here we show that a knockdown of the m6A demethylase FTO affects the steady-state levels of several miRNAs. Moreover, RNA immunoprecipitation with an anti-m6A-antibody followed by RNA-seq revealed that a significant fraction of miRNAs contains m6A. By motif searches we have discovered consensus sequences discriminating between methylated and unmethylated miRNAs. The epigenetic modification of an epigenetic modifier as described here adds a new layer to the complexity of the posttranscriptional regulation of gene expression.

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.

Science.gov (United States)

Arvola, René M; Weidmann, Chase A; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2017-11-02

Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.

Identifying and annotating human bifunctional RNAs reveals their versatile functions.

Science.gov (United States)

Chen, Geng; Yang, Juan; Chen, Jiwei; Song, Yunjie; Cao, Ruifang; Shi, Tieliu; Shi, Leming

2016-10-01

Bifunctional RNAs that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional RNAs by integrating tandem mass spectrometry and RNA-seq data. We first constructed a pipeline to identify and annotate bifunctional RNAs, leading to the characterization of 132 high-confidence bifunctional RNAs. Our analyses indicate that bifunctional RNAs may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional RNAs could interact with multiple miRNAs and RNA-binding proteins to exert their corresponding roles. Bifunctional RNAs may also function as competing endogenous RNAs to regulate the expression of many genes by competing for common targeting miRNAs. Finally, somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional RNAs. Collectively, our study not only provides the pipeline for identifying and annotating bifunctional RNAs but also reveals their important gene-regulatory functions.

Diversity of small RNAs expressed in Pseudomonas species

DEFF Research Database (Denmark)

Gomez-Lozano, Mara; Marvig, Rasmus Lykke; Molina-Santiago, Carlos

2015-01-01

RNA sequencing (RNA-seq) has revealed several hundreds of previously undetected small RNAs (sRNAs) in all bacterial species investigated, including strains of Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas syringae. Nonetheless, only little is known about the extent of conservation...... of expressed sRNAs across strains and species. In this study, we have used RNA-seq to identify sRNAs in P.putidaDOT-T1E and Pseudomonas extremaustralis 14-3b. This is the first strain of P.extremaustralis and the second strain of P.putida to have their transcriptomes analysed for sRNAs, and we identify...... the presence of around 150 novel sRNAs in each strain. Furthermore, we provide a comparison based on sequence conservation of all the sRNAs detected by RNA-seq in the Pseudomonas species investigated so far. Our results show that the extent of sRNA conservation across different species is very limited...

Ocular tuberculosis: current perspectives

Directory of Open Access Journals (Sweden)

Shakarchi FI

2015-11-01

Full Text Available Faiz I Shakarchi1,21Ibn Al-Haetham Teaching Eye Hospital, 2Department of Opthalmology, Medical College, Al-Mustansiriya University, Baghdad, IraqAbstract: The World Health Organization currently estimates that nearly two billion people, or one-third of the world’s population, are infected by tuberculosis, and that roughly 10% of the infected people are symptomatic. Tuberculosis affects the lungs in 80% of patients, while in the remaining 20% the disease may affect other organs, including the eye. Uveitis can be seen concurrently with tuberculosis, but a direct association is difficult to prove. Ocular tuberculosis is usually not associated with clinical evidence of pulmonary tuberculosis, as up to 60% of extrapulmonary tuberculosis patients may not have pulmonary disease. The diagnosis of tuberculous uveitis is often problematic and in nearly all reported cases, the diagnosis was only presumptive. Tuberculous uveitis is a great mimicker of various uveitis entities and it can be considered in the differential diagnosis of any type of intraocular inflammation. It is still unknown if ocular manifestations result from a direct mycobacterium infection or hypersensitivity reaction and this is reflected on the management of tuberculous uveitis. Prevalence of tuberculosis as an etiology of uveitis may reach up to 10% in endemic areas. Tuberculous uveitis is a vision-threatening disease that inevitably leads to blindness if not properly diagnosed and treated. The aim of this review is to illustrate the various clinical features and management of presumed tuberculous uveitis. The current review focuses on the diagnostic criteria, significance of tuberculin skin test, and use of systemic corticosteroids in the management of tuberculous uveitis as recommended in recent publications.Keywords: tuberculosis, uveitis, choroiditis, tuberculin skin test

Perinatal tuberculosis: a diagnostic challenge

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Edna Lúcia S. de Souza

Full Text Available Despite the high prevalence of tuberculosis in adults and children, the congenital and perinatal forms of tuberculosis are rare. In Brazil, there has been only one published case of congenital tuberculosis and two cases of the perinatal form of this disease. We report a case of perinatal tuberculosis presenting with pneumonia. Alcohol-acid-resistant bacilli were found in the gastric lavage. Diagnosis of this disease presentation requires a high index of suspicion.

Abdominal tuberculosis: Imaging features

Energy Technology Data Exchange (ETDEWEB)

Pereira, Jose M. [Department of Radiology, Hospital de S. Joao, Porto (Portugal)]. E-mail: jmpjesus@yahoo.com; Madureira, Antonio J. [Department of Radiology, Hospital de S. Joao, Porto (Portugal); Vieira, Alberto [Department of Radiology, Hospital de S. Joao, Porto (Portugal); Ramos, Isabel [Department of Radiology, Hospital de S. Joao, Porto (Portugal)

2005-08-01

Radiological findings of abdominal tuberculosis can mimic those of many different diseases. A high level of suspicion is required, especially in high-risk population. In this article, we will describe barium studies, ultrasound (US) and computed tomography (CT) findings of abdominal tuberculosis (TB), with emphasis in the latest. We will illustrate CT findings that can help in the diagnosis of abdominal tuberculosis and describe imaging features that differentiate it from other inflammatory and neoplastic diseases, particularly lymphoma and Crohn's disease. As tuberculosis can affect any organ in the abdomen, emphasis is placed to ileocecal involvement, lymphadenopathy, peritonitis and solid organ disease (liver, spleen and pancreas). A positive culture or hystologic analysis of biopsy is still required in many patients for definitive diagnosis. Learning objectives:1.To review the relevant pathophysiology of abdominal tuberculosis. 2.Illustrate CT findings that can help in the diagnosis.

Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients

DEFF Research Database (Denmark)

Doherty, T Mark; Demissie, Abebech; Olobo, Joseph

2002-01-01

Diagnosis of latent Mycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients...... correlates with the subsequent development of active tuberculosis during a 2-year follow-up period....

Espectro clínico de tuberculosis cutánea Clinic spectrum of cutaneous tuberculosis

OpenAIRE

G Pizzariello; P Fernández Pardal; G D´Atri; V Novac; A Uranga

2008-01-01

La Tuberculosis (TBC) es producida por el Mycobacterium tuberculosis o bacilo de Koch, y se ha observado en las últimas décadas, una reemergencia de casos pulmonares y extrapulmonares. La TBC cutánea es infrecuente, y presenta un amplio espectro clínico dependiendo del interjuego existente entre el agente, el huésped y el ambiente. TBC cutánea, ilustrándola con casos clínicos de pacientes que concurrieron a nuestro servicio.Tuberculosis (TBC) is caused by Mycobacterium tuberculosis or Koch's ...

Mammalian small nucleolar RNAs are mobile genetic elements.

Directory of Open Access Journals (Sweden)

Michel J Weber

2006-12-01

Full Text Available Small nucleolar RNAs (snoRNAs of the H/ACA box and C/D box categories guide the pseudouridylation and the 2'-O-ribose methylation of ribosomal RNAs by forming short duplexes with their target. Similarly, small Cajal body-specific RNAs (scaRNAs guide modifications of spliceosomal RNAs. The vast majority of vertebrate sno/scaRNAs are located in introns of genes transcribed by RNA polymerase II and processed by exonucleolytic trimming after splicing. A bioinformatic search for orthologues of human sno/scaRNAs in sequenced mammalian genomes reveals the presence of species- or lineage-specific sno/scaRNA retroposons (sno/scaRTs characterized by an A-rich tail and an approximately 14-bp target site duplication that corresponds to their insertion site, as determined by interspecific genomic alignments. Three classes of snoRTs are defined based on the extent of intron and exon sequences from the snoRNA parental host gene they contain. SnoRTs frequently insert in gene introns in the sense orientation at genomic hot spots shared with other genetic mobile elements. Previously characterized human snoRNAs are encoded in retroposons whose parental copies can be identified by phylogenic analysis, showing that snoRTs can be faithfully processed. These results identify snoRNAs as a new family of mobile genetic elements. The insertion of new snoRNA copies might constitute a safeguard mechanism by which the biological activity of snoRNAs is maintained in spite of the risk of mutations in the parental copy. I furthermore propose that retroposition followed by genetic drift is a mechanism that increased snoRNA diversity during vertebrate evolution to eventually acquire new RNA-modification functions.

TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL

Science.gov (United States)

Mendoza-Ticona, Alberto

2014-01-01

Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto. PMID:22858771

Temporal analysis of reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012

Directory of Open Access Journals (Sweden)

Renato Simões Gaspar

Full Text Available ABSTRACT Objective: To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. Methods: This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Results: Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Conclusions: Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished.

