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At least 145 records · Page 8Linked to original sources
PubMed2024

One-pot Golden Gate Assembly of an avian infectious bronchitis virus reverse genetics system.

Avian infectious bronchitis is an acute respiratory disease of poultry of particular concern for global food security. Investigation of infectious bronchitis virus (IBV), the causative agent of avian infectious bronchitis, via reverse genetics enables deeper understanding of virus biology and a rapid response to emerging variants. Classic methods of reverse genetics for IBV can be time consuming, rely on recombination for the introduction of mutations, and, depending on the system, can be subject to genome instability and unreliable success rates. In this study, we have applied data-optimized Golden Gate Assembly design to create a rapidly executable, flexible, and faithful reverse genetics system for IBV. The IBV genome was divided into 12 fragments at high-fidelity fusion site breakpoints. All fragments were synthetically produced and propagated in E. coli plasmids, amenable to standard molecular biology techniques for DNA manipulation. The assembly can be carried out in a single reaction, with the products used directly in subsequent viral rescue steps. We demonstrate the use of this system for generation of point mutants and gene replacements. This Golden Gate Assembly-based reverse genetics system will enable rapid response to emerging variants of IBV, particularly important to vaccine development for controlling spread within poultry populations.

Infectious bronchitis virus↗
PubMed2005

An improved reverse genetics system for influenza A virus generation and its implications for vaccine production.

The generation of vaccines for highly pathogenic avian influenza viruses, including those of the H5N1 subtype, relies on reverse genetics, which allows the production of influenza viruses from cloned cDNA. In the future, reverse genetics will likely be the method of choice for the generation of conventional influenza vaccine strains because gene reassortment by more traditional methods is cumbersome. Established systems for the artificial generation of influenza A viruses require transfection of cells with the eight to 12 plasmids that provide the eight influenza viral RNAs as well as the polymerase and nucleoproteins of the virus. However, cell lines appropriate for human vaccine production (e.g., Vero cells) cannot be transfected with high efficiencies. To overcome these problems, we established a reverse genetics system in which the eight RNA polymerase I transcription cassettes for viral RNA synthesis are combined on one plasmid. Similarly, two cassettes encoding the hemagglutinin and neuraminidase segments and six cassettes encoding the remaining proteins were combined. We also combined three RNA polymerase II transcription cassettes for the expression of the polymerase subunits. By combining these cassettes, we reduced the number of plasmids required for virus generation significantly and produced influenza A virus in Vero cells with higher efficiency than with the traditional 12 plasmid system. This new system is thus suitable for influenza virus vaccine production and may be applicable to other reverse genetics systems that rely on the introduction of several plasmids into eukaryotic cells.

Animals↗
PubMed1982

Biological responsiveness to the phorbol esters and specific binding of [3H]phorbol 12,13-dibutyrate in the nematode Caenorhabditis elegans, a manipulable genetic system.

Because of its suitability for genetic studies, the nematode Caenorhabditis elegans was examined for its responsiveness to the phorbol esters. Phorbol 12-myristate 13-acetate had three effects. It inhibited the increase in animal size during growth; it decreased the yield of progeny; and it caused uncoordinated movement of the adult. The effects on nematode size, progeny yield, and movement were quantitated. Concentrations of phorbol 12-myristate 13-acetate yielding half-maximal responses were 440, 460, and 170 nM, respectively. As was expected from the biological responsiveness of the nematodes, specific, saturable binding of phorbol ester to nematode extracts was found. [3H]phorbol 12,13-dibutyrate bound with a dissociation constant of 26.8 +/- 3.9 nM. At saturation, 5.7 +/- 1.4 pmole/mg protein was bound.

Animals↗
PubMed1990

Assembly of the cricket cercal sensory system: genetic and epigenetic control.

