The Functional Psychoses – Are Oncogenes Involved in Their Pathogenesis? Some Speculations

1991 ◽  
Vol 158 (4) ◽  
pp. 563-568 ◽  
Author(s):  
John Leach
Keyword(s):  
Tissue Culture ◽  
Dna Sequences ◽  
Complementary Dna ◽  
Viral Oncogenes ◽  
The Past ◽  
Wide Range ◽  
Functional Psychoses ◽  
Neoplastic Change ◽  
Eukaryotic Organisms

Oncogenes are genes whose expression has been associated with malignant transformation of cells in tissue culture and with neoplastic change in vivo (Bishop, 1987). Much of the current understanding of their nature and action has stemmed from work, over the past 20 years, on tumour viruses (Temin, 1971; Rapp, 1983). One group of tumour viruses, the retroviruses, are unique in possessing an enzyme, reverse transcriptase, which transcribes to the cell DNA a copy of the viral RNA genome (Marks, 1987). After the discovery of viral oncogenes, such DNA copies were used as probes in hybridisation studies (Stehelin et al, 1976; Frankel & Fischinger, 1976). These probes, capable of annealing to complementary DNA sequences, revealed the existence of the latter in normal, unaffected cells (Willecke & Schäfer, 1984). These sequences, called cellular or proto-oncogenes, exist in a wide range of eukaryotic organisms, from yeast to man.

scholarly journals In vitro analysis of a transcription termination site for RNA polymerase II.

1990 ◽  
Vol 10 (11) ◽  
pp. 5782-5795 ◽  
Author(s):  
D K Wiest ◽  
D K Hawley
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Dna Sequences ◽  
Nuclear Extract ◽  
Transcription Unit ◽  
Dependent Manner ◽  
Wide Range ◽  
Vitro Analysis

Transcription from the adenovirus major late (ML) promoter has previously been shown to pause or terminate prematurely in vivo and in vitro at a site within the first intron of the major late transcription unit. We are studying the mechanism of elongation arrest at this site in vitro to define the DNA sequences and proteins that determine the elongation behavior of RNA polymerase II. Our assay system consists of a nuclear extract prepared from cultured human cells. With standard reaction conditions, termination is not observed downstream of the ML promoter. However, in the presence of Sarkosyl, up to 80% of the transcripts terminate 186 nucleotides downstream of the start site. Using this assay, we showed that the DNA sequences required to promote maximal levels of termination downstream of the ML promoter reside within a 65-base-pair region and function in an orientation-dependent manner. To test whether elongation complexes from the ML promoter were functionally homogeneous, we determined the termination efficiency at each of two termination sites placed in tandem. We found that the behavior of the elongation complexes was different at these sites, with termination being greater at the downstream site over a wide range of Sarkosyl concentrations. This result ruled out a model in which the polymerases that read through the first site were stably modified to antiterminate. We also demonstrated that the ability of the elongation complexes to respond to the ML termination site was promoter specific, as the site did not function efficiently downstream of a heterologous promoter. Taken together, the results presented here are not consistent with the simplest class of models that have been proposed previously for the mechanism of Sarkosyl-induced termination.

scholarly journals Recent Developments in Liposome-Based Veterinary Therapeutics

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hassan Sadozai ◽  
Dorsa Saeidi
Keyword(s):  
Veterinary Medicine ◽  
Research Interest ◽  
Circulation Time ◽  
Phospholipid Vesicles ◽  
Future Directions ◽  
Ongoing Research ◽  
The Past ◽  
Wide Range ◽  
Recent Developments

Recent advances in nanomedicine have been studied in the veterinary field and have found a wide variety of applications. The past decade has witnessed a massive surge of research interest in liposomes for delivery of therapeutic substances in animals. Liposomes are nanosized phospholipid vesicles that can serve as delivery platforms for a wide range of substances. Liposomes are easily formulated, highly modifiable, and easily administered delivery platforms. They are biodegradable and nontoxic and have long in vivo circulation time. This review focuses on recent and ongoing research that may have relevance for veterinary medicine. By examining the recent developments in liposome-based therapeutics in animal cancers, vaccines, and analgesia, this review depicts the current significance and future directions of liposome-based delivery in veterinary medicine.

scholarly journals VIRMOTIF: A User-Friendly Tool for Viral Sequence Analysis

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 186
Author(s):  
Pedram Rajaei ◽  
Khadijeh Hoda Jahanian ◽  
Amin Beheshti ◽  
Shahab S. Band ◽  
Abdollah Dehzangi ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Mean Shift ◽  
Virus Genome ◽  
Viral Sequence ◽  
The Past ◽  
Performance Diagnosis ◽  
Wide Range ◽  
Clustering Data ◽  
User Friendly ◽  
Tools And Methods

