scholarly journals Binary Intermetallics in the 70 atom % R Region of Two R–Pd Systems (R = Tb and Er): Hidden, Obscured, or Nonexistent?

2020 ◽  
Vol 59 (15) ◽  
pp. 10802-10812
Author(s):  
Thomas Bell ◽  
Volodymyr Smetana ◽  
Anja-Verena Mudring ◽  
Gerd H. Meyer
Keyword(s):  
R Region

Characterization of the inducer of short transcripts, a human immunodeficiency virus type 1 transcriptional element that activates the synthesis of short RNAs

1993 ◽  
Vol 13 (2) ◽  
pp. 1251-1263
Author(s):  
M Sheldon ◽  
R Ratnasabapathy ◽  
N Hernandez
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Regulatory Region ◽  
Short Rnas ◽  
Immunodeficiency Virus ◽  
R Region ◽  
Transcription Complexes ◽  
Hiv 1

The inducer of short transcripts, or IST, is an unusual transcriptional element located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter. IST activates HIV-1 transcription, but the resulting RNAs are short and end at approximately position +59. IST, therefore, appears to promote the formation of transcription complexes that are unable to elongate efficiently. This activity contrasts with that of TAR, the target for Tat trans-activation, which upon binding of the viral protein Tat promotes the formation of transcription complexes capable of efficient elongation through the entire viral genome. We have localized and characterized the IST element. Our results indicate that IST is located mainly between positions -5 and +26, although the sequences from positions +40 to +59 also contribute to IST activity. Unlike TAR, which is an RNA element, IST appears to be a DNA element. Thus, the HIV-1 R region is a complex regulatory region with RNA and DNA elements that promote the formation of transcription complexes with different elongation properties.

scholarly journals Antisense Transcription in Gammaretroviruses as a Mechanism of Insertional Activation of Host Genes

2010 ◽  
Vol 84 (8) ◽  
pp. 3780-3788 ◽  
Author(s):  
Mads Heilskov Rasmussen ◽  
Borja Ballarín-González ◽  
Jinghua Liu ◽  
Louise Berkhoudt Lassen ◽  
Annette Füchtbauer ◽  
...  
Keyword(s):  
B Cell ◽  
Leukemia Virus ◽  
Negative Polarity ◽  
Antisense Transcription ◽  
B Cell Lymphomas ◽  
Eukaryotic Transcription ◽  
R Region ◽  
Rapid Amplification ◽  
Host Genes

ABSTRACT Transcription of retroviruses is initiated at the U3-R region boundary in the integrated provirus and continues unidirectionally to produce genomic and mRNA products of positive polarity. Several studies have recently demonstrated the existence of naturally occurring protein-encoding transcripts of negative polarity in complex retroviruses. We report here on the identification of transcripts of negative polarity in simple murine leukemia virus (MLV). In T-cell and B-cell lymphomas induced by SL3-3 and Akv MLV, antisense transcripts initiated in the U3 region of the proviral 5′ long terminal repeat (LTR) and continued into the cellular proto-oncogenes Jdp2 and Bach2 to create chimeric transcripts consisting of viral and host sequence. The phenomenon was validated in vivo using a knock-in mouse model homozygous for a single LTR at a position known to activate Nras in B-cell lymphomas. A 5′ rapid amplification of cDNA ends (RACE) analysis indicated a broad spectrum of initiation sites within the U3 region of the 5′ LTR. Our data show for the first time transcriptional activity of negative polarity initiating in the U3 region of simple retroviruses and suggest a novel mechanism of insertional activation of host genes. Elucidation of the nature and potential regulatory role of 5′ LTR antisense transcription will be relevant to the design of therapeutic vectors and may contribute to the increasing recognition of pervasive eukaryotic transcription.

scholarly journals Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Xiangyu Zhang ◽  
Hailun Jiang ◽  
Wei Li ◽  
Jian Wang ◽  
Maosheng Cheng
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Active Sites ◽  
Tyrosine Phosphatase ◽  
Pharmacophore Model ◽  
Protein Tyrosine Phosphatase 1B ◽  
Binding Modes ◽  
Protein Tyrosine ◽  
R Region ◽  
Ptp1b Inhibitors ◽  
Autodock 4.0

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

scholarly journals Selective activation of a discrete family of endogenous proviral elements in normal BALB/c lymphocytes

1992 ◽  
Vol 12 (1) ◽  
pp. 220-228
Author(s):  
J A Mietz ◽  
J W Fewell ◽  
E L Kuff
Keyword(s):  
Normal Mouse ◽  
Methylation Status ◽  
Regulatory Region ◽  
Cell Types ◽  
Cdna Libraries ◽  
Cdna Clones ◽  
Sequence Specificity ◽  
Selective Activation ◽  
Mouse Tissues ◽  
R Region