Trash or Treasure: extracellular microRNAs and cell-to-cell communication

Directory of Open Access Journals (Sweden)

Nobuyoshi eKosaka

2013-09-01

Full Text Available Circulating RNAs in human body fluids are promising candidates for diagnostic purposes. However, the biological significance of circulating RNAs remains elusive. Recently, small non-coding RNAs, microRNAs (miRNAs, were isolated from multiple human body fluids, and these circulating miRNAs have been implicated as novel disease biomarkers. Concurrently, miRNAs were also identified in the extracellular space associated with extracellular vesicles (EVs, which are small membrane vesicles secreted from various types of cells. The function of these secreted miRNAs has been revealed in several papers. Circulating miRNAs have been experimentally found to be associated with EVs, however, other types of extracellular miRNAs were also described. This review discusses studies related to extracellular miRNAs, including circulating miRNAs and secreted miRNAs, to highlight the importance of studying not only secreted miRNAs but also circulating miRNAs to determine the contribution of extracellular miRNAs especially in cancer development.

Structured RNAs and synteny regions in the pig genome

DEFF Research Database (Denmark)

Anthon, Christian; Tafer, Hakim; Havgaard, Jakob H

2014-01-01

BACKGROUND: Annotating mammalian genomes for noncoding RNAs (ncRNAs) is nontrivial since far from all ncRNAs are known and the computational models are resource demanding. Currently, the human genome holds the best mammalian ncRNA annotation, a result of numerous efforts by several groups. However......, a more direct strategy is desired for the increasing number of sequenced mammalian genomes of which some, such as the pig, are relevant as disease models and production animals. RESULTS: We present a comprehensive annotation of structured RNAs in the pig genome. Combining sequence and structure...... lncRNA loci, 11 conflicts of annotation, and 3,183 ncRNA genes. The ncRNA genes comprise 359 miRNAs, 8 ribozymes, 185 rRNAs, 638 snoRNAs, 1,030 snRNAs, 810 tRNAs and 153 ncRNA genes not belonging to the here fore mentioned classes. When running the pipeline on a local shuffled version of the genome...

Identifying MicroRNAs and Transcript Targets in Jatropha Seeds

Science.gov (United States)

Galli, Vanessa; Guzman, Frank; de Oliveira, Luiz F. V.; Loss-Morais, Guilherme; Körbes, Ana P.; Silva, Sérgio D. A.; Margis-Pinheiro, Márcia M. A. N.; Margis, Rogério

2014-01-01

MicroRNAs, or miRNAs, are endogenously encoded small RNAs that play a key role in diverse plant biological processes. Jatropha curcas L. has received significant attention as a potential oilseed crop for the production of renewable oil. Here, a sRNA library of mature seeds and three mRNA libraries from three different seed development stages were generated by deep sequencing to identify and characterize the miRNAs and pre-miRNAs of J. curcas. Computational analysis was used for the identification of 180 conserved miRNAs and 41 precursors (pre-miRNAs) as well as 16 novel pre-miRNAs. The predicted miRNA target genes are involved in a broad range of physiological functions, including cellular structure, nuclear function, translation, transport, hormone synthesis, defense, and lipid metabolism. Some pre-miRNA and miRNA targets vary in abundance between the three stages of seed development. A search for sequences that produce siRNA was performed, and the results indicated that J. curcas siRNAs play a role in nuclear functions, transport, catalytic processes and disease resistance. This study presents the first large scale identification of J. curcas miRNAs and their targets in mature seeds based on deep sequencing, and it contributes to a functional understanding of these miRNAs. PMID:24551031

Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis*

Science.gov (United States)

Rahman, Md. Aejazur; Sobia, Parveen; Dwivedi, Ved Prakash; Bhawsar, Aakansha; Singh, Dhiraj Kumar; Sharma, Pawan; Moodley, Prashini; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

2015-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence. PMID:25847237

Targeting phenotypically tolerant Mycobacterium tuberculosis

Science.gov (United States)

Gold, Ben; Nathan, Carl

2016-01-01

While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

Bovine Tuberculosis, A Zoonotic Disease

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Tarmudji

2008-12-01

Full Text Available Bovine tuberculosis is caused by the infection of Mycobacterium tuberculosis var. bovis (M. bovis. This species is one of Mycobacterium tuberculosis complex, can infect wide range of hosts: cattle and other domesticated animals, wild mammals and humans (zoonotic. M. bovis bacterium from infected hosts can be transmitted to other susceptible animals and humans through respiratory excretes and secretion materials. Humans can be infected with M. bovis by ingested M. bovis contaminated animal products, unpasteurised milk from tuberculosis cows or through respiratory route of contaminated aerosol. Bovine tuberculosis at the first stage does not show any clinical sign but as the disease progress in the next stage which may take several months or years, clinical signs may arise, suh as: fluctuative body temperature, anorexia, lost body weight, coughing, oedema of lymph nodes, increased respiratory frequencies. Pathological lesion of bovine tuberculosis is characterised by the formation of granulomas (tubercles, in which bacterial cells have been localised, most in lymph nodes and pulmonum, but can occur in other organs. The granulomas usually arise in small nodules or tubercles appear yellowish either caseus, caseo-calcareus or calcified. In Indonesia, bovine tuberculosis occurred in dairy cattle since 1905 through the imported dairy cows from Holland and Australian. It was unfortunate that until recently, there were not many research and surveilances of bovine tuberculosis conducted in this country, so the distribution of bovine tuberculosis is unknown. Early serological diagnosis can be done on live cattle by means of tuberculin tests under field conditions. Confirmation can be done by isolation and identification of excreted and secreted samples from the slaughter house. Antibiotic treatment and vaccination were uneffective, therefore the effective control of bovine tuberculosis is suggested by tuberculin tests and by slaughtering the selected

[Current tuberculosis mortality world-wide].

Science.gov (United States)

Haefliger, E; Rieder, H L

1992-04-21

The mortality rate still is an important index for assessment of tuberculosis. Statistical records are kept on the mortality rate on a worldwide basis--more than in the case of other tuberculosis parameters. They allow us to make valuable comparisons. They are also useful because the mortality is closely related to the morbidity. The present thesis is based on comparative figures from the 1989 volume of the WHO Health Statistics Annual. Various countries have been specially selected by the publisher--and subsequently also by us--for sake of clarity. The figures vary strongly within these countries, which was to be expected. The mortality rate varies in Europe (for each 100,000 residents) e.g. from 0.2 in the Netherlands to 8.15 in the Soviet Union. In the Americas the rates vary from 0.4 for Canada to 12.9 for Ecuador. In the Western Pacific region the mortality rates vary from 0.35 for Australia to 14.65 for China. On a worldwide basis, the share of deaths from tuberculosis among all causes of death varies from 0.02% in the Netherlands to 2.10% in the Republic of Korea. The relation of tuberculosis deaths with regard to sexes in Switzerland: 75.7% men, 24.3% women, which is more or less the European average. The lower the mortality rate for tuberculosis are, the lower the difference between the sexes appears to be. Similar facts are found with regard to the distribution of tuberculosis deaths according to age groups: the lower the tuberculosis rate, the more tuberculosis is found in older age groups. The tuberculosis deaths are percentage-wise similarly distributed to the respiratory organs and the other tuberculosis forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

DEFF Research Database (Denmark)

Pauli, Andrea; Valen, Eivind; Lin, Michael F.

2012-01-01

Long non-coding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in human and mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during...... of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression...... and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms...

MicroRNAs, epigenetics and disease

DEFF Research Database (Denmark)

Silahtaroglu, Asli; Stenvang, Jan

2010-01-01

Epigenetics is defined as the heritable chances that affect gene expression without changing the DNA sequence. Epigenetic regulation of gene expression can be through different mechanisms such as DNA methylation, histone modifications and nucleosome positioning. MicroRNAs are short RNA molecules...... which do not code for a protein but have a role in post-transcriptional silencing of multiple target genes by binding to their 3' UTRs (untranslated regions). Both epigenetic mechanisms, such as DNA methylation and histone modifications, and the microRNAs are crucial for normal differentiation...... diseases. In the present chapter we will mainly focus on microRNAs and methylation and their implications in human disease, mainly in cancer....

Mycobacterium tuberculosis Metabolism

Science.gov (United States)

Warner, Digby F.

2015-01-01

Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

Detection and Analysis of Circular RNAs by RT-PCR.

Science.gov (United States)

Panda, Amaresh C; Gorospe, Myriam

2018-03-20

Gene expression in eukaryotic cells is tightly regulated at the transcriptional and posttranscriptional levels. Posttranscriptional processes, including pre-mRNA splicing, mRNA export, mRNA turnover, and mRNA translation, are controlled by RNA-binding proteins (RBPs) and noncoding (nc)RNAs. The vast family of ncRNAs comprises diverse regulatory RNAs, such as microRNAs and long noncoding (lnc)RNAs, but also the poorly explored class of circular (circ)RNAs. Although first discovered more than three decades ago by electron microscopy, only the advent of high-throughput RNA-sequencing (RNA-seq) and the development of innovative bioinformatic pipelines have begun to allow the systematic identification of circRNAs (Szabo and Salzman, 2016; Panda et al ., 2017b; Panda et al ., 2017c). However, the validation of true circRNAs identified by RNA sequencing requires other molecular biology techniques including reverse transcription (RT) followed by conventional or quantitative (q) polymerase chain reaction (PCR), and Northern blot analysis (Jeck and Sharpless, 2014). RT-qPCR analysis of circular RNAs using divergent primers has been widely used for the detection, validation, and sometimes quantification of circRNAs (Abdelmohsen et al ., 2015 and 2017; Panda et al ., 2017b). As detailed here, divergent primers designed to span the circRNA backsplice junction sequence can specifically amplify the circRNAs and not the counterpart linear RNA. In sum, RT-PCR analysis using divergent primers allows direct detection and quantification of circRNAs.

microRNAs in CNS disorders

DEFF Research Database (Denmark)

Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes

2009-01-01

RNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...

