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At least 1,207 records · Page 67Linked to original sources
PubMed1994

Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus.

Genetic variation of the more complex retroviruses in the human T-cell leukemia virus/bovine leukemia virus (HTLV/BLV) group is less than in some other retroviral genera. To test whether reverse transcription of HTLV/BLV group members is less error prone than that of members of other groups, we developed an assay for detecting forward mutations in BLV, similar to that developed for the simpler spleen necrosis virus (SNV). We used this system to study the rates and types of mutations that occur during a single replication cycle. We found that BLV reverse transcription is approximately two and one-half times less error prone than SNV reverse transcription (4.8 x 10(-6) versus 1.2 x 10(-5) mutation per bp per cycle, respectively). The relative numbers of all types of observed mutations (that is, base pair substitutions, frameshifts, deletions, and deletions with insertions) were similar for BLV and SNV.

Animals↗
PubMed2006

A microsatellite-based consensus linkage map for species of Eucalyptus and a novel set of 230 microsatellite markers for the genus.

BACKGROUND: Eucalypts are the most widely planted hardwood trees in the world occupying globally more than 18 million hectares as an important source of carbon neutral renewable energy and raw material for pulp, paper and solid wood. Quantitative Trait Loci (QTLs) in Eucalyptus have been localized on pedigree-specific RAPD or AFLP maps seriously limiting the value of such QTL mapping efforts for molecular breeding. The availability of a genus-wide genetic map with transferable microsatellite markers has become a must for the effective advancement of genomic undertakings. This report describes the development of a novel set of 230 EMBRA microsatellites, the construction of the first comprehensive microsatellite-based consensus linkage map for Eucalyptus and the consolidation of existing linkage information for other microsatellites and candidate genes mapped in other species of the genus. RESULTS: The consensus map covers approximately 90% of the recombining genome of Eucalyptus, involves 234 mapped EMBRA loci on 11 linkage groups, an observed length of 1,568 cM and a mean distance between markers of 8.4 cM. A compilation of all microsatellite linkage information published in Eucalyptus allowed us to establish the homology among linkage groups between this consensus map and other maps published for E. globulus. Comparative mapping analyses also resulted in the linkage group assignment of other 41 microsatellites derived from other Eucalyptus species as well as candidate genes and QTLs for wood and flowering traits published in the literature. This report significantly increases the availability of microsatellite markers and mapping information for species of Eucalyptus and corroborates the high conservation of microsatellite flanking sequences and locus ordering between species of the genus. CONCLUSION: This work represents an important step forward for Eucalyptus comparative genomics, opening stimulating perspectives for evolutionary studies and molecular breeding applications. The generalized use of an increasingly larger set of interspecific transferable markers and consensus mapping information, will allow faster and more detailed investigations of QTL synteny among species, validation of expression-QTL across variable genetic backgrounds and positioning of a growing number of candidate genes co-localized with QTLs, to be tested in association mapping experiments.

Alleles↗
PubMed2005

[Genetic analysis of the predisposition to audiogenic seizure fits in Krushinsky-Molodkina rat strain].

The expression of audiogenic seizure fits has been studied in F1 hybrids between audiogenic seizure-prone Krushinsky-Molodkina rat strain and Wistar rats not prone to audiogenic seizures, as well as in two backcross generations. Only 10% of F1 hybrids exhibit audiogenic seizure fits, whereas the frequency of this character in two generations of their backcrosses with Krushinsky-Molodkina rats is about 50%. A digenic model with incomplete penetrance has been put forward to explain the control of audiogenic seizure fits. This model fits the data obtained: the theoretically expected distributions of the character in offsprings of different crosses do not differ significantly from those observed in experiments. The model explains why the distribution of the character is the same in the first and second backcross offsprings.

Animals↗
PubMed2007

Applications of transcriptional profiling in antibiotics discovery and development.

