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PubMedDate not supplied

[Low-molecular-weight RNA of eukaryotes: biogenesis, subcellular localization, functions].

The experimental data on the organization and expression of the low-molecular-weight RNA genes on the subcellular localization, metabolism and evolution of these RNA are summarized. The processes in which they are involved are discussed. The biological role of the low-molecular-weight RNA is paid a special attention. A hypothesis concerning the involvement of these molecules in the mechanism of active transport of proteins from the cytoplasm into the nucleus of the cell is put forward.

Animals↗
PubMed1975

[Effect of actinomycin D on transformation of the planulae of Obelia loveni (Allman)].

The incubation of planulae Obelia loveni in the actinomycin D solution (40 mug/ml) for 3 hrs at 17--20 degrees resulted in the marked inhibition of the process of attachment of planulae to the substrate and their transformation in polyps. A suggestion is put forward that at the final phase of larval development a special RNA is synthesized which participates in the genetically determined control of the complicated morphogenetic phenomenon of attachment and transformation of the planula in polyp.

Animals↗
PubMed2006

A real-time RT-PCR assay for quantifying the fitness of tobacco etch virus in competition experiments.

Relative fitness determination has become a standard tool in experimental virus evolution studies. In this type of studies, the tested strain is mixed with a reference strain, which differs in an easy-to-score and genetically stable marker, and allowed to compete for a limited common pool of resources during a given number of generations. In this report, a TaqMan real-time PCR methodology is proposed for quantifying the relative fitness of tobacco etch potyvirus strains (TEV) in in planta mixed infections with a reference TEV strain. Two different forward primers along with a common reverse one are used into separated reactions mixes from the same RNA preparation. The reference strain, named TEV-PC1, was genetically engineered to carry a neutral marker in a highly conserved region of the RNA polymerase NIb gene. This marker allows tracking the frequency of both competitors during competition experiments by real-time quantitative PCR using specific primers. Both the reproducibility and sensitivity of the method have been explored. Reproducibility was assessed by running multiple competition experiments for the same genotype. Sensitivity was assessed by comparing the results of competition experiments against TEV-PC1 of 24 single-nucleotide substitutions mutants.

Gene Amplification↗
PubMed2002

Asthma: the importance of epithelial mesenchymal communication in pathogenesis. Inflammation and the airway epithelium in asthma.

Asthma is a disorder of the airways in which Th-2-mediated inflammation is considered to provide the basis for altered structure and function that leads to bronchial hyper-responsiveness (BHR) and variable airflow obstruction. This linear progression underpinning asthma pathophysiology is questioned on the basis of observations on the pathology of the disease in early childhood, the independent genetic factors that influence atopy and BHR, incomplete responses to treatment with corticosteroids despite powerful anti-inflammatory effects and the recent disappointing results with targeted therapies that almost abolish eosinophilia in the blood and airways and yet produce little effect on the clinical outcomes of asthma. An alternative hypothesis is put forward in which atopy/airway inflammation and altered structure and function of the formed airway elements are parallel but interacting factors. For asthma to develop as a chronic disease, genetic and environmental factors that drive each of these components are required. Fundamental to this is the concept of aberrant signalling between the airway epithelium and underlying mesenchyme and persistent activation of the epithelial mesenchymal trophic unit.

Asthma↗
PubMed2000

Characterization of mutations induced by ethyl methanesulfonate, UV, and trimethylpsoralen in the nematode Caenorhabditis elegans.

The genome project of the nematode Caenorhabditis elegans is completed. It is important and useful to disrupt nematode genes to know their function. We treated wild-type animals with potential candidates for mutagens for reverse genetics, EMS (ethyl methanesulfonate), short-wavelength UV, and long-wavelength UV in the presence of TMP (trimethylpsoralen). We estimated forward mutation rates by counting the occurrence of a marker unc-22 mutation. We found that the forward mutation rate by TMP/UV could be comparable with EMS by improving the frequency one order higher than before. We next isolated mutants of another marker gene ben-1 and examined the probability for the deletion mutations by PCR and sequencing. Deletion mutations were found only by TMP/UV method, which suggested TMP/UV is the choice for deletion mutagenesis among these methods. As a pilot experiment, we could isolate actual deletion mutations at a much higher frequency than previously.

Animals↗
PubMed2026

Causal relationships between oral-gut microbiome and bone neoplasm-related phenotypes: Insights from bidirectional Mendelian randomization.

The human oral and gut microbiota are the 4 largest microbial communities in the body and play crucial roles in maintaining homeostasis and influencing disease. Observational studies have suggested links between these microbiota and bone neoplasm-related phenotypes, but establishing causality has been challenging due to confounding factors and reverse causality. We conducted a bidirectional, 2-sample Mendelian randomization (MR) study to investigate evidence consistent with a potential causal association between the saliva and gut microbiota and various bone neoplasm-related phenotypes. Genetic instruments for saliva and gut microbiota were sourced from large genome-wide association studies. Inverse variance weighted was the primary MR method, supplemented by 4 other MR techniques. Sensitivity analyses, including MR-Egger regression, were performed to assess pleiotropy and heterogeneity. In the forward MR analysis, Veillonella parvula from the saliva microbiota was associated with a decreased risk of bone and connective tissue neoplasms (β: -0.236, 95% CI: [-0.275, -0.197], P = 8.20E-33). MR analyses identified genetically predicted associations between several microbial taxa and bone neoplasm-related phenotypes. Reverse MR analyses showed that genetic liability to bone neoplasm-related phenotypes was associated with variation in the composition of the oral (e.g., Order Bacteroidales, Rothia mucilaginosa) and gut microbiota (e.g., Class Methanobacteria, Genus Eubacterium oxidoreducens group). Sensitivity analyses confirmed the robustness of these findings, as no statistical evidence of substantial heterogeneity or directional horizontal pleiotropy was detected. This study provides genetic evidence supporting a bidirectional causal relationship between specific saliva and gut microbiota and bone neoplasm-related phenotypes. Our findings identify several microbial taxa as potential candidates for future biomarker development and therapeutic investigation in bone neoplasm-related phenotypes. However, these genetically informed associations require further mechanistic, experimental, and prospective clinical validation before clinical application.