9 CFR 381.81 - Tuberculosis.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

Interfering Satellite RNAs of Bamboo mosaic virus

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Kuan-Yu Lin

2017-05-01

Full Text Available Satellite RNAs (satRNAs are sub-viral agents that may interact with their cognate helper virus (HV and host plant synergistically and/or antagonistically. SatRNAs totally depend on the HV for replication, so satRNAs and HV usually evolve similar secondary or tertiary RNA structures that are recognized by a replication complex, although satRNAs and HV do not share an appreciable sequence homology. The satRNAs of Bamboo mosaic virus (satBaMV, the only satRNAs of the genus Potexvirus, have become one of the models of how satRNAs can modulate HV replication and virus-induced symptoms. In this review, we summarize the molecular mechanisms underlying the interaction of interfering satBaMV and BaMV. Like other satRNAs, satBaMV mimics the secondary structures of 5′- and 3′-untranslated regions (UTRs of BaMV as a molecular pretender. However, a conserved apical hairpin stem loop (AHSL in the 5′-UTR of satBaMV was found as the key determinant for downregulating BaMV replication. In particular, two unique nucleotides (C60 and C83 in the AHSL of satBaMVs determine the satBaMV interference ability by competing for the replication machinery. Thus, transgenic plants expressing interfering satBaMV could confer resistance to BaMV, and interfering satBaMV could be used as biological-control agent. Unlike two major anti-viral mechanisms, RNA silencing and salicylic acid-mediated immunity, our findings in plants by in vivo competition assay and RNA deep sequencing suggested replication competition is involved in this transgenic satBaMV-mediated BaMV interference. We propose how a single nucleotide of satBaMV can make a great change in BaMV pathogenicity and the underlying mechanism.

Tuberculosis screening in patients with HIV

DEFF Research Database (Denmark)

Bjerrum, Stephanie Mia Katrine; Bonsu, Frank; Hanson-Nortey, Nii Nortey

2016-01-01

BACKGROUND: Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice...... is scarce. OBJECTIVES: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. DESIGN: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during...

Ultrasonographic and CT findings of hepatosplenic tuberculosis

International Nuclear Information System (INIS)

Moon, Un Hyeon; Lee, Jeong Seok; Ko, Kang Seok; Park, Byung Ran; Yang, Dong Cheol; Im, Ju Hyeon; Kang, In Young

1998-01-01

To evaluate the ultrasonographic and CT findings of hepatosplenic tuberculosis Materials and Methods: We retrospectively reviewed the ultrasonographic and CT findings of confirmed hepatosplenic tuberculosis in 12 patients. Six were men and six were women ; their average age was 41, and most were in their twenties. Lesions of the liver and spleen, as well as associated findings such as abdominal tuberculosis and other organ involvement of tuberculosis were analyzed. Results : There were three cases of hepatic tuberculosis, seven of splenic tuberculosis, and two of hepatosplenic involvement of tuberculosis. On the basis of the ultrasonographic and CT findings, hepatosplenic tuberculosis was classified as one of two patterns : miliary or micronodular, ormacronodular. The micronodular type was more common (9/12 cases) being characterized by innumerable micronodules,and with easy coalescence in the liver and spleen in five of the nine cases. The macronodular type of low density mass was noted in the other three patients. Splenomegaly was noted in 12 cases and hepatomegaly in ten. Pulmonary tuberculosis-including the miliary type(n=5)-was noted in eight patients. Associated abdominal tuberculosis such as lymphadenopathy with central low density and peripheral rim enhancement (n=6), tuberculous peritonitis(n=3),highly attenuated ascites(n=6), adrenal tuberculosis(n=1), renal tuberculosis(n=1), ovarian abscess(n=1), psoasabscess(n=1), and systemic tuberculosis such as central nervous system tuberculoma(n=2), cervical lymphadenopathy(n=4) and tuberculous spondylitis(n=1) were noted. Conclusion : Ultrasonography and CT were valuable in the detection and diagnosis of hepatosplenic tuberculosis

Ultrasonographic and CT findings of hepatosplenic tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Moon, Un Hyeon; Lee, Jeong Seok; Ko, Kang Seok; Park, Byung Ran; Yang, Dong Cheol; Im, Ju Hyeon [Kwangju Christian Hospital, Kwangju (Korea, Republic of); Kang, In Young [Kwangju Green Cross Hospital, Kwangju (Korea, Republic of)

1998-08-01

To evaluate the ultrasonographic and CT findings of hepatosplenic tuberculosis Materials and Methods: We retrospectively reviewed the ultrasonographic and CT findings of confirmed hepatosplenic tuberculosis in 12 patients. Six were men and six were women ; their average age was 41, and most were in their twenties. Lesions of the liver and spleen, as well as associated findings such as abdominal tuberculosis and other organ involvement of tuberculosis were analyzed. Results : There were three cases of hepatic tuberculosis, seven of splenic tuberculosis, and two of hepatosplenic involvement of tuberculosis. On the basis of the ultrasonographic and CT findings, hepatosplenic tuberculosis was classified as one of two patterns : miliary or micronodular, ormacronodular. The micronodular type was more common (9/12 cases) being characterized by innumerable micronodules,and with easy coalescence in the liver and spleen in five of the nine cases. The macronodular type of low density mass was noted in the other three patients. Splenomegaly was noted in 12 cases and hepatomegaly in ten. Pulmonary tuberculosis-including the miliary type(n=5)-was noted in eight patients. Associated abdominal tuberculosis such as lymphadenopathy with central low density and peripheral rim enhancement (n=6), tuberculous peritonitis(n=3),highly attenuated ascites(n=6), adrenal tuberculosis(n=1), renal tuberculosis(n=1), ovarian abscess(n=1), psoasabscess(n=1), and systemic tuberculosis such as central nervous system tuberculoma(n=2), cervical lymphadenopathy(n=4) and tuberculous spondylitis(n=1) were noted. Conclusion : Ultrasonography and CT were valuable in the detection and diagnosis of hepatosplenic tuberculosis.

Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.

Directory of Open Access Journals (Sweden)

Ilona Patursky-Polischuk

Full Text Available TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation.

Circular RNAs: Biogenesis, Function and Role in Human Diseases

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John Greene

2017-06-01

Full Text Available Circular RNAs (circRNAs are currently classed as non-coding RNA (ncRNA that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3′ and 5′ ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization. Interestingly, they have been found to be abundant, evolutionally conserved and relatively stable in the cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription. It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression. circRNAs appear to be more often downregulated in tumor tissue compared to normal tissue and this may be due to (i errors in the back-splice machinery in malignant tissues, (ii degradation of circRNAs by deregulated miRNAs in tumor tissue, or (iii increasing cell proliferation leading to a reduction of circRNAs. circRNAs have been identified in exosomes and more recently, chromosomal translocations in cancer have been shown to generate aberrant fusion-circRNAs associated with resistance to drug treatments. In addition, though originally thought to be non-coding, there is now increasing evidence to suggest that select circRNAs can be translated into functional proteins. Although much remains to be elucidated about circRNA biology and mechanisms of gene regulation, these ncRNAs are quickly emerging as

Pictorial essay: Orbital tuberculosis

International Nuclear Information System (INIS)

Narula, Mahender K; Chaudhary, Vikas; Baruah, Dhiraj; Kathuria, Manoj; Anand, Rama

2010-01-01

Tuberculosis of the orbit is rare, even in places where tuberculosis is endemic. The disease may involve soft tissue, the lacrimal gland, or the periosteum or bones of the orbital wall. Intracranial extension, in the form of extradural abscess, and infratemporal fossa extension has been described. This pictorial essay illustrates the imaging findings of nine histopathologically confirmed cases of orbital tuberculosis. All these patients responded to antituberculous treatment

Association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area

NARCIS (Netherlands)

den Boon, S.; van Lill, S. W. P.; Borgdorff, M. W.; Verver, S.; Bateman, E. D.; Lombard, C. J.; Enarson, D. A.; Beyers, N.

