Draft ABA Model Surrogacy Act.
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Abortion, Induced↗
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Results for “Genetic Materials Act”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
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Virosomes as new carrier system for cancer vaccines.
HER-2/neu, a tumor-associated antigen (TAAg), plays a critical role in oncogenesis of various tumor types, and its selective overexpression by malignant tumor cells makes it an ideal target for immunotherapy. A prerequisite for clinical vaccines is the construction of safe and highly immunogenic reagents able to generate efficient immune responses against TAAg. Previous protein vaccines, consisting of the extracellular domain of HER-2/neu (pNeuECD), were shown to elicit an immune response that did not provide protection from transplantable tumors expressing HER-2/neu. Here we showed that virosomes, which consist of reconstituted viral envelopes without viral genetic material, can act as a carrier and an adjuvant for a truncated protein pNeuECD. Mice vaccinated with pNeuECD either encapsulated in virosomes or bound to the virosomal membrane (Vir-pNeuECD), generated rNeu-specific humoral and cytotoxic immune responses. In addition, Vir-p(NeuECD) induced significant tumor rejection and additionally did not lead to delayed tumor formation when compared with free pNeuECD in complete Freund's adjuvant. There was no difference between the virosomal constructs. Taken together these results suggest that virosomes, as clinically approved safe vaccines, can be used to elicit both humoral and cell-mediated responses against TAAg and induce tumor rejection. Our model is providing important preclinical data to design human vaccination trials for patients with tumors overexpressing HER-2/neu, either as a primary vaccination or as a boost in combination with other vaccines in a context of an adjuvant treatment plan.
Animals↗
Effect of growth in lithium on ouabain binding, Na-K-ATPase and Na and K transport in hela cells.
1. HeLa cells were grown for 24 hr in growth medium in which part of the Na was replaced with Li. Ion contents, cell volumes and numbers, Na-K-ATPase and specific ouabain binding were measured. In some experiments the Na efflux and net Na transport was also measured. 2. Growth in Li caused a rise in the specific ouabain binding and membrane Na-K-ATPase of these cells. The Li concentrations in the cells necessary to produce this effect ranged up to 50 mM. 3. It is suggested that Li, like Na, acts on the genetic material of the cells to cause the production of more Na pumps within the membrane.
Adenosine Triphosphatases↗
Conferring a federal property right in genetic material: stepping into the future with the Genetic Privacy Act.
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Cell Line↗
Gene duplication and other evolutionary strategies: from the RNA world to the future.
Beginning with a hypothetical RNA world, it is apparent that many evolutionary transitions led to the complexity of extant species. The duplication of genetic material is rooted in the RNA world. One of two major routes of gene amplification, retroposition, originated from mechanisms that facilitated the transition to DNA as hereditary material. Even in modern genomes the process of retroposition leads to genetic novelties including the duplication of protein and RNA coding genes, as well as regulatory elements and their juxtapositon. We examine whether and to what extent known evolutionary principles can be applied to an RNA-based world. We conclude that the major basic Neo-Darwinian principles that include amplification, variation and selection already governed evolution in the RNA and RNP worlds. In this hypothetical RNA world there were few restrictions on the exchange of genetic material and principles that acted as borders at later stages, such as Weismann's Barrier, the Central Dogma of Molecular Biology, or the Darwinian Threshold were absent or rudimentary. RNA was more than a gene: it had a dual role harboring, genotypic and phenotypic capabilities, often in the same molecule. Nuons, any discrete nucleic acid sequences, were selected on an individual basis as well as in groups. The performance and success of an individual nuon was markedly dependent on the type of other nuons in a given cell. In the RNA world the transition may already have begun towards the linkage of nuons to yield a composite linear RNA genome, an arrangement necessitating the origin of RNA processing. A concatenated genome may have curbed unlimited exchange of genetic material; concomitantly, selfish nuons were more difficult to purge. A linked genome may also have constituted the beginning of the phenotype/genotype separation. This division of tasks was expanded when templated protein biosynthesis led to the RNP world, and more so when DNA took over as genetic material. The aforementioned barriers and thresholds increased and the significance and extent of horizontal gene transfer fluctuated over major evolutionary transitions. At the dawn of the most recent transformation, a fast evolutionary transition that we will be witnessing in our life times, a form of Lamarckism is raising its head.
Animals↗
The Hox Paradox: More complex(es) than imagined.