Intracisternal A-particle (IAP) proviral elements are abundant and widely dispersed in the mouse genome. IAP-related transcripts have been detected in normal mouse tissues where expression is under genetic control. In this study, we sought to determine whether IAP expression in BALB/c thymus and lipopolysaccharide-stimulated B cells was due to selective or indiscriminate activation of IAP elements. cDNA libraries were prepared from each source. A total of 86 IAP cDNA clones were isolated from both libraries, and 37 of these were sequenced over a common 0.7- to 1.0-kb region of the IAP genome that included the 3' long terminal repeat (LTR). Three highly related families of elements were found to be expressed in the two cell types examined. All of the related elements had a distinctive U3 regulatory region. Thirteen individual IAP proviral elements were distinguished on the basis of sequence differences within the R region of the LTR. Hybridization of genomic DNA with element-specific oligonucleotide probes confirmed the presence of a restricted number of proviral copies in the lymphocyte-specific family of elements. Most of these copies were found to be methylated in the lymphocyte DNA, but at least seven were hypomethylated in their 5' LTRs. This study shows that activation of IAP elements in normal normal mouse lymphocytes is highly selective. Activation is probably a function of both sequence specificity and methylation status of the proviral LTR.

Transcriptional mapping of the amplified region encoding the dihydrofolate reductase-thymidylate synthase of Leishmania major reveals a high density of transcripts, including overlapping and antisense RNAs

1989 ◽  
Vol 9 (9) ◽  
pp. 3959-3972
Author(s):  
G M Kapler ◽  
S M Beverley
Keyword(s):  
Dihydrofolate Reductase ◽  
Thymidylate Synthase ◽  
Leishmania Major ◽  
Protozoan Parasite ◽  
Circular Dna ◽  
Antisense Rnas ◽  
Protein Levels ◽  
Polycistronic Transcription ◽  
Transcriptional Mapping ◽  
R Region

We have examined the transcriptional organization of the R region of the protozoan parasite Leishmania major. This region encodes the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) and is frequently amplified as a 30-kilobase (kb) extrachromosomal circular DNA in methotrexate-resistant lines. Northern (RNA) blot analysis shows that the R region encodes at least 10 stable cytoplasmic polysomal poly(A)+ RNAs, ranging in size from 1.7 to 13 kb and including the 3.2-kb DHFR-TS mRNA. Transcriptional mapping reveals that these RNAs are closely spaced and collectively cover more than 95% of the 30-kb amplified R region. The organization is complex, including several overlapping RNAs 3' of DHFR-TS and two examples of antisense RNAs 5' of DHFR-TS. The R region RNAs can be grouped into two empirical domains, with eight contiguous RNAs transcribed in the same direction as that of DHFR-TS and two contiguous RNAs transcribed in the orientation opposite to that of DHFR-TS. The two 5'-most RNAs of the DHFR-TS-containing domain overlap the RNAs transcribed from the opposite strand. These data are relevant to models of transcription, including recent studies suggesting polycistronic transcription in trypanosomatids. The abundance of R region RNAs increases uniformly 10- to 15-fold in the amplified R1000-3 line relative to the wild type, and no new RNAs were observed. This suggests that all elements required in cis for DHFR-TS expression are contained within the 30-kb circular DNA. Quantitative analysis reveals that the steady-state DHFR-TS mRNA and protein levels are not growth phase regulated, unlike the monofunctional mouse DHFR. DHFR-TS is developmentally regulated, however, declining about fivefold in lesion amastigotes relative to promastigotes.

scholarly journals The R Region Found in the Human Foamy Virus Long Terminal Repeat Is Critical for both Gag and Pol Protein Expression

2001 ◽  
Vol 75 (15) ◽  
pp. 6817-6824 ◽  
Author(s):  
Rebecca A. Russell ◽  
Yan Zeng ◽  
Otto Erlwein ◽  
Bryan R. Cullen ◽  
Myra O. McClure
Keyword(s):  
Protein Expression ◽  
Long Terminal Repeat ◽  
Splice Site ◽  
Foamy Virus ◽  
Noncoding Region ◽  
Terminal Repeat ◽  
Mrna Levels ◽  
Human Foamy Virus ◽  
Noncoding Sequence ◽  
R Region