2005-01-01

Background: Associations between smoking and tuberculosis disease including death from tuberculosis have been reported, but there are few reports on the influence of smoking on the risk of developing Mycobacterium tuberculosis infection. The aim of this study was to determine the association between

Tuberculosis diagnostic methods in buffaloes

Directory of Open Access Journals (Sweden)

Gabriela Capriogli Oliveira

2015-07-01

Full Text Available The low productivity of buffalo herds and condemnation of carcasses in slaughterhouses due to tuberculosis lesions have resulted in increasing economic losses because these animals cannot be treated and must be destroyed by sanitary slaughter. Tuberculosis is a widely distributed zoonosis that affects the beef supply chain of the Brazilian agribusiness economically and socially. Like cattle, buffaloes are sensitive to Mycobacterium bovis, which is the main causative agent of zoonotic tuberculosis. Tuberculosis in buffaloes has been reported in several countries, including Brazil. In order to control and eradicate this disease among cattle and buffaloes in Brazil, the Ministry of Agriculture, Livestock, and Supply created the National Program for the Control and Eradication of Brucellosis and Tuberculosis with the main objective of finding a significant number of disease-free herds throughout the national territory using reliable methods. This review summarizes the main data on the history of occurrence of M. bovis in Brazilian herds and the diagnostic methods for the disease in buffaloes. Little information is available on buffalo tuberculosis. Due to the increasing population of buffaloes and their economic importance, more studies investigating the occurrence and identification of tuberculosis in this species are clearly needed.

MicroRNAs in Obesity, Metabolic Syndrome and Diabetes Mellitus

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Anna Meiliana

2011-04-01

Full Text Available BACKGROUND: MicroRNAs (miRNAs are small regulatory RNAs that play important roles in development of diseases. Several studies have provided evidences showing that miRNAs affect pathways that are fundamental for metabolic control in adipocyte and skeletal muscle differentiations. Some miRNAs have been implicated in lipid, amino acid, and glucose homeostasis. This leads to the possibility that miRNAs may contribute to common metabolic diseases and point to novel therapeutic opportunities based on targeting of miRNAs. CONTENT: miRNAs have been recognized as a class of epigenetic regulators of metabolism and energy homeostasis, primarily because the simultaneous regulation of a large number of target genes can be accomplished by a single miRNA. Emerging evidences suggest that miRNAs play a key role in the pathological development of obesity by affecting adipocyte differentiation. miRNAs have been implicated as novel protagonists in the pathogenesis of Diabetes Mellitus (DM, regulation of insulin production, secretion and action. They also appear to play a role in the development of diabetic complications such as nephropathy and cardiac hypertrophy. SUMMARY: Involvement of miRNAs in glucose and lipid metabolism has provided strong evidences to confirm their roles as key players in regulation of complex metabolic pathways. Additionally, it indicates potential outlook for novel therapeutic strategies in the management of obesity, metabolic syndrome and DM. Further research in this field is needed to ascertain the full potential of miRNAs as novel metabolic biomarkers and potent therapeutic agents against obesity and its metabolic disorders. KEYWORDS: obesity, metabolic syndrome, diabetes, miRNAs, adipogenesis, insulin, pancreatic cells.

Gene function analysis by artificial microRNAs in Physcomitrella patens.

KAUST Repository

Khraiwesh, Basel; Fattash, Isam; Arif, Muhammad Asif; Frank, Wolfgang

2011-01-01

MicroRNAs (miRNAs) are ~21 nt long small RNAs transcribed from endogenous MIR genes which form precursor RNAs with a characteristic hairpin structure. miRNAs control the expression of cognate target genes by binding to reverse complementary

Tuberculosis: A Problem for Lifeguards?

Science.gov (United States)

Skaros, Susan

1996-01-01

Lifeguards run the risk of workplace infection by tuberculosis-carrying swimmers. Even if they work in ventilated, sunlit areas (which reduces risk), they can contract tuberculosis when performing respiratory resuscitation. Without appropriate precautions, lifeguards may be unnecessarily exposed. A tuberculosis infection control plan is needed in…

[Immigrants treated for tuberculosis in Mazovian Center for Treatment of Lung Diseases and Tuberculosis in Otwock].

Science.gov (United States)

Jagodziński, Jacek; Zielonka, Tadeusz M

2010-01-01

Migration of population contributes to the transmission of tuberculosis (TB), particularly multidrug-resistant tuberculosis. In the countries of Western Europe, the immigrants' inflow contributes to the deterioration of the epidemiological situation. Majority of newly detected TB cases in some countries were affirmed among immigrant and foreign born population. In Poland, this problem has not been investigated up to 2005. The aim of the study was the assessment of the occurrence of tuberculosis in foreigners treated in the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis in Otwock. This work had a retrospective character. The number of cases of tuberculosis in foreigners admitted between 2002 and 2007 was calculated from the data base of the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis; 125 patients, whose basic demographic data, bacteriological status and the radiological changes suggested TB, were included in the study. The foreigners made up to 0.5-1.7% all tuberculosis cases treated in Mazovian Centre for Treatment of Lung Diseases and Tuberculosis. Among confirmed cases, twenty four nationalities were seen. Nationals of the Russian Federation (coming from the Republic of Chechnya) formed the biggest group (24%), followed by the Vietnamese (21%) and the Ukrainians (12%). Most of all cases were young men (77%; average age - 34 years). Children made up to 12% of all cases. Tuberculosis of lungs was predominating, and there were culture confirmed extrapulmonary locations in 13.6% of cases. Bacteriological confirmation was achieved in 53% of cases, but up to 22.7% cases were resistant to one of the antituberculosis medicines and 13.6% was multidrug-resistant. Despite the fact, that foreigners made up a small proportion among all the patient treated for tuberculosis in Mazovia, their number systematically increases. High proportion of multidrug-resistant tuberculosis reported in foreign-born cases is a concern.

Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients

DEFF Research Database (Denmark)

Doherty, T Mark; Demissie, Abebech; Olobo, Joseph

2002-01-01

Diagnosis of latent Mycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients...

The role of miRNAs in endometrial cancer.

Science.gov (United States)

Vasilatou, Diamantina; Sioulas, Vasileios D; Pappa, Vasiliki; Papageorgiou, Sotirios G; Vlahos, Nikolaos F

2015-01-01

miRNAs are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Since their discovery, miRNAs have been associated with every cell function including malignant transformation and metastasis. Endometrial cancer is the most common gynecologic malignancy. However, improvement should be made in interobserver agreement on histological typing and individualized therapeutic approaches. This article summarizes the role of miRNAs in endometrial cancer pathogenesis and treatment.

Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues.

Science.gov (United States)

Castellano, Leandro; Stebbing, Justin

2013-03-01

MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly characterized by either ablation or mutation of the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs that could be processed in a canonical or non-canonical manner. A proportion of the newly discovered miRNAs comprises mirtrons, for which we define a new sub-class. Notably, some of these newly discovered miRNAs are generated from untranslated and open reading frames of coding genes, and we experimentally validate these. We also show that many annotated miRNAs do not present miRNA-like features, as they are neither processed by known processing complexes nor loaded on AGO2; this indicates that the current miRNA miRBase database list should be refined and re-defined. Accordingly, a group of them map on ribosomal RNA molecules, whereas others cannot undergo genuine miRNA biogenesis. Notably, a group of annotated miRNAs are Dgcr8 independent and DICER dependent endogenous small interfering RNAs that derive from a unique hairpin formed from a short interspersed nuclear element.

9 CFR 311.2 - Tuberculosis.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 311.2 Section 311.2... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The... pathogenesis of tuberculosis in swine, cattle, sheep, goats, and equines. (a) Carcasses condemned. The entire...

Annotating functional RNAs in genomes using Infernal.

Science.gov (United States)

Nawrocki, Eric P

2014-01-01

Many different types of functional non-coding RNAs participate in a wide range of important cellular functions but the large majority of these RNAs are not routinely annotated in published genomes. Several programs have been developed for identifying RNAs, including specific tools tailored to a particular RNA family as well as more general ones designed to work for any family. Many of these tools utilize covariance models (CMs), statistical models of the conserved sequence, and structure of an RNA family. In this chapter, as an illustrative example, the Infernal software package and CMs from the Rfam database are used to identify RNAs in the genome of the archaeon Methanobrevibacter ruminantium, uncovering some additional RNAs not present in the genome's initial annotation. Analysis of the results and comparison with family-specific methods demonstrate some important strengths and weaknesses of this general approach.

MicroRNAs - A New Generation Molecular Targets for Treating Cellular Diseases

OpenAIRE

Paulmurugan, Ramasamy

2013-01-01

MicroRNAs (miRNAs) are a unique class of non-coding, small RNAs, similar to mRNAs, transcribed by cells, but for entirely different reasons. While mRNAs are transcribed to code for proteins, miRNAs are produced to regulate the production of proteins from mRNAs. miRNAs are central components that tightly and temporally regulating gene expression in cells. Dysregulation of miRNAs expressions in cellular pathogenesis, including cancer, has been reported, and it clearly supports the importance of...

Datos básicos sobre la tuberculosis (Basic Tuberculosis Facts)

Centers for Disease Control (CDC) Podcasts

En este podcast el doctor Kenneth Castro, Director de la División de Eliminación de la Tuberculosis, presenta información básica sobre la prevención, las pruebas y el tratamiento de la tuberculosis.

MicroRNAs horizon in retinoblastoma.