This chapter will review specific applications of microarray technology and related data analysis strategies in antibacterial research and development. We present examples of microarray applications spanning the entire antibiotics research and development pipeline, from target discovery, assay development, pharmacological evaluation, to compound safety studies. This review emphasizes the utility of microarrays for a systematic evaluation of novel chemistry as antibiotic agents. Transcriptional profiling has revolutionized the process of target elucidation and has the potential to offer substantial guidance in the identification of new targets. Microarrays will continue to be a workhorse of anti-infectives discovery programs ranging from efficacy assessments of antibiotics ('forward pharmacology') to drug safety evaluations ('toxicogenomics').

Anti-Bacterial Agents↗
PubMed1991

Cystic fibrosis--the way forward from the gene.

Cloning of the cystic fibrosis (CF) gene and elucidation of the physiological functions of the encoded protein is a triumph, not only for molecular biology, but also for people affected by CF. For them, not only is there now the possibility of screening for the commonest mutations, but they may also look forward to the prospect of improved therapies being developed.

Animals↗
PubMed2004

Platelet monoamine oxidase, personality and alcoholism: the rise, fall and resurrection.

The history of research on the association between platelet monoamine oxidase (MAO) activity and personality traits, such as sensation seeking and impulsiveness, is reviewed. The effects of MAO-inhibiting compounds in cigarette smoke for the interpretation of this association are discussed. Recent results confirming a true association between platelet MAO activity and personality are presented. From a clinical point of view, this association has had its greatest impact on the understanding of the nature of constitutional factors making individuals vulnerable for e.g. substance abuse and the link between low platelet MAO activity and type 2 alcoholism, recently confirmed on non-human primates, is discussed. The molecular mechanisms underlying the association between platelet MAO and behaviour are discussed and evidence that common transcriptional factors, e.g. within the AP-2 family, regulating both the expression of platelet MAO and components of central monoaminergic systems, such as synthetizing enzymes, receptors and transporters, are presented. A hypothesis is put forward, that such common transcription factors may not directly regulate platelet MAO expression, but rather mitochondrial number or outer membrane surface.

Alcoholism↗
PubMed2004

Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin.

BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. METHODS: In a cohort of 204 (62% males) ESRD patients aged 52 +/- 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2 years) and gender-matched (64% males) healthy subjects served as control subjects. RESULTS: Markedly (P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 microg/mL), especially type 1 diabetic patients (36.8 microg/mL), compared to control subjects (12.2 microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P < 0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral fat mass (P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene -11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype. CONCLUSION: The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD.

Adiponectin↗
PubMed1999

The golden decade of molecular floral development (1990-1999): A cheerful obituary

Cloning of genes involved in the specification of floral meristem and organ identity and in the transition to flowering in some model plants such as Arabidopsis, Antirrhinum, and Petunia during the last decade represents an unprecedented step forward towards an understanding of floral development. Most of these genes belong to conserved and widespread gene families encoding transcription factors, such as the MADS-box genes, FLO-like, and AP2-like genes. Current work on the molecular genetic basis of floral development still focuses on a deeper understanding of the classical model systems, which are all higher eudicots. However, in order to apply the current knowledge about floral developmental genetics to plant breeding and evolutionary biology, flowering plant diversity is now also seriously taken into account. In the next decade, developmental control genes will be studied less and less individually, but rather as components of complex gene regulatory networks. The necessary technology is currently being developed. Learning to understand the origin and evolution of these gene networks will also help to clarify the origin and diversification of flowers, one of the most "abominable" and long-standing mysteries of botany. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗
PubMed1978

[Rhodosporidium Banno: dose-effect relations, mutagenic efficiency, and spectrum of mutants in the induction of auxotrophic mutants by ultraviolet light and N-methyl-N'-nitro-N-nitrosoguanidine].