An understanding of the origin of different body plans requires knowledge of how the genes and genetic pathways that control embryonic development have evolved. The Hox genes provide an appealing starting point for such studies because they play a well-understood causal role in the regionalization of the body plan of all bilaterally symmetric animals. Vertebrate evolution has been characterized by gene, and possibly genome, duplication events, which are believed to have provided raw genetic material for selection to act upon. It has recently been established that the Hox gene organization of ray-finned fishes, such as the zebrafish, differs dramatically from that of their lobe-finned relatives, a group that includes humans and all the other widely used vertebrate model systems. This unusual Hox gene organization of zebrafish is the result of a duplication event within the ray-finned fish lineage. Thus, teleosts, such as zebrafish, have more Hox genes arrayed over more clusters (or "complexes") than do tetrapod vertebrates. Here, I review our understanding of Hox cluster architecture in different vertebrates and consider the implications of gene duplication for Hox gene regulation and function and the evolution of different body plans.
Animals↗
The interaction of host immunocompetence and tumor aggressiveness in superficial bladder carcinoma.
The results of our studies suggest that in the natural history of bladder cancer intrinsic tumor aggressiveness as measured by loss of normal antigenic activity may be more relevant than intact host defenses as measured by an intact cell-mediated immune response. Our contention that tumor aggressiveness may be the more important variable fits in with the occasional success in cancer patients treated with chemotherapeutic agents that act by altering the genetic material of rapidly dividing tumor cells. Our data suggest that therapy directed at bolstering the host's immune system may not be as effective as therapy directed against molecular events within the cancer cells themselves. Unfortunately, presently available non-surgical modalities do not discriminate between aggressor (tumor) and defender (lymphocyte) cells.
Antibody Formation↗
Sister chromatid exchanges and chromosome aberrations induced by radiosensitizing agents in bone marrow cells of treated tumor-bearing mice.
The frequency of sister chromatid exchanges (SCE) in vivo and chromosome aberrations and/or alterations were analyzed from the bone marrow cells of the treated dbrB tumor-bearing DBA/1J inbred mouse host. The results were compared with analogous data obtained from the bone marrow cells of untreated tumor-bearing mice for evaluation of the "indirect," i.e., somatic stress, effect on the normal host cells following triple-agent therapy intended for a mammary adenocarcinoma. Misonidazole (MIS), which is a known radiosensitizing drug, microwave hyperthermia (delta), and X-radiation (X) were used as therapeutic agents. Significant (P less than 0.05) numbers of SCE were induced in the bone marrow cells of the mice whose tumors received these triple-agent treatments (MIS + delta + X) simultaneously as compared with values of SCE per cell noted in bone marrow cells of untreated tumor-bearing control mice. The highest number of chromosome aberrations and alterations, including an increase in heteroploidy, was also noticed in the bone marrow cells of the mice whose tumors were treated simultaneously with MIS + delta + X. The triple-agent therapy on dbrB tumor also resulted in an unusually high polyploid metaphase plate in the bone marrow cell consisting of 320 chromosomes, indicating that this mode of therapy may act directly on the genetic material of the tumor-bearing host cells, inducing cytogenetic abnormalities as a side effect.
Animals↗
Hormonal steroids act as tumour promoters by modulating oncogene expression.
Recent advances in the molecular action of steroid hormones and in the role of oncogenes in cell transformation are considered in defining, at the molecular level, the involvement of steroid hormones in tumour formation. In the context of the generally accepted three-stage model of carcinogenesis, it is proposed that the hormonal steroids act as tumour promoters by modulating oncogene expression. It is postulated that the hormonal steroids act on cells in which the initiating carcinogen has either induced mutations in protooncogenes normally hormonally regulated or has induced changes in gene architecture, aligning protooncogenes to hormone-responsive elements, thus placing these genes under non-physiological hormonal control. In contrast to the defined action of solitary carcinogens on the genetic material, tumour promoters appear to act by various molecular pathways, one of which, as hypothesized for hormonal steroids, could be a direct effect on oncogene expression.
Base Sequence↗
The fates of zebrafish Hox gene duplicates.
In his 1970 book, Susumu Ohno stressed the importance of gene duplication in the evolution of the vertebrate genome and body plan. He elaborated the idea that duplication events provide novel genetic material on which evolution may act. Data are accumulating to show that extensive duplication events, perhaps incorporating the duplication of entire genomes, occurred in the lineage leading to teleost fishes. These duplications may have been pivotal in the explosive radiation of this highly successful vertebrate group. Thus, the teleosts provide us with an ideal opportunity to investigate the fates and functions of duplicated genes. A convenient system for these studies is the zebrafish, Danio rerio, which has become a popular genetic and embryological model.