Directory of Open Access Journals (Sweden)

Mojgan Mirakholi

2013-12-01

Full Text Available In the retinoblastoma research, it is of great interest to identify molecular markers associated with the genetics of tumorigenesis. microRNAs (miRNAs are small non-coding RNA molecules that play a regulatory role in many crucial cellular pathways such as differentiation, cell cycle progression, and apoptosis. A body of evidences showed dysregulation of miRNAs in tumor biology and many diseases. They potentially play a significant role in tumorigenesis processes and have been the subject of research in many types of cancers including retinal tumorigenesis. miRNA expression profiling was found to be associated with tumor development, progression and treatment. These associations demonstrate the putative applications of miRNAs in monitoring of different aspect of tumors consisting diagnostic, prognostic and therapeutic. Herein, we review the current literature concerning to the study of miRNA target recognition, function to tumorigenesis and treatment in retinoblastoma. Identification the specific miRNA biomarkers associated with retinoblastoma cancer may help to establish new therapeutic approaches for salvage affected eyes in patients.

Imaging of Esophageal Tuberculosis

International Nuclear Information System (INIS)

Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.; Lal, A.; Gulati, M.; Suri, S.

2003-01-01

Purpose: To evaluate the various radiological abnormalities in patients with proven esophageal tuberculosis. Material and Methods: The case records of 23 patients with proven esophageal tuberculosis were evaluated retrospectively for various radiological abnormalities. Twenty-two patients had secondary involvement of esophagus in the form of direct extension of mediastinal and pulmonary tuberculosis or spinal tuberculosis. Only 1 patient had primary involvement of the esophagus with no evidence of disease elsewhere. The diagnosis was confirmed by endoscopic and CT-guided biopsy/aspiration cytology in 7 and 6 cases, respectively. Diagnosis was made on the basis of surgical biopsy of lymph node and autopsy in 1 patient each. In the remaining 8 patients the diagnosis was based on radiological and endoscopic findings and the response to antituberculous treatment. Results: Chest radiography (CXR) was abnormal in 65% patients. While the findings were non-conclusive for esophageal tuberculosis, characteristic lesions of tuberculosis in lungs or spine were suggestive of tuberculous etiology. In 15 patients, CT of the chest confirmed the corresponding CXR findings and also showed additional findings of mediastinal lymphadenopathy when CXR was normal. Fourteen patients showed mediastinal lymphadenopathy on CT of the chest. In all these patients, more than one group of lymph nodes was involved. The characteristic hypodense center of lymph nodes suggestive of tuberculosis was seen in 12 patients. Radiological abnormalities seen in barium swallow examination were extrinsic compression, traction diverticula, strictures, sinus/fistulous tracts, kinking and pseudotumor mass of esophagus in decreasing order of frequency. The middle third of the esophagus was found to be the most frequent site of involvement

The Role of MicroRNAs in Kidney Disease

Directory of Open Access Journals (Sweden)

Sydwell Mukhadi

2015-11-01

Full Text Available MicroRNAs (miRNAs are short noncoding RNAs that regulate pathophysiological processes that suppress gene expression by binding to messenger RNAs. These biomolecules can be used to study gene regulation and protein expression, which will allow better understanding of many biological processes such as cell cycle progression and apoptosis that control the fate of cells. Several pathways have also been implicated to be involved in kidney diseases such as Transforming Growth Factor-β, Mitogen-Activated Protein Kinase signaling, and Wnt signaling pathways. The discovery of miRNAs has provided new insights into kidney pathologies and may provide new innovative and effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including renal cell carcinoma, diabetic nephropathy, nephritic syndrome, renal fibrosis, lupus nephritis and acute pyelonephritis. MiRNAs are implicated as playing a role in these diseases due to their role in apoptosis, cell proliferation, differentiation and development. As miRNAs have been detected in a stable condition in different biological fluids, they have the potential to be tools to study the pathogenesis of human diseases with a great potential to be used in disease prognosis and diagnosis. The purpose of this review is to examine the role of miRNA in kidney disease.

The roles of non-coding RNAs in cardiac regenerative medicine

Directory of Open Access Journals (Sweden)

Oi Kuan Choong

2017-06-01

Full Text Available The emergence of non-coding RNAs (ncRNAs has challenged the central dogma of molecular biology that dictates that the decryption of genetic information starts from transcription of DNA to RNA, with subsequent translation into a protein. Large numbers of ncRNAs with biological significance have now been identified, suggesting that ncRNAs are important in their own right and their roles extend far beyond what was originally envisaged. ncRNAs do not only regulate gene expression, but are also involved in chromatin architecture and structural conformation. Several studies have pointed out that ncRNAs participate in heart disease; however, the functions of ncRNAs still remain unclear. ncRNAs are involved in cellular fate, differentiation, proliferation and tissue regeneration, hinting at their potential therapeutic applications. Here, we review the current understanding of both the biological functions and molecular mechanisms of ncRNAs in heart disease and describe some of the ncRNAs that have potential heart regeneration effects. Keywords: Non-coding RNAs, Cardiac regeneration, Cardiac fate, Proliferation, Differentiation, Reprograming

Viruses and miRNAs: More Friends than Foes.

Science.gov (United States)

Bruscella, Patrice; Bottini, Silvia; Baudesson, Camille; Pawlotsky, Jean-Michel; Feray, Cyrille; Trabucchi, Michele

2017-01-01

There is evidence that eukaryotic miRNAs (hereafter called host miRNAs) play a role in the replication and propagation of viruses. Expression or targeting of host miRNAs can be involved in cellular antiviral responses. Most times host miRNAs play a role in viral life-cycles and promote infection through complex regulatory pathways. miRNAs can also be encoded by a viral genome and be expressed in the host cell. Viral miRNAs can share common sequences with host miRNAs or have totally different sequences. They can regulate a variety of biological processes involved in viral infection, including apoptosis, evasion of the immune response, or modulation of viral life-cycle phases. Overall, virus/miRNA pathway interaction is defined by a plethora of complex mechanisms, though not yet fully understood. This article review summarizes recent advances and novel biological concepts related to the understanding of miRNA expression, control and function during viral infections. The article also discusses potential therapeutic applications of this particular host-pathogen interaction.

On the classification of long non-coding RNAs

KAUST Repository

Ma, Lina

2013-06-01

Long non-coding RNAs (lncRNAs) have been found to perform various functions in a wide variety of important biological processes. To make easier interpretation of lncRNA functionality and conduct deep mining on these transcribed sequences, it is convenient to classify lncRNAs into different groups. Here, we summarize classification methods of lncRNAs according to their four major features, namely, genomic location and context, effect exerted on DNA sequences, mechanism of functioning and their targeting mechanism. In combination with the presently available function annotations, we explore potential relationships between different classification categories, and generalize and compare biological features of different lncRNAs within each category. Finally, we present our view on potential further studies. We believe that the classifications of lncRNAs as indicated above are of fundamental importance for lncRNA studies, helpful for further investigation of specific lncRNAs, for formulation of new hypothesis based on different features of lncRNA and for exploration of the underlying lncRNA functional mechanisms. © 2013 Landes Bioscience.

The application of microRNAs in cancer diagnostics

DEFF Research Database (Denmark)

Sørensen, Karina Dalsgaard; Ostenfeld, Marie Stampe; Kristensen, Helle

2012-01-01

hallmark of human cancer. Furthermore, miRNAs have been found to be a new class of promising cancer biomarkers with potential to improve the accuracy of diagnosis and prognosis in several hematologic and solid malignancies, as well as to predict response to specific treatments. Recent studies have......MicroRNAs (miRNAs) play important biological roles in cancer development and progression. During the past decade, widespread use of novel high-throughput technologies for miRNA profiling (e.g., microarrays and next-generation sequencing) has revealed deregulation of miRNA expression as a common...... identified exosome-associated tumor-derived miRNAs in, e.g., blood samples from cancer patients, suggesting that miRNAs may be useful as circulation biomarkers for noninvasive diagnostic testing. In this chapter, we review the current state of development of miRNAs as cancer biomarkers with examples from...

Tuberculosis among Children in Alaska.

Science.gov (United States)

Gessner, Bradford D.

1997-01-01

The incidence of tuberculosis among Alaskan children under 15 was more than twice the national rate, with Alaska Native children showing a much higher incidence. Children with household exposure to adults with active tuberculosis had a high risk of infection. About 22 percent of pediatric tuberculosis cases were identified through school…

Childhood Tuberculosis, Still with Us...

Science.gov (United States)

Chaulet, Pierre; And Others

1992-01-01

The first section of this report on childhood tuberculosis in developed and developing countries discusses the epidemiology of tuberculosis in children. Information is presented on: (1) sources and prevalence of infection; (2) risks, frequency, and types of tuberculosis; (3) mortality rates; and (4) the relation of poverty and AIDS to…

Urinary microRNAs as potential biomarkers of pesticide exposure

International Nuclear Information System (INIS)

Weldon, Brittany A.; Shubin, Sara Pacheco; Smith, Marissa N.; Workman, Tomomi; Artemenko, Alexander; Griffith, William C.; Thompson, Beti; Faustman, Elaine M.