The cercal sensory system of the cricket is being examined using anatomical, physiological, and computer simulation techniques in order to better understand the assembly of sensory systems. This particular sensory system is of interest because it functions like numerically more complex vertebrate sensory systems but offers, to the neuroscientist, the technical advantages of a small number of large identified neurons. Two aspects of sensory processing are being examined in this system; the spatial aspects of a stimulus that tell an animal where a target is in its environment, and the qualities of a stimulus that help the animal to identify the stimulus. The spatial aspects of a stimulus are analyzed by a topographic mapping of the animal's sensory environment. The feature extraction machinery for other aspects of the stimulus lacks any obvious anatomical order and is embedded within the topographic map. We are attempting to tease apart the genetic and the epigenetic components of the assembly process for this sensory system. Here we review our progress with emphasis on the epigenetic aspects of its assembly. We describe previously published work on plasticity as well as new experiments focussed on the role of neuronal activity in the assembly of this neural circuit. Finally, we briefly describe simulation experiments that are helping us understand the role of various forms of synaptic plasticity in the determination of receptive fields.

Animals↗
PubMed1988

AIDS: no association with the genetic systems GC (D-binding protein), ORM (orosomucoid = alpha-1-acid glycoprotein), and A2HS (alpha-2-HS-glycoprotein).

In a sample of 97 HIV-1 seropositive persons which comprised 34 patients with AIDS, 30 patients with persistent generalized lymphadenopathy or with AIDS related complex and 33 persons who were without symptoms and called "healthy", three genetic marker systems were examined: 1) GC, the group-specific component of serum which is identical with the vitamin D binding protein (DBP) of serum, 2) ORM, the acute phase protein orosomucoid = alpha-1-acid glycoprotein of serum, and 3) A2HS, the alpha-2-AS glycoprotein of serum. The distribution of the genotypes and of the alleles in the sample of AIDS patients and of HIV-1/positive persons was not different from the distribution in control groups. An association between susceptibility and/or resistance for AIDS and these genetic marker systems was not observed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A computer system for analysis and integrated description of regulation of the molecular-genetic system of interferon induction and action.

A new theoretical approach to elaboration of an information-analytical integrated knowledge base containing data on regulation and function of biological systems is presented. The knowledge base incorporates: (i) a reference database containing experimental data on the structural-functional organization of a biological system; (ii) a dynamic mathematical model for analysis of the evolution of the system over time; and (iii) an interpretation module of simulation results. Application of this approach to theoretical investigation of the interferon system in the case of viral infection is discussed. The approach is specific in that it uses mathematical modeling technology, which allows one to generate mathematical models of different degrees of complexity in the analysis of the diverse aspects of biological system behavior. This approach allows one not only to store and to treat available experimental data, but also to acquire new knowledge about the behavior of a biological system. The proposed approach is implemented as a computer system for the IBM PC and compatibles.

Algorithms↗
PubMed1998

Shortcomings of current genetic evaluation systems.

Genetic evaluation, as the term is used today in the beef cattle and sheep industries, refers to the calculation and dissemination of genetic predictions for individual traits. If genetic predictions are to be used wisely, however, genetic evaluation should be broadened to include multiple-trait selection technology, preferably technology that is customized for individual commercial and seedstock producers. Most of the recent research in the area of genetic prediction/multiple-trait selection has focused on the use of economic selection indexes that incorporate genetic predictions produced within breeds. This approach is complicated by genotype x genotype, genotype x environment, and more complex interactions, and the changing correlations they create. The use of a mechanistic technology, bioeconomic simulation, to calculate economic weights can avoid some of the problems caused by interactions, but to implement this technology, academic animal breeders must accept the mechanistic concept of genetic potential and devise ways to translate current within-breed genetic predictions to predictions of this new measure. Sire selection by simulation, a multiple-trait selection technology described in detail in this article, uses bioeconomic simulation in a way that offers advantages over traditional selection indexes in terms of both functionality and appeal. For any customized technology to be applied on a meaningful scale, research priorities must change, and the business relationships between research groups and animal breeding industries must be restructured.

Animals↗
PubMed2001

[Renin-angiotensin system genetic polymorphisms and essential hypertension in the Spanish population].