ABSTRACT It has been suggested that sequences located within the 5′ noncoding region of human foamy virus (HFV) are critical for expression of the viral Gag and Pol structural proteins. Here, we identify a discrete ∼151-nucleotide sequence, located within the R region of the HFV long terminal repeat, that activates HFV Gag and Pol expression when present in the 5′ noncoding region but that is inactive when inverted or when placed in the 3′ noncoding region. Sequences that are critical for the expression of both Gag and Pol include not only the 5′ splice site positioned at +51 in the R region, which is used to generate the spliced pol mRNA, but also intronic R sequences located well 3′ to this splice site. Analysis of total cellular gag andpol mRNA expression demonstrates that deletion of the R region has little effect on gag mRNA levels but that R deletions that would be predicted to leave thepol 5′ splice site intact nevertheless inhibit the production of the spliced pol mRNA. Gag expression can be largely rescued by the introduction of an intron into the 5′ noncoding sequence in place of the R region but not by an intron or any one of several distinct retroviral nuclear RNA export sequences inserted into the mRNA 3′ noncoding sequence. Neither the R element nor the introduced 5′ intron markedly affects the cytoplasmic level of HFV gag mRNA. The poor translational utilization of these cytoplasmic mRNAs when the R region is not present incis also extended to a cat indicator gene linked to an internal ribosome entry site introduced into the 3′ noncoding region. Together these data imply that the HFV R region acts in the nucleus to modify the cytoplasmic fate of target HFV mRNA. The close similarity between the role of the HFV R region revealed in this study and previous data (M. Butsch, S. Hull, Y. Wang, T. M. Roberts, and K. Boris-Lawrie, J. Virol. 73:4847–4855, 1999) demonstrating a critical role for the R region in activating gene expression in the unrelated retrovirus spleen necrosis virus suggests that several distinct retrovirus families may utilize a common yet novel mechanism for the posttranscriptional activation of viral structural protein expression.

Risk analysis of multi-hazard in the Belt and Road region

2020 ◽  
Author(s):  
Danling Chai ◽  
Ming Wang ◽  
Kai Liu
Keyword(s):  
Central Africa ◽  
Temporal Distribution ◽  
Economic Loss ◽  
Disaster Risk ◽  
Seismic Zone ◽  
R Region ◽  
Belt And Road ◽  
High Level ◽  
The Belt And Road ◽  
Very High

<p>This paper focuses on the assessment of the multi-hazard natural disaster susceptibility and disaster risk in the Belt and Road (B&R) region. It is expected to provide a reference for cooperation in disaster risk reduction among B&R countries. Based on historical disaster data from 1980 to 2018, the disaster susceptibility of the B&R countries to multi-hazard has been analyzed using random forest model. The multi-hazard risk was further assessed based on the disaster susceptibility and Monte-Carlo method. Results show that regions with high susceptibility to meteorological hazards are mostly distributed in central Africa and the coastal areas of all continents. While Himalayan-Mediterranean seismic zone is susceptible to geological hazards. Due to the different distribution of regional exposures, the risks of economic loss and the risk of population casualties also appear differently. For economic loss risk, in grid scale very high and high level take 21% area. Europe, southeast China coast, and the Indian peninsula present higher economic loss risks. In population casualties risk, very high and high level take 15% area and in national scale the central and southern parts of Eurasia show higher population casualties risk. The results provide a comprehensive analysis of the spatial and temporal distribution, sensitivity, and disaster risk of natural disasters in B&R region, and provides a reference for regional disaster prevention and reduction cooperation.</p>

scholarly journals Effects of Homology Length in the Repeat Region on Minus-Strand DNA Transfer and Retroviral Replication

2001 ◽  
Vol 75 (2) ◽  
pp. 809-820 ◽  
Author(s):  
Que Dang ◽  
Wei-Shau Hu
Keyword(s):  
Reverse Transcription ◽  
Leukemia Virus ◽  
Dna Transfer ◽  
Full Length ◽  
Minus Strand ◽  
Rna Transcripts ◽  
R Region ◽  
Retroviral Replication ◽  
The Impact ◽  
Viral Titers

ABSTRACT Homology between the two repeat (R) regions in the retroviral genome mediates minus-strand DNA transfer during reverse transcription. We sought to define the effects of R homology lengths on minus-strand DNA transfer. We generated five murine leukemia virus (MLV)-based vectors that contained identical sequences but different lengths of the 3′ R (3, 6, 12, 24 and 69 nucleotides [nt]); 69 nt is the full-length MLV R. After one round of replication, viral titers from the vector with a full-length downstream R were compared with viral titers generated from the other four vectors with reduced R lengths. Viral titers generated from vectors with R lengths reduced to one-third (24 nt) or one-sixth (12 nt) that of the wild type were not significantly affected; however, viral titers generated from vectors with only 3- or 6-nt homology in the R region were significantly lower. Because expression and packaging of the RNA were similar among all the vectors, the differences in the viral titers most likely reflected the impact of the homology lengths on the efficiency of minus-strand DNA transfer. The molecular nature of minus-strand DNA transfer was characterized in 63 proviruses. Precise R-to-R transfer was observed in most proviruses generated from vectors with 12-, 24-, or 69-nt homology in R, whereas aberrant transfers were predominantly used to generate proviruses from vectors with 3- or 6-nt homology. Reverse transcription using RNA transcribed from an upstream promoter, termed read-in RNA transcripts, resulted in most of the aberrant transfers. These data demonstrate that minus-strand DNA transfer is homology driven and a minimum homology length is required for accurate and efficient minus-strand DNA transfer.

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