2016-01-01

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. - Highlights: • A novel method to identify microRNA biomarkers in urinary samples is proposed. • Six miRNAs have been identified as associated with occupational farm work and pesticide exposure. • An observed seasonal difference suggests transient

Urinary microRNAs as potential biomarkers of pesticide exposure

Energy Technology Data Exchange (ETDEWEB)

Weldon, Brittany A.; Shubin, Sara Pacheco; Smith, Marissa N.; Workman, Tomomi; Artemenko, Alexander; Griffith, William C. [Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA (United States); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Thompson, Beti [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Faustman, Elaine M., E-mail: faustman@uw.edu [Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA (United States); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States)

2016-12-01

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. - Highlights: • A novel method to identify microRNA biomarkers in urinary samples is proposed. • Six miRNAs have been identified as associated with occupational farm work and pesticide exposure. • An observed seasonal difference suggests transient

MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs.

Science.gov (United States)

Avesson, Lotta; Reimegård, Johan; Wagner, E Gerhart H; Söderbom, Fredrik

2012-10-01

The RNA interference machinery has served as a guardian of eukaryotic genomes since the divergence from prokaryotes. Although the basic components have a shared origin, silencing pathways directed by small RNAs have evolved in diverse directions in different eukaryotic lineages. Micro (mi)RNAs regulate protein-coding genes and play vital roles in plants and animals, but less is known about their functions in other organisms. Here, we report, for the first time, deep sequencing of small RNAs from the social amoeba Dictyostelium discoideum. RNA from growing single-cell amoebae as well as from two multicellular developmental stages was sequenced. Computational analyses combined with experimental data reveal the expression of miRNAs, several of them exhibiting distinct expression patterns during development. To our knowledge, this is the first report of miRNAs in the Amoebozoa supergroup. We also show that overexpressed miRNA precursors generate miRNAs and, in most cases, miRNA* sequences, whose biogenesis is dependent on the Dicer-like protein DrnB, further supporting the presence of miRNAs in D. discoideum. In addition, we find miRNAs processed from hairpin structures originating from an intron as well as from a class of repetitive elements. We believe that these repetitive elements are sources for newly evolved miRNAs.

Dissection of functional lncRNAs in Alzheimer's disease by construction and analysis of lncRNA-mRNA networks based on competitive endogenous RNAs.

Science.gov (United States)

Wang, Lian-Kun; Chen, Xiao-Feng; He, Dan-Dan; Li, You; Fu, Jin

2017-04-08

Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly, and intracellular neurofibrillary tangles (NFTs) are one of the pathological features of AD. Recent studies have suggested long noncoding RNAs (lncRNAs) play important roles in AD. Competing endogenous RNAs (ceRNAs) is a mechanism that has recently been proposed, in which lncRNAs compete for common miRNA-binding sites with mRNAs. However, the roles of lncRNAs and ceRNA in AD NFTs is limited. In this study, we constructed a global triple network based on ceRNA theory, then an AD NFT lncRNA-mRNA network (NFTLMN) was generated. By analyzing the NFTLMN, three lncRNAs (AP000265.1, KB-1460A1.5 and RP11-145M9.4), which are highly related with AD NFTs were identified. To further explore the cross-talk between mRNAs and lncRNAs, a clustering module analysis was performed on the NFTLMN and two AD NFT related modules were identified. Our study provides a better understanding of the molecular basis of AD NFTs and may offer novel treatment strategies for AD. Copyright © 2016. Published by Elsevier Inc.

Tuberculosis treatment outcome in a tertiary care setting

International Nuclear Information System (INIS)

Bukhary, Zakeya A.; Alrajhi, Abdulrahman A.

2007-01-01

The outcome of the chemotherapy for pulmonary, extraplumonary and disseminated tuberculosis is not well documented, especially in developing countries. This study assessed tuberculosis treatment outcome, cure-to-treatment ratio and mortality among all types of tuberculosis patients in a tertiary care setting in Saudi Arabia. All cases diagnosed and treated for active Mycobacterium tuberculosis infection between 1991 and 2000 were included retrospectively. Data collected included type of tuberculosis involvement, treatment outcome, relapse and co-morbidities. Over a ten-year period, 535 case of tuberculosis were diagnosed and treated. Isolated pulmonary tuberculosis was identified in 141 cases (26.4%), extrapulmonary tuberculosis in 339 cases (63.3%). Co-morbidities were noted in 277 (52%) patients. Immunosuppression was found in 181 (34%) cases. The cure rate was 82%. The cure-to-treatment ratio was 86% in extrapulmonary tuberculosis and 65% in disseminated tuberculosis. Overall mortality was 18%. Disseminated tuberculosis had the highest mortality (34.9%), followed by pulmonary (21.8%), the extrapulmonary tuberculosis (13.6%). Forty-seven percent of all mortalities were directly related to tuberculosis. Relapse was documented in 14 out of 349 patients (4%) who had 24 months of follow-up. Despite tertiary care support, complicated tuberculosis carries a high mortality. Earlier diagnosis and complete appropriate chemotherapy are essential for improved outcome. (author)

Extrapulmonary involvement in pediatric tuberculosis.

Science.gov (United States)

Kritsaneepaiboon, Supika; Andres, Mariaem M; Tatco, Vincent R; Lim, Cielo Consuelo Q; Concepcion, Nathan David P

2017-09-01

Tuberculosis in childhood is clinically challenging, but it is a preventable and treatable disease. Risk factors depend on age and immunity status. The most common form of pediatric tuberculosis is pulmonary disease, which comprises more than half of the cases. Other forms make up the extrapulmonary tuberculosis that involves infection of the lymph nodes, central nervous system, gastrointestinal system, hepatobiliary tree, and renal and musculoskeletal systems. Knowledge of the imaging characteristics of pediatric tuberculosis provides clues to diagnosis. This article aims to review the imaging characteristics of common sites for extrapulmonary tuberculous involvement in children.

38 CFR 3.959 - Tuberculosis.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Tuberculosis. 3.959..., Compensation, and Dependency and Indemnity Compensation Protection § 3.959 Tuberculosis. Any veteran who, on...) tuberculosis may receive compensation under 38 U.S.C. 1114(q) and 1156 as in effect before August 20, 1968...

MicroRNAs in addiction: adaptation's middlemen?

Science.gov (United States)

Li, M D; van der Vaart, A D

2011-12-01

A central question in addiction is how drug-induced changes in synaptic signaling are converted into long-term neuroadaptations. Emerging evidence reveals that microRNAs (miRNAs) have a distinct role in this process through rapid response to cellular signals and dynamic regulation of local mRNA transcripts. Because each miRNA can target hundreds of mRNAs, relative changes in the expression of miRNAs can greatly impact cellular responsiveness, synaptic plasticity and transcriptional events. These diverse consequences of miRNA action occur through coordination with genes implicated in addictions, the most compelling of these being the neurotrophin BDNF, the transcription factor cAMP-responsive element-binding protein (CREB) and the DNA-binding methyl CpG binding protein 2 (MeCP2). In this study, we review the recent progress in the understanding of miRNAs in general mechanisms of plasticity and neuroadaptation and then focus on specific examples of miRNA regulation in the context of addiction. We conclude that miRNA-mediated gene regulation is a conserved means of converting environmental signals into neuronal response, which holds significant implications for addiction and other psychiatric illnesses.

What We Know About Tuberculosis Transmission: An Overview.

Science.gov (United States)

Churchyard, Gavin; Kim, Peter; Shah, N Sarita; Rustomjee, Roxana; Gandhi, Neel; Mathema, Barun; Dowdy, David; Kasmar, Anne; Cardenas, Vicky

2017-11-03

Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Non-Coding RNAs in Muscle Dystrophies

Directory of Open Access Journals (Sweden)

Alessandra Ferlini

2013-09-01

Full Text Available ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies.

Non-coding RNAs in endometriosis: a narrative review.

Science.gov (United States)

Panir, Kavita; Schjenken, John E; Robertson, Sarah A; Hull, M Louise

2018-04-25

Endometriosis is a benign gynaecological disorder, which affects 10% of reproductive-aged women and is characterized by endometrial cells from the lining of the uterus being found outside the uterine cavity. However, the pathophysiological mechanisms causing the development of this heterogeneous disease remain enigmatic, and a lack of effective biomarkers necessitates surgical intervention for diagnosis. There is international recognition that accurate non-invasive diagnostic tests and more effective therapies are urgently needed. Non-coding RNA (ncRNA) molecules, which are important regulators of cellular function, have been implicated in many chronic conditions. In endometriosis, transcriptome profiling of tissue samples and functional in vivo and in vitro studies demonstrate that ncRNAs are key contributors to the disease process. In this review, we outline the biogenesis of various ncRNAs relevant to endometriosis and then summarize the evidence indicating their roles in regulatory pathways that govern disease establishment and progression. Articles from 2000 to 2016 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: ncRNA and reproduction; ncRNA and endometriosis; miRNA and endometriosis; lncRNA and endometriosis; siRNA and endometriosis; endometriosis; endometrial; cervical; ovary; uterus; reproductive tract. All articles were independently screened for eligibility by the authors. This review integrates extensive information from all relevant published studies focusing on microRNAs, long ncRNAs and short inhibitory RNAs in endometriosis. We outline the biological function and synthesis of microRNAs, long ncRNAs and short inhibitory RNAs and provide detailed findings from human research as well as functional studies carried out both in vitro and in vivo, including animal models. Although variability in findings between individual studies exists, collectively, the

MicroRNAs: role and therapeutic targets in viral hepatitis

NARCIS (Netherlands)

van der Ree, Meike H.; de Bruijne, Joep; Kootstra, Neeltje A.; Jansen, Peter Lm; Reesink, Hendrik W.