Animals↗
Identification of a region in the herpes simplex virus scaffolding protein required for interaction with the portal.
The herpes simplex virus type 1 capsid is a protective shell that acts as a container for the genetic material of the virus. After assembly of the capsid, the viral DNA is translocated into the capsid interior through a channel formed by the portal. The portal is composed of a dodecamer of UL6 molecules which form a ring-like structure found at a single vertex within the icosahedron. Formation of portal-containing capsids minimally requires the four structural proteins (VP5, VP19C, VP23, and UL6) and a scaffolding protein (UL26.5). Recently, an interaction between UL26.5 and the portal has been identified, suggesting the scaffold functions by delivering the portal to the growing capsid shell. The aim of this study was to identify regions within UL26.5 required for its interaction with the portal. A specific region was identified by mutational analysis. Deletion of scaffold amino acids (aa) 143 to 151 was found to be sufficient to inhibit formation of the scaffold-portal complex as assayed in vitro. The aa 143 to 151 contain the sequence YYPGE, which is highly conserved among alpha herpesviruses. Although it did not bind to the portal, the Delta143-151 mutant was found to retain the ability to support assembly of morphologically normal capsids in vitro. Such capsids, however, did not contain the portal. The results suggest assembly of portal-containing capsids requires formation of a scaffold-portal complex in which intermolecular contact is dependent on scaffold aa 143 to 151.
Amino Acid Sequence↗
Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. What is the role of genome duplication in the evolution of complexity and diversity?
Gene and genome duplications provide a source of genetic material for mutation, drift, and selection to act upon, making new evolutionary opportunities possible. As a result, many have argued that genome duplication is a dominant factor in the evolution of complexity and diversity. However, a clear correlation between a genome duplication event and increased complexity and diversity is not apparent, and there are inconsistencies in the patterns of diversity invoked to support this claim. Interestingly, several estimates of genome duplication events in vertebrates are preceded by multiple extinct lineages, resulting in preduplication gaps in extant taxa. Here we argue that gen(om)e duplication could contribute to reduced risk of extinction via functional redundancy, mutational robustness, increased rates of evolution, and adaptation. The timeline for these processes to unfold would not predict immediate increases in species diversity after the duplication event. Rather, reduced probabilities of extinction would predict a latent period between a genome duplication and its effect on species diversity or complexity. In this paper, we will develop the idea that genome duplication could contribute to species diversity through reduced probability of extinction.
Animals↗
Chiral DNA packaging in DNA-cationic liposome assemblies.
Recent studies have indicated that the structural features of DNA-lipid assemblies, dictated by the lipid composition and cationic lipid-to-DNA ratio, critically affect the efficiency of these complexes in acting as vehicles for cellular delivery of genetic material. Using circular dichroism we find that upon binding DNA, positively-charged liposomes induce a secondary conformational transition of the DNA molecules from the native B form to the C motif. Liposomes composed of positively-charged and neutral 'helper' lipids, found to be particularly effective as transfecting agents, induce - in addition to secondary conformational changes - DNA condensation into a left-handed cholesteric-like phase. A structural model is presented according to which two distinct, yet inter-related modes of DNA packaging coexist within such assemblies. The results underline the notion that subtle changes in the components of a supramolecular assembly may substantially modulate the interplay of interactions which dictate its structure and functional properties.
Cations↗
Characteristics of current international trade of live salmonid eggs.
World trade in live salmonid embryos (eyed eggs) has grown in response to increased global salmon production, particularly in South America, and parallels international trade in farmed salmonid products. Rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar) and coho salmon (O. kisutch) are the most commercially important species. In 1992, the Food and Agriculture Organization of the United Nations estimated world production of rainbow trout at 300,000 tonnes, while the production of Atlantic salmon was estimated at 250,000 tonnes and coho salmon at 50,000 tonnes. One can estimate that roughly 3 billion, 150 million and 30 million eggs, respectively, were required to produce this yield. Broodstock are cultivated world-wide, using a wide variety of water sources, including the marine environment, riverine water containing anadromous fish, and ground water free of migrating fish. As many as 70% of all coho eggs are derived from feral fish. Approximately 50% of all commercial salmonid eyed eggs are produced in Europe, and approximately 15% are produced in the state of Washington, United States of America. Conditions which are ideal for commercial salmonid grow-out are not necessarily ideal for the cultivation of salmonid broodstock; this is one reason why international egg trade is necessary. The trend of current salmonid health regulations is towards facilitating egg commerce on a regional level, in an attempt to control disease transmission. Regulations controlling egg importation often include pathogens which are not vertically transmitted. This serves only to increase egg prices, in compensation for the cost of laboratory tests. Genetic improvements have been the cornerstone of increasing commercial production of all agricultural commodities. Fish health regulations are sometimes instituted in an effort to protect the local industry, but in fact they act more often to restrict the flow of genetic material and may actually serve to reduce industry productivity and profitability.