BACKGROUND: The goal of this study was to analyse the association between essential hypertension and the main genetic polymorphisms at the renin-angiotensin system in the Spanish population. PATIENTS AND METHOD: Case-control study including 185 essential hypertensive subjects(age [SD] 39.6 [7.5] years, 52% women, systolic blood pressure 151.2 [17.4] mmHg, diastolic blood pressure 96.0 [9.4] mmHg) and 350 sex- and age-matched normotensive individuals selected from a sample of the general population of the Comunidad Valenciana, Spain (age 39.4 [8.0] years, 51.7% women, systolic blood pressure 116.0 [12.0] mmHg, diastolic blood pressure 69.6 [8.5] mmHg). A PCR was performed to determine I/D angiotensin converting enzyme (ACE) gene polymorphism, A-6G and M235T angiotensinogen gene polymorphism and A1166C polymorphism of the angiotensin II type 1 receptor. RESULTS: There were no differences between cases and controls with regard to genotypic and allelic distributions. In hypertensive patients,there were no differences in genotypic or allelic distributions after considering the presence or absence of a familial history of hypertension or comparing tertiles of systolic and diastolic blood pressure values. Only in women, the combination of a C allele of A1166C polymorphism with an A-6G angiotensinogen polymorphism A allele (p = 0.007), or an M235T angiotensinogen polymorphism T allele (p = 0.007), was associated with a higher risk of hypertension. CONCLUSIONS: We found no association between essential hypertension risk and I/D ACE gene, M235T and A-6G angiotensinogen gene, or A1166C angiotensin II type 1 receptor gene polymorphisms. An epistatic effect was observed in young women between angiotensin II type 1 receptor polymorphisms and angiotensinogen polymorphisms.

Adolescent↗
PubMed2004

Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening.

Larval zebrafish are used extensively for developmental genetic studies due to their salient features, such as small size, external development, optical transparency, and accessibility in large numbers. However, their use for the study of drug and alcohol abuse has not been explored. Here we investigated the response of larval zebrafish to acute treatment of alcohol. Our analyses showed that like adults, the larval zebrafish exhibited a dose-dependent locomotor response to ethanol: intermediate doses led to hyperactivity, whereas high doses have a neurodepressive effect resulting in hypoactivity and sedation. Alcohol also induced morphological changes of melanocytes, providing a visible cellular measure of the biological effects of alcohol in vivo. In addition, alcohol induced thigmotaxis behavior (preference for the edge of a compartment). In the behaviors we analyzed, genetic background influenced the locomotor responses to alcohol. The present study demonstrates that larval zebrafish exert a response to the acute treatment of alcohol, which is genetically modifiable. Therefore, the larval zebrafish represent a tractable vertebrate model system for a large-scale genetic analysis of the biological effects of alcohol.

Animals↗
PubMed2002

A somatic cell genetic system for dissecting hemopoietic cytokine signal transduction.

Somatic cell genetics has proven to be a powerful tool for the dissection of cytokine signal transduction pathways. Here we describe a system in which interleukin-6 (IL-6) signaling may be dissected using myeloid leukemic M1 cells. We utilized two properties of M1 cell differentiation to isolate IL-6-unresponsive mutants. First, M1 differentiation is associated with cessation of cell division. Second, differentiated M1 cells migrate rapidly and form dispersed colonies in agar. Mutant clones that are unresponsive to IL-6 are, therefore, large and compact as compared with clones derived from IL-6-responsive wild type M1 cells. Following spontaneous or chemically induced mutagenesis and selection in a high dose of IL-6, we isolated 27 M1 clones unresponsive to IL-6. Three harbored mutations that acted in a dominant manner, whereas 24 contained recessive mutations. gp130, an IL-6 receptor component, was affected in many mutant clones. We show that these clones display IL-6 and leukemia inhibitory factor receptors with reduced binding affinities and express gp130 at reduced levels. The IL-6-unresponsive phenotype of these mutant clones was fully rescued by the transfection of exogenous gp130 DNA. Therefore, this approach targets components of the IL-6 signaling pathway and may be suitable to study signaling from a variety of cytokines.

Animals↗
PubMed1995

[The prospect of studying genetic systems using an informational-logical approach].