2014-01-01

MicroRNAs regulate gene expression by binding to the 3'-untranslated region (UTR) of target messenger RNAs (mRNAs). The importance of microRNAs has been shown for several liver diseases, for example, viral hepatitis. MicroRNA-122 is highly abundant in the liver and is involved in the regulation of

MicroRNAs in mantle cell lymphoma

DEFF Research Database (Denmark)

Husby, Simon; Geisler, Christian; Grønbæk, Kirsten

2013-01-01

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. New treatment modalities, including intensive induction regimens with immunochemotherapy and autologous stem cell transplant, have improved survival. However, many patients still relapse, and there is a need...... for novel therapeutic strategies. Recent progress has been made in the understanding of the role of microRNAs (miRNAs) in MCL. Comparisons of tumor samples from patients with MCL with their normal counterparts (naive B-cells) have identified differentially expressed miRNAs with roles in cellular growth...

Brain expressed microRNAs implicated in schizophrenia etiology

DEFF Research Database (Denmark)

Hansen, Thomas; Olsen, Line; Lindow, Morten

2007-01-01

Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors...

Isolation and Identification of miRNAs in Jatropha curcas

Science.gov (United States)

Wang, Chun Ming; Liu, Peng; Sun, Fei; Li, Lei; Liu, Peng; Ye, Jian; Yue, Gen Hua

2012-01-01

MicroRNAs (miRNAs) are small noncoding RNAs that play crucial regulatory roles by targeting mRNAs for silencing. To identify miRNAs in Jatropha curcas L, a bioenergy crop, cDNA clones from two small RNA libraries of leaves and seeds were sequenced and analyzed using bioinformatic tools. Fifty-two putative miRNAs were found from the two libraries, among them six were identical to known miRNAs and 46 were novel. Differential expression patterns of 15 miRNAs in root, stem, leave, fruit and seed were detected using quantitative real-time PCR. Ten miRNAs were highly expressed in fruit or seed, implying that they may be involved in seed development or fatty acids synthesis in seed. Moreover, 28 targets of the isolated miRNAs were predicted from a jatropha cDNA library database. The miRNA target genes were predicted to encode a broad range of proteins. Sixteen targets had clear BLASTX hits to the Uniprot database and were associated with genes belonging to the three major gene ontology categories of biological process, cellular component, and molecular function. Four targets were identified for JcumiR004. By silencing JcumiR004 primary miRNA, expressions of the four target genes were up-regulated and oil composition were modulated significantly, indicating diverse functions of JcumiR004. PMID:22419887

Identification of microRNA-like RNAs in Ophiocordyceps sinensis.

Science.gov (United States)

Zhang, Wen; Li, Xiaona; Ma, Lina; Urrehman, Uzair; Bao, Xilinqiqige; Zhang, Yujing; Zhang, Chen-Yu; Hou, Dongxia; Zhou, Zhen

2018-03-27

Ophiocordyceps sinensis is well known as a traditional Chinese medicine and has widely been used for over 2,000 years to stimulate immune system, decrease blood pressure and to inhibit tumor growth. While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less studied until the discovery of microRNA-like RNA (milRNA). High-throughput sequencing and bioinformatics approaches were used to identify conserved and novel milRNAs in O. sinensis. 40 conserved milRNAs were identified, while 23 pre-miRNA candidates encoding 31 novel milRNAs were predicted. Furthermore, the potential target genes of milRNAs in human were predicted and gene ontology analysis was applied to these genes. Enrichment analysis of GO-represented biological process showed that target genes of both conserved and novel milRNAs are involved in development, metabolic and immune processes, indicating the potential roles of milRNAs of O. sinensis in pharmacological effects as health food and traditional Chinese medicine. This study is the first report on genome-wide analysis of milRNAs in O. sinensis and it provides a useful resource to further study the potential roles of milRNAs as active components of O. sinensis in health food or traditional Chinese medicine.

The interplay between noncoding RNAs and insulin in diabetes.

Science.gov (United States)

Tian, Yan; Xu, Jia; Du, Xiao; Fu, Xianghui

2018-04-10

Noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, regulate various biological processes and are involved in the initiation and progression of human diseases. Insulin, a predominant hormone secreted from pancreatic β cells, is an essential factor in regulation of systemic metabolism through multifunctional insulin signaling. Insulin production and action are tightly controlled. Dysregulations of insulin production and action can impair metabolic homeostasis, and eventually lead to the development of multiple metabolic diseases, especially diabetes. Accumulating data indicates that ncRNAs modulate β cell mass, insulin synthesis, secretion and signaling, and their role in diabetes is dramatically emerging. This review summarizes our current knowledge of ncRNAs as regulators of insulin, with particular emphasis on the implications of this interplay in the development of diabetes. We outline the role of ncRNAs in pancreatic β cell mass and function, which is critical for insulin production and secretion. We also highlight the involvement of ncRNAs in insulin signaling in peripheral tissues including liver, muscle and adipose, and discuss ncRNA-mediated inter-organ crosstalk under diabetic conditions. A more in-depth understanding of the interplay between ncRNAs and insulin may afford valuable insights and novel therapeutic strategies for treatment of diabetes, as well as other human diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Integration of Bacterial Small RNAs in Regulatory Networks.

Science.gov (United States)

Nitzan, Mor; Rehani, Rotem; Margalit, Hanah

2017-05-22

Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA-target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript. Finally, we discuss the competition effects in posttranscriptional regulatory networks that may arise over shared targets, shared regulators, and shared resources and how they may lead to signal propagation across the network.

Tuberculosis of the cervical spine

African Journals Online (AJOL)

Tuberculosis of the cervical spine is rare, comprising 3 -. 5% of cases of tuberculosis of the spine. Eight patients with tuberculosis of the cervicaJ spine seen during 1989 -. 1992 were reviewed. They all presented with neck pain. The 4 children presented with a kyphotic deformity. In all the children the disease was extensive, ...

History, Discovery, and Classification of lncRNAs.

Science.gov (United States)

Jarroux, Julien; Morillon, Antonin; Pinskaya, Marina

2017-01-01

The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of

Profile of cerebrospinal microRNAs in fibromyalgia.

Directory of Open Access Journals (Sweden)

Jan L Bjersing

Full Text Available Fibromyalgia (FM is characterized by chronic pain and reduced pain threshold. The pathophysiology involves disturbed neuroendocrine function, including impaired function of the growth hormone/insulin-like growth factor-1 axis. Recently, microRNAs have been shown to be important regulatory factors in a number of diseases. The aim of this study was to try to identify cerebrospinal microRNAs with expression specific for FM and to determine their correlation to pain and fatigue.The genome-wide profile of microRNAs in cerebrospinal fluid was assessed in ten women with FM and eight healthy controls using real-time quantitative PCR. Pain thresholds were examined by algometry. Levels of pain (FIQ pain were rated on a 0-100 mm scale (fibromyalgia impact questionnaire, FIQ. Levels of fatigue (FIQ fatigue were rated on a 0-100 mm scale using FIQ and by multidimensional fatigue inventory (MFI-20 general fatigue (MFIGF.Expression levels of nine microRNAs were significantly lower in patients with FM patients compared to healthy controls. The microRNAs identified were miR-21-5p, miR-145-5p, miR-29a-3p, miR-99b-5p, miR-125b-5p, miR-23a-3p, 23b-3p, miR-195-5p, miR-223-3p. The identified microRNAs with significantly lower expression in FM were assessed with regard to pain and fatigue. miR-145-5p correlated positively with FIQ pain (r=0.709, p=0.022, n=10 and with FIQ fatigue (r=0.687, p=0.028, n=10.To our knowledge, this is the first study to show a disease-specific pattern of cerebrospinal microRNAs in FM. We have identified nine microRNAs in cerebrospinal fluid that differed between FM patients and healthy controls. One of the identified microRNAs, miR-145 was associated with the cardinal symptoms of FM, pain and fatigue.

Profile of cerebrospinal microRNAs in fibromyalgia.

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Bjersing, Jan L; Lundborg, Christopher; Bokarewa, Maria I; Mannerkorpi, Kaisa

2013-01-01

Fibromyalgia (FM) is characterized by chronic pain and reduced pain threshold. The pathophysiology involves disturbed neuroendocrine function, including impaired function of the growth hormone/insulin-like growth factor-1 axis. Recently, microRNAs have been shown to be important regulatory factors in a number of diseases. The aim of this study was to try to identify cerebrospinal microRNAs with expression specific for FM and to determine their correlation to pain and fatigue. The genome-wide profile of microRNAs in cerebrospinal fluid was assessed in ten women with FM and eight healthy controls using real-time quantitative PCR. Pain thresholds were examined by algometry. Levels of pain (FIQ pain) were rated on a 0-100 mm scale (fibromyalgia impact questionnaire, FIQ). Levels of fatigue (FIQ fatigue) were rated on a 0-100 mm scale using FIQ and by multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Expression levels of nine microRNAs were significantly lower in patients with FM patients compared to healthy controls. The microRNAs identified were miR-21-5p, miR-145-5p, miR-29a-3p, miR-99b-5p, miR-125b-5p, miR-23a-3p, 23b-3p, miR-195-5p, miR-223-3p. The identified microRNAs with significantly lower expression in FM were assessed with regard to pain and fatigue. miR-145-5p correlated positively with FIQ pain (r=0.709, p=0.022, n=10) and with FIQ fatigue (r=0.687, p=0.028, n=10). To our knowledge, this is the first study to show a disease-specific pattern of cerebrospinal microRNAs in FM. We have identified nine microRNAs in cerebrospinal fluid that differed between FM patients and healthy controls. One of the identified microRNAs, miR-145 was associated with the cardinal symptoms of FM, pain and fatigue.