The kinetics, efficiency, and specificity of induction of forward mutations to auxotrophy by ultraviolet light (UV) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in stationary phase cells of Rhodosporidium (Rhodotorula) wild strain Rg1. In comparison to the spontaneous level the frequency of auxotrophic mutants was increased more than 1000 times by both mutagens, however, the mutagenic efficiency of MNNG was higher than that of UV. We found that the forward mutation rate is a linear function of the applicated UV and MNNG doses in the range to 600 J m-2 or 25 mM X min, respectively. The 35 studied biosynthetic pathways to amino acids, purines, pyrimidines, and vitamins are genetically blocked at different frequencies, but there is not any significant difference between UV and MNNG induced frequencies of mutants with a specific requirement. However, in difference to the approximately equal distribution of the MNNG-induced nic mutants among the genetic blocks of the tryptophan-nicotinamide pathway, UV-induced nic mutants occurred with a higher frequency in the genes of the tryptophan pyrrolase and the 3-hydroxykynureninase than in the genes of the other enzymes of the pathway.

Amino Acids↗
PubMed2001

The use of sector field ICP-mass spectrometry for Rb-Sr geochronological dating.

Rb-Sr dating, one of the most important tools in geochronology, requires determination of the Rb/Sr concentration ratios and the 87Sr/86Sr isotope ratios in co-genetic minerals or rocks and is traditionally performed by thermal ionization mass spectrometry (TIMS). In this work we investigated whether sector field inductively coupled plasma mass spectrometry (ICP-MS), which is characterized by a high sample throughput and straight-forward sample introduction, could be used as an alternative to TIMS. To avoid spectral overlap of the ion signals of the isobaric nuclides 87Sr and 87Rb, Sr was separated from Rb by cation-exchange chromatography. A mathematical correction was applied to take into account the small amount of Rb that can be present in the Sr fraction. The isotope ratio accuracy and precision attainable with ICP-MS were evaluated by analysis of several reference materials from the US Geological Survey. The results of this evaluation show that excellent accuracy could be achieved; the internal precision (repeatability) of the isotope ratio (expressed as the relative standard deviation for 10 successive 1-min measurements) was 0.04-0.12%. An attempt was made to calculate the total or combined uncertainty on the isotope ratio results, by also taking into account other possible error sources (corrections for mass discrimination, detector dead time, blank signal and Rb fraction). Finally, the same procedure was used for dating two rock formations that were 2,500 Ma and 350 Ma old, according to age determinations previously performed by the Rb-Sr laboratory of the University of München (Germany) using TIMS. The ICP-MS results (2,520 +/- 150 Ma and 379 +/- 48 Ma) obtained for these formations compare well with the corresponding TIMS data (2,509 +/- 120 Ma and 357 +/- 25 Ma).

Journal Article↗
PubMed2002

Therapeutic developments in the treatment of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterised by the selective death of motor neurones. The mechanisms and processes responsible for the selective loss of motor neurones are still unknown, however several hypotheses have been put forward, including oxidative damage and/or toxicity from intracellular aggregates due to mutant superoxide dismutase-1 activity, axonal strangulation from cytoskeletal abnormalities, loss of trophic factor support and glutamate-mediated excitotoxicity. These theories are based on a better understanding of the genetics of amyotrophic lateral sclerosis and on biochemical and pathological analysis of post-mortem tissue. They have led to the development of appropriate animal and cell culture models, allowing the sequence of events in motor neuronal degeneration to be unravelled and potential therapeutic agents to be screened. Unfortunately, the majority of therapeutics found to be efficacious in the animal and cell culture models have failed in human trials. Riluzole is still the only proven therapy in humans, shown to extend survival of amyotrophic lateral sclerosis patients by approximately 3 months, but it has no effect on muscle strength. Other potential therapeutic approaches are being identified, including inhibition of caspase-mediated cell death, maintenance of mitochondrial integrity and energy production, regulation of glutamate homeostasis, reduction of inflammation and control of neurofilament synthesis. Hopefully, in the near future some new agents will be found that can alter the course of this devastating and fatal disease.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Detection of differentially expressed genes in HeLa x fibroblast hybrids using subtractive suppression hybridization.