Africa↗
Genetically modified maize and soybean on the Egyptian food market.
The results of a survey study on food samples produced from genetically modified soybean and maize collected from the Egyptian market are presented. Forty samples of soybean and 40 samples of maize products have been gathered randomly from markets in Cairo and Giza. The genetic modification was detected by polymerase chain reaction (PCR) using official detection methods according to section 35 of the German Foodstuffs Act. Samples were investigated for the presence of material derived from the following genetically modified organisms (GMOs) all of which are approved for food use in Europe: Roundup Ready soybean (RRS) and maize lines Bt176, Bt11, T25 and MON810. In addition, samples were examined in qualitative and quantitative analysis for the presence of material derived from the transgenic maize line StarLink (Aventis) which was approved for animal feed use exclusively in the US. Twenty % of 40 investigated soy samples contained Roundup Ready soybean; 15% of 40 maize samples tested positive for Bt176 and 12.5% positive for Bt11 maize. Furthermore, the presence of StarLink maize could clearly be demonstrated in four samples mixed with Bt176 and Bt11. The percentage of StarLink was less than 1% in quantitative analysis. The maize lines T25 and MON810 were not detected.
DNA, Plant↗
A review of alcohol clearance in humans.
The level of blood or brain alcohol is considered to influence alcohol ingestion by causing subjective perceptions or neural activations that are reinforcing or rewarding. Alcohol-dependent people may try to maintain some desired tissue level, drinking to replace the millimolar levels that were cleared from the blood by metabolism. The biomedical literature describes many approaches to understanding the role of blood alcohol levels in human physiology and behavior, and this review examines some of the published results. They include the general kinetics of intake and removal of beverage alcohol as well as the characteristics of many different catalysts that can interact with alcohol. Because ingested alcohol creates blood levels that are a 1000-fold greater than those normally experienced during abstinence, ethanol may impose itself as an alternate substrate for the many oxidoreductases that act physiologically on other endogenous alcohols. Many enzymes that can act on millimolar ethanol have been isolated, and their structural genes are sequenced. Unfortunately, the genetic sequence does not indicate the physiological material upon which the translated gene product may act. In a sense, the set of enzymes with catalytic sites occupied by millimolar ethanol during alcohol drinking might constructively be regarded as "orphan gene products" whose physiological role remains to be clarified. This review is designed to indicate some of what is known, what is not known, and what needs to be known to improve the interpretations regarding adaptations to beverage alcohol and the ability of millimolar levels of alcohol to diminish dysphoria. The dysphoria may be influenced by ethanol, by ethanol metabolites, or by altered metabolism of currently unspecified endogenous substrates. A major challenge is to evaluate the multiple alternative variables within a context that stimulates curiosity and encourages quantitative tests of the relative contribution of each variable to the overall physiology of an individual.
Alcohol Dehydrogenase↗
NIDDK data repository: a central collection of clinical trial data.
BACKGROUND: The National Institute of Diabetes and Digestive and Kidney Diseases have established central repositories for the collection of DNA, biological samples, and clinical data to be catalogued at a single site. Here we present an overview of the site which stores the clinical data and links to biospecimens. DESCRIPTION: The NIDDK Data repository is a web-enabled resource cataloguing clinical trial data and supporting information from NIDDK supported studies. The Data Repository allows for the co-location of multiple electronic datasets that were created as part of clinical investigations. The Data Repository does not serve the role of a Data Coordinating Center, but rather as a warehouse for the clinical findings once the trials have been completed. Because both biological and genetic samples are collected from many of the studies, a data management system for the cataloguing and retrieval of samples was developed. CONCLUSION: The Data Repository provides a unique resource for researchers in the clinical areas supported by NIDDK. In addition to providing a warehouse of data, Data Repository staff work with the users to educate them on the datasets as well as assist them in the acquisition of multiple data sets for cross-study analysis. Unlike the majority of biological databases, the Data Repository acts both as a catalogue for data, biosamples, and genetic materials and as a central processing point for the requests for all biospecimens. Due to regulations on the use of clinical data, the ultimate release of that data is governed under NIDDK data release policies. The Data Repository serves as the conduit for such requests.
Access to Information↗
cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.
The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation.
Avian Sarcoma Viruses↗