Bioinformatics and computational biology have significantly contributed to the generation of vast and important knowledge that can lead to great improvements and advancements in biology and its related fields. Over the past three decades, a wide range of tools and methods have been developed and proposed to enhance performance, diagnosis, and throughput while maintaining feasibility and convenience for users. Here, we propose a new user-friendly comprehensive tool called VIRMOTIF to analyze DNA sequences. VIRMOTIF brings different tools together as one package so that users can perform their analysis as a whole and in one place. VIRMOTIF is able to complete different tasks, including computing the number or probability of motifs appearing in DNA sequences, visualizing data using the matplotlib and heatmap libraries, and clustering data using four different methods, namely K-means, PCA, Mean Shift, and ClusterMap. VIRMOTIF is the only tool with the ability to analyze genomic motifs based on their frequency and representation (D-ratio) in a virus genome.

scholarly journals Jump around: transposons in and out of the laboratory

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 135
Author(s):  
Anuj Kumar
Keyword(s):  
Transposable Elements ◽  
Dna Sequences ◽  
Major Constituent ◽  
Mobile Dna ◽  
Mutagenic Potential ◽  
Complex Interactions ◽  
Wide Range ◽  
Transposon Insertions ◽  
The Impact

Since Barbara McClintock’s groundbreaking discovery of mobile DNA sequences some 70 years ago, transposable elements have come to be recognized as important mutagenic agents impacting genome composition, genome evolution, and human health. Transposable elements are a major constituent of prokaryotic and eukaryotic genomes, and the transposition mechanisms enabling transposon proliferation over evolutionary time remain engaging topics for study, suggesting complex interactions with the host, both antagonistic and mutualistic. The impact of transposition is profound, as over 100 human heritable diseases have been attributed to transposon insertions. Transposition can be highly mutagenic, perturbing genome integrity and gene expression in a wide range of organisms. This mutagenic potential has been exploited in the laboratory, where transposons have long been utilized for phenotypic screening and the generation of defined mutant libraries. More recently, barcoding applications and methods for RNA-directed transposition are being used towards new phenotypic screens and studies relevant for gene therapy. Thus, transposable elements are significant in affecting biology both in vivo and in the laboratory, and this review will survey advances in understanding the biological role of transposons and relevant laboratory applications of these powerful molecular tools.

scholarly journals In Silico Estimation of the Abundance and Phylogenetic Significance of the Composite Oct4-Sox2 Binding Motifs within a Wide Range of Species

Data ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. 111
Author(s):  
Arman Kulyyassov ◽  
Ruslan Kalendar
Keyword(s):  
High Throughput ◽  
Dna Sequences ◽  
High Throughput Sequencing ◽  
Regulatory Elements ◽  
Scoring Method ◽  
Sequencing Technologies ◽  
Wide Range ◽  
Multiple Species ◽  
Eukaryotic Organisms ◽  
The Impact

High-throughput sequencing technologies have greatly accelerated the progress of genomics, transcriptomics, and metagenomics. Currently, a large amount of genomic data from various organisms is being generated, the volume of which is increasing every year. Therefore, the development of methods that allow the rapid search and analysis of DNA sequences is urgent. Here, we present a novel motif-based high-throughput sequence scoring method that generates genome information. We found and identified Utf1-like, Fgf4-like, and Hoxb1-like motifs, which are cis-regulatory elements for the pluripotency transcription factors Sox2 and Oct4 within the genomes of different eukaryotic organisms. The genome-wide analysis of these motifs was performed to understand the impact of their diversification on mammalian genome evolution. Utf1-like, Fgf4-like, and Hoxb1-like motif diversity was evaluated across genomes from multiple species.

In vitro analysis of a transcription termination site for RNA polymerase II

1990 ◽  
Vol 10 (11) ◽  
pp. 5782-5795
Author(s):  
D K Wiest ◽  
D K Hawley
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Dna Sequences ◽  
Nuclear Extract ◽  
Transcription Unit ◽  
Dependent Manner ◽  
Wide Range ◽  
Vitro Analysis

Transcription from the adenovirus major late (ML) promoter has previously been shown to pause or terminate prematurely in vivo and in vitro at a site within the first intron of the major late transcription unit. We are studying the mechanism of elongation arrest at this site in vitro to define the DNA sequences and proteins that determine the elongation behavior of RNA polymerase II. Our assay system consists of a nuclear extract prepared from cultured human cells. With standard reaction conditions, termination is not observed downstream of the ML promoter. However, in the presence of Sarkosyl, up to 80% of the transcripts terminate 186 nucleotides downstream of the start site. Using this assay, we showed that the DNA sequences required to promote maximal levels of termination downstream of the ML promoter reside within a 65-base-pair region and function in an orientation-dependent manner. To test whether elongation complexes from the ML promoter were functionally homogeneous, we determined the termination efficiency at each of two termination sites placed in tandem. We found that the behavior of the elongation complexes was different at these sites, with termination being greater at the downstream site over a wide range of Sarkosyl concentrations. This result ruled out a model in which the polymerases that read through the first site were stably modified to antiterminate. We also demonstrated that the ability of the elongation complexes to respond to the ML termination site was promoter specific, as the site did not function efficiently downstream of a heterologous promoter. Taken together, the results presented here are not consistent with the simplest class of models that have been proposed previously for the mechanism of Sarkosyl-induced termination.