To understand genetic differences and similarities between tumorigenic and nontumorigenic HeLa x fibroblast hybrid cells, subtractive suppression hybridization (SSH), based on suppression PCR and a combination of normalization and subtraction in a single procedure, was used. Using the nontumorigenic CGL1 and tumorigenic CGL3, forward (CGL1-CGL3) and reverse (CGL3-CGL1) subtracted libraries were constructed. Among 192 clones, seven were identified as differentially expressed genes specific for either CGL1 or CGL3. All seven were not reported previously as differentially expressed genes in this hybrid system. In the forward subtraction, p16 was isolated, indicating the involvement of the loss of tumorigenic phenotype. Subsequent transfection of wild-type p16 to the tumorigenic CGL3 showed growth suppression in colony formation assay; however, no tumor suppression was observed when the transfectant was inoculated into nude mice. These results indicate that: (a) SSH is a suitable method to identify differentially expressed genes in two types of cells; and (b) although p16 plays some roles in growth suppression, the p16-transfected CGL3 is still capable to proliferate in vivo.

Animals↗
PubMed2002

Inheritance and fine mapping of fertility restoration for cytoplasmic male sterility in Gossypium hirsutum L.

Genetics of CMS fertility restoration was presented through the analysis of classic genetics and molecular markers. Based on F(2) segregation of the crosses between CMS and the restoring lines, the testcrosses and F(1) x F(1) populations, together with RAPD and SSR mapping, one dominant gene was identified to control the CMS fertility restoration in cotton. The strategy of genotype representation analysis (GRA) was put forward to screen the markers linked with the Rf(1) locus. Using 1,025 random decamer primers and 282 pairs of SSR primers, two RAPD and three SSR markers were identified to be closely linked to the Rf(1) gene. Among the five markers, three were co-dominantly inherited. Additionally, based on the analysis of monosomic and telesomic lines with one SSR maker, the Rf(1) locus could be located on the long arm of chromosome 4. The molecular markers available here are helpful in the development of the elite restoring lines in cotton by marker-assisted selection.

Chromosome Mapping↗
PubMed2005

Altered nuclear transfer: a way forward for embryonic stem cell research.

The present conflict over the moral status of the human embryo reflects deep differences in our basic convictions and is unlikely to be resolved through deliberation or debate. While there are currently no federally legislated constraints on the use of private funds for this research, there is a consensus opinion in the scientific community that without NIH support for newly created embryonic stem cell lines, progress in this important realm of research will be severely constrained. A May, 2005, report by the President's Council on Bioethics, "Alternative Sources of Pluripotent Stem Cells," outlines several proposals for obtaining pluripotent stem cells without the destruction of human embryos. One of these methods, Altered Nuclear Transfer, proposes to use the technology of somatic cell nuclear transfer (SCNT), but with a preemptive genetic or epigenetic alteration that precludes the integrated and coordinated organization essential for natural embryogenesis. Drawing on insights from systems biology, the distinction between totipotency (capacity to form a whole organism) and pluripotency (capacity to form all the cell types) is explored. The implications of this distinction are used to discuss the moral arguments for the inviolability of nascent human life and the moral standing of entities with only partial and unorganized developmental potential. Away forward is proposed that may open positive avenues of advance in both stem cell research and a broader arena of research in developmental biology.

Bioethical Issues↗
PubMed1996

Absence of mutagenic effects of sodium dichloroacetate.

Sodium dichloroacetate (DCA) is a drug with potential for treating patients with stroke and head injury. Conflicting evidence has been published on the mutagenic potential of DCA. A series of genetic tests for mutagenicity and clastogenicity was carried out on pharmaceutical grade DCA. Four types of mutagenicity test were included, with and without metabolic activation where appropriate. These studies included: (i) Salmonella and Escherichia coli mutation (Ames) test, (ii) thymidine kinase locus forward mutation in L5178Y mouse lymphoma cells, (iii) tests for chromosomal aberrations in Chinese hamster ovary cells, and (iv) and in vivo rat bone marrow erythroid micronucleus test. In each study, there was no evidence of mutagenic activity attributable to DCA. It is possible that the present test material, of pharmaceutical grade, has fewer impurities than materials studied in previous reports. These data extend, and in some cases contradict, previous published reports on DCA.

Animals↗