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

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Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

2011-01-01

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

Radiological manifestations of pulmonary tuberculosis

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Andreu, J. E-mail: andreuj@hg.vhebron.es; Caceres, J.; Pallisa, E.; Martinez-Rodriguez, M

2004-08-01

Pulmonary tuberculosis (TB) is a common worldwide lung infection. The radiological features show considerable variation, but in most cases they are characteristic enough to suggest the diagnosis. Classically, tuberculosis is divided into primary, common in childhood, and postprimary, usually presenting in adults. The most characteristic radiological feature in primary tuberculosis is lymphadenopathy. On enhanced CT, hilar and mediastinal nodes with a central hypodense area suggest the diagnosis. Cavitation is the hallmark of postprimary tuberculosis and appears in around half of patients. Patchy, poorly defined consolidation in the apical and posterior segments of the upper lobes, and in the superior segment of the lower lobe is also commonly observed. Several complications are associated with tuberculous infection, such as hematogenous dissemination (miliary tuberculosis) or extension to the pleura, resulting in pleural effusion. Late complications of tuberculosis comprise a heterogeneous group of processes including tuberculoma, bronchial stenosis bronchiectasis, broncholithiasis, aspergilloma, bronchoesophageal fistula and fibrosing mediastinitis. Radiology provides essential information for the management and follow up of these patients and is extremely valuable for monitoring complications.

MicroRNAs in Experimental Models of Movement Disorders

Directory of Open Access Journals (Sweden)

Soon-Tae Lee

2011-10-01

Full Text Available MicroRNAs (miRNAs are small RNAs comprised of 20–25 nucleotides that regulates gene expression by inducing translational repression or degradation of target mRNA. The importance of miRNAs as a mediator of disease pathogenesis and therapeutic targets is rapidly emerging in neuroscience, as well as oncology, immunology, and cardiovascular diseases. In Parkinson’s disease and related disorders, multiple studies have identified the implications of specific miRNAs and the polymorphisms of miRNA target genes during the disease pathogenesis. With a focus on Parkinson’s disease, spinocerebellar ataxia, hereditary spastic paraplegia, and Huntington’s disease, this review summarizes and interprets the observations, and proposes future research topics in this field.

The imaging feature of multidrug-resistant tuberculosis

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Yang Jun; Zhou Xinhua; Li Xi; Fu Yuhong; Zheng Suhua; Lv Pingxin; Ma Daqing

2004-01-01

Objective: To evaluate the imaging features of multidrug-resistant tuberculosis by collecting multidrug-resistant tuberculosis verified by test of drug-sensitivity, which defined as resistance to three anti-tuberculosis drugs. Methods:Fifty-one cases of multidrug-resistant tuberculosis were categorized as group of observed, and 46 cases of drug sensitive tuberculosis were categorized as control. Cultures were positive for Mycobacterium tuberculosis in all cases with no other illness such as diabetes mellitus. All patients had chest radiographs available for review, while 64 cases had tomography and 30 cases had CT during the same time. All images were analyzed by three of the radiologists, disagreement among them was discussed and a consensus was reached. Results: There was no difference in the distribution of lesions between the multidrug-resistant tuberculosis group and control group. However, the radiological findings in the multidrug-resistant tuberculosis group were significantly more common than in control group, such as multiple nodules (10 cases), disseminated foci (23 cases), cavity (9 cases), and complications (10 cases). Comparing the dynamic cases, deteriorating cases were more commonly seen in observed group than in control group, while improved cases were less in observed group than in control group. Conclusion: Multidrug-resistant tuberculosis is the most serious tuberculosis, which is characterized with significant activity, more disseminated foci, cavity, and complications. The lesion deteriorated while correct anti-tuberculosis treatment is applied. (authors)

The Role of MicroRNAs in Bovine Infection and Immunity

Directory of Open Access Journals (Sweden)

Nathan eLawless

2014-11-01

Full Text Available MicroRNAs (miRNAs are a class of small, non-coding RNAs that are recognised as critical regulators of immune gene expression during infection. Many immunologically significant human miRNAs have been found to be conserved in agriculturally important species, including cattle. Discovering how bovine miRNAs mediate the immune defence during infection is critical to understanding the aetiology of the most prevalent bovine diseases. Here, we review current knowledge of miRNAs in the bovine genome, and discuss the advances in understanding of miRNAs as regulators of immune cell function, and bovine immune response activation, regulation, and resolution. Finally, we consider the future perspectives on miRNAs in bovine viral disease, their role as potential biomarkers and in therapy.

Role of Virus-Encoded microRNAs in Avian Viral Diseases

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Yongxiu Yao

2014-03-01

Full Text Available With total dependence on the host cell, several viruses have adopted strategies to modulate the host cellular environment, including the modulation of microRNA (miRNA pathway through virus-encoded miRNAs. Several avian viruses, mostly herpesviruses, have been shown to encode a number of novel miRNAs. These include the highly oncogenic Marek’s disease virus-1 (26 miRNAs, avirulent Marek’s disease virus-2 (36 miRNAs, herpesvirus of turkeys (28 miRNAs, infectious laryngotracheitis virus (10 miRNAs, duck enteritis virus (33 miRNAs and avian leukosis virus (2 miRNAs. Despite the closer antigenic and phylogenetic relationship among some of the herpesviruses, miRNAs encoded by different viruses showed no sequence conservation, although locations of some of the miRNAs were conserved within the repeat regions of the genomes. However, some of the virus-encoded miRNAs showed significant sequence homology with host miRNAs demonstrating their ability to serve as functional orthologs. For example, mdv1-miR-M4-5p, a functional ortholog of gga-miR-155, is critical for the oncogenicity of Marek’s disease virus. Additionally, we also describe the potential association of the recently described avian leukosis virus subgroup J encoded E (XSR miRNA in the induction of myeloid tumors in certain genetically-distinct chicken lines. In this review, we describe the advances in our understanding on the role of virus-encoded miRNAs in avian diseases.

Regulatory Non-Coding RNAs in Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Alessandro Rosa

2013-07-01

Full Text Available The most part of our genome encodes for RNA transcripts are never translated into proteins. These include families of RNA molecules with a regulatory function, which can be arbitrarily subdivided in short (less than 200 nucleotides and long non-coding RNAs (ncRNAs. MicroRNAs, which act post-transcriptionally to repress the function of target mRNAs, belong to the first group. Included in the second group are multi-exonic and polyadenylated long ncRNAs (lncRNAs, localized either in the nucleus, where they can associate with chromatin remodeling complexes to regulate transcription, or in the cytoplasm, acting as post-transcriptional regulators. Pluripotent stem cells, such as embryonic stem cells (ESCs or induced pluripotent stem cells (iPSCs, represent useful systems for modeling normal development and human diseases, as well as promising tools for regenerative medicine. To fully explore their potential, however, a deep understanding of the molecular basis of stemness is crucial. In recent years, increasing evidence of the importance of regulation by ncRNAs in pluripotent cells is accumulating. In this review, we will discuss recent findings pointing to multiple roles played by regulatory ncRNAs in ESC and iPSCs, where they act in concert with signaling pathways, transcriptional regulatory circuitries and epigenetic factors to modulate the balance between pluripotency and differentiation.

[Treatment of tuberculosis in patients with comorbidities].

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Abe, Masahiro; Fujita, Akira

2013-12-01

Early detection and appropriate treatment are the keys to tuberculosis control. In particular, providing appropriate treatment for tuberculosis in patients with HIV infection, rheumatoid arthritis (RA), chronic hepatic disease, or renal failure necessitating hemodialysis, and taking appropriate measures against adverse reactions to antituberculosis drugs are issues of critical importance. This mini-symposium, four experts explained the current status of "treatment of tuberculosis in patients with comorbidities" and proposed measures to address these problems. Dr. Aoki talked about "HIV infection complicated by tuberculosis." To the next, Dr. Yoshinaga gave a talk on "treatment of tuberculosis in RA patients receiving biological agents. Further, Dr. Sasaki lectured on "tuberculosis in patients with hepatic disease/impairment". Lastly, Dr. Takamori gave a lecture on "tuberculosis in patients with renal disease and those on hemodialysis. Tuberculosis patients often have some underlying diseases, and adverse reactions caused by antituberculosis drugs, such as hepatic and renal impairments, are matters of concern. I believe that this mini-symposium has provided useful information for physicians engaged in tuberculosis treatment and for many other healthcare professionals as well.

Active case finding of tuberculosis in Europe: a Tuberculosis Network European Trials Group (TBNET) survey