scholarly journals Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes

2019 ◽  
Vol 35 (1) ◽  
pp. 357-379 ◽  
Author(s):  
Judith F. Kribelbauer ◽  
Chaitanya Rastogi ◽  
Harmen J. Bussemaker ◽  
Richard S. Mann
Keyword(s):  
Conceptual Understanding ◽  
Dna Sequences ◽  
Binding Sites ◽  
Cell Biology ◽  
Affinity Binding ◽  
Eukaryotic Transcription ◽  
Wide Range ◽  
Dna Binding Affinity ◽  
Factor Specificity

Eukaryotic transcription factors (TFs) from the same structural family tend to bind similar DNA sequences, despite the ability of these TFs to execute distinct functions in vivo. The cell partly resolves this specificity paradox through combinatorial strategies and the use of low-affinity binding sites, which are better able to distinguish between similar TFs. However, because these sites have low affinity, it is challenging to understand how TFs recognize them in vivo. Here, we summarize recent findings and technological advancements that allow for the quantification and mechanistic interpretation of TF recognition across a wide range of affinities. We propose a model that integrates insights from the fields of genetics and cell biology to provide further conceptual understanding of TF binding specificity. We argue that in eukaryotes, target specificity is driven by an inhomogeneous 3D nuclear distribution of TFs and by variation in DNA binding affinity such that locally elevated TF concentration allows low-affinity binding sites to be functional.

scholarly journals Dynamic Physiological Culture of Ex Vivo Human Tissue: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2870
Author(s):  
Daniel Ll Hughes ◽  
Aron Hughes ◽  
Zahir Soonawalla ◽  
Somnath Mukherjee ◽  
Eric O’Neill
Keyword(s):  
Systematic Review ◽  
Tissue Culture ◽  
Human Tissue ◽  
Ex Vivo ◽  
Self Regulation ◽  
Success Rates ◽  
Diverse Range ◽  
Wide Range ◽  
The Creation

Conventional static culture fails to replicate the physiological conditions that exist in vivo. Recent advances in biomedical engineering have resulted in the creation of novel dynamic culturing systems that permit the recapitulation of normal physiological processes ex vivo. Whilst the physiological benefit for its use in the culture of two-dimensional cellular monolayer has been validated, its role in the context of primary human tissue culture has yet to be determined. This systematic review identified 22 articles that combined dynamic physiological culture techniques with primary human tissue culture. The most frequent method described (55%) utilised dynamic perfusion culture. A diverse range of primary human tissue was successfully cultured. The median duration of successful ex vivo culture of primary human tissue for all articles was eight days; however, a wide range was noted (5 h–60 days). Six articles (27%) reported successful culture of primary human tissue for greater than 20 days. This review illustrates the physiological benefit of combining dynamic culture with primary human tissue culture in both long-term culture success rates and preservation of native functionality of the tissue ex vivo. Further research efforts should focus on developing precise biochemical sensors that would allow for real-time monitoring and automated self-regulation of the culture system in order to maintain homeostasis. Combining these techniques allows the creation of an accurate system that can be used to gain a greater understanding of human physiology.

Optical Properties of HVEM Accelerators

1975 ◽  
Vol 33 ◽  
pp. 180-181
Author(s):  
A. Strojnik ◽  
J.W. Scholl ◽  
V. Bevc
Keyword(s):  
Optical Properties ◽  
Electron Accelerator ◽  
Systematic Investigation ◽  
Electron Source ◽  
High Brightness ◽  
The Past ◽  
Wide Range ◽  
Optical Behavior

The electron accelerator, as inserted between the electron source (injector) and the imaging column of the HVEM, is usually a strong lens and should be optimized in order to ensure high brightness over a wide range of accelerating voltages and illuminating conditions. This is especially true in the case of the STEM where the brightness directly determines the highest resolution attainable. In the past, the optical behavior of accelerators was usually determined for a particular configuration. During the development of the accelerator for the Arizona 1 MEV STEM, systematic investigation was made of the major optical properties for a variety of electrode configurations, number of stages N, accelerating voltages, 1 and 10 MEV, and a range of injection voltages ϕ0 = 1, 3, 10, 30, 100, 300 kV).

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

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