A new information technology, the information-logical approach (ILA), which is based on information theory methods and the fuzzy sets theory, is considered. This method can be applied for the majority of biological and ecological studies, and in genetics. In breeding and genetic studies, ILA can be used as a basis for the development of methods that will allow one to take into account ecological, geographic, climatic, and other peculiarities of trait expression that influence productivity. Application of ILA also opens new prospects for analyzing results of genetic and ecological monitoring (e.g., post-Chernobyl' monitoring) to predict further behavior of the systems studied. This paper presents a general outline of information analysis, describes a block of one-factor analysis, which was implemented on a personal computer and has a user-friendly interface, and also presents several examples concerning application of ILA to specific genetic systems.

Environmental Monitoring↗
PubMed1973

The genetic system in parthenogenetic strains of Drosophila mercatorum.

Five parthenogenetic laboratory strains of Drosophila mercatorum have been examined for their mode of diploidization in the eggs of females. Diploidization occurs either by pronuclear duplication leading to complete homozygosity or by nuclear fusion. If the latter occurs between pronuclei from different secondary oocytes, heterozygosity can be maintained. Each of the five strains shows some nuclear fusion and three show significantly different amounts, ranging from about 21% to less than 1%. Even in strains with a strong tendency towards homozygosity, it is argued that this dual system of nuclear reconstitution provides for genetic recombination; thus, the strains retain considerable evolutionary potential.

Animals↗
PubMed1998

A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo.

A detection system for interactions between membrane proteins in vivo is described. The system is based on split-ubiquitin [Johnsson, N. & Varshavsky, A. (1994) Proc. Natl. Acad. Sci. USA 91, 10340-10344]. Interaction between two membrane proteins is detected by proteolytic cleavage of a protein fusion. The cleavage releases a transcription factor, which activates reporter genes in the nucleus. As a result, interaction between membrane proteins can be analyzed by the means of a colorimetric assay. We use membrane proteins of the endoplasmic reticulum as a model system. Wbp1p and Ost1p are both subunits of the oligosaccharyl transferase membrane protein complex. The Alg5 protein also localizes to the membrane of the endoplasmic reticulum, but does not interact with the oligosaccharyltransferase. Specific interactions are detected between Wbp1p and Ost1p, but not between Wbp1p and Alg5p. The new system might be useful as a genetic and biochemical tool for the analysis of interactions between membrane proteins in vivo.

Cloning, Molecular↗
PubMed2000

Insect population control using a dominant, repressible, lethal genetic system.

A major modification to the sterile insect technique is described, in which transgenic insects homozygous for a dominant, repressible, female-specific lethal gene system are used. We demonstrate two methods that give the required genetic characteristics in an otherwise wild-type genetic background. The first system uses a sex-specific promoter or enhancer to drive the expression of a repressible transcription factor, which in turn controls the expression of a toxic gene product. The second system uses non-sex-specific expression of the repressible transcription factor to regulate a selectively lethal gene product. Both methods work efficiently in Drosophila melanogaster, and we expect these principles to be widely applicable to more economically important organisms.

Animals↗
PubMed2001

Development of a genetic system for the transfer of DNA into Flavobacterium heparinum.

Flavobacterium heparinum (now Pedobacter heparinus) is a Gram-negative soil bacterium which can produce yellow pigments. It synthesizes five enzymes that degrade glycosoaminoglycan molecules. The study of this unique bacterium has been limited by the absence of a genetic manipulation system. In this paper, the construction of a conjugation/integration plasmid system and a broad-host-range plasmid, both of which contain a F. heparinum functional selective marker created by placing the trimethoprim resistance gene, dhfrII, under the control of the hepA regulatory region is described. Both plasmids were introduced into F. heparinum by conjugation and/or electroporation, and trimethoprim resistant colonies were obtained. Fifty electroporants were obtained per microgram covalently closed circular plasmid DNA. The existence of integrated plasmid DNA was confirmed by Southern hybridization and PCR. The existence of a derivative of the broad-host-range plasmid pBBR1 in F. heparinum was demonstrated by plasmid digestion and Southern hybridization, and by transformation of Escherichia coli.

Blotting, Southern↗