Humans↗
PubMed2006

The quest for genetic determinants of human longevity: challenges and insights.

Twin studies show that genetic differences account for about a quarter of the variance in adult human lifespan. Common polymorphisms that have a modest effect on lifespan have been identified in one gene, APOE, providing hope that other genetic determinants can be uncovered. However, although variants with substantial beneficial effects have been proposed to exist and several candidates have been put forward, their effects have yet to be confirmed. Human studies of longevity face numerous theoretical and logistical challenges, as the determinants of lifespan are extraordinarily complex. However, large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress.

Alleles↗
PubMed2005

N-ethyl-N-nitrosourea mutagenesis: boarding the mouse mutant express.

In the mouse, random mutagenesis with N-ethyl-N-nitrosourea (ENU) has been used since the 1970s in forward mutagenesis screens. However, only in the last decade has ENU mutagenesis been harnessed to generate a myriad of new mouse mutations in large-scale genetic screens and focused, smaller efforts. The development of additional genetic tools, such as balancer chromosomes, refinements in genetic mapping strategies, and evolution of specialized assays, has allowed these screens to achieve new levels of sophistication. The impressive productivity of these screens has led to a deluge of mouse mutants that wait to be harnessed. Here the basic large- and small-scale strategies are described, as are the basics of screen design. Finally, and importantly, this review describes the mechanisms by which such mutants may be accessed now and in the future. Thus, this review should serve both as an overview of the power of forward mutagenesis in the mouse and as a resource for those interested in developing their own screens, adding onto existing efforts, or obtaining specific mouse mutants that have already been generated.

Alkylating Agents↗
PubMed1997

Human molecular genetics research at the International Centre for Genetic Engineering and Biotechnology.

The ICGEB started its activity in 1987 as a special project of UNIDO (United Nations Industrial Development Organization) and operates now as a fully autonomous International Organization, of which 40 countries are members at present. The mandate of ICGEB is to become a Centre of excellence for research and training in modern biology addressed to the needs of the developing world. The ICGEB consists of two main laboratories, one in Trieste (where the direction of the Centre is also located) and one in New Delhi, plus a network of 30 Affiliated Centres. The Centre operates through: 1) specific research programs of hish scientific content at the Trieste and New Delhi laboratories; 2) long term training through post-doctoral and pre-doctoral fellowships; 3) short term training; 4) collaborative research program, through which the Centre finances research projects of major impact to the need of the Member States; 5) scientific services, namely consultation for scientific programs, distribution of reagents and a bioinformatics network particularly geared to the human genome research. The research on human molecular genetics in particularly active in the Trieste Component and concerns the study at the molecular level of several genes important for human health: control of DNA replication, response to infectious diseases, cardiocirculatory diseases, cystic fibrosis and cancer. The methodologies for developing new diagnostic methods and for developing gene therapy protocols are actively pursued. Through these programs, the member countries have access to state-of-the-art technologies anf know-how essential for the development of the molecular approaches to medicine brought forward by the study of the human genome.

Biotechnology↗
PubMed2003

Two decades of research on etiology and genetic factors in the abdominal aortic aneurysm (AAA)--with a glimpse into the 21st century.

Long gone are the days when the question of "etiology" of the abdominal aortic aneurysm (AAA) required a simplistic response. AAA is caused by an interplay of environmental and genetic factors, each of which may modify the expression of the other. A low penetrance, an insidious onset, and a wide distribution have forced scientists to rely on complex approaches to elucidate the pathophysiology of AAA. Hypotheses over the last twenty years have evaluated several components of connective tissue structure, function, and regulation. Although there has been considerable overlap in the many genetic approaches undertaken to explain aneurysm development, research recently has focused on reverse-engineering techniques. While earlier investigations using a "forward" or "candidate gene approach" have provided many insights in the understanding of AAA disease, advances in statistical modeling, new techniques in molecular biology, and gross computing power have now made more feasible the development of a reverse approach. New hope lies with the development of biochemical and computing tools which have paralleled information's vast dissemination in this rapidly widening field. Aortic inflammation and the upregulation of proteases and dysfunctional tissue-turnover are receiving more attention. No doubt, the interplay of all of these technologies will occupy investigators with an interest in AAA etiology for many years to come.

Aortic Aneurysm, Abdominal↗
PubMed1992

Protective effect of two sunscreens against lethal and genotoxic effects of UVB in V79 Chinese hamster cells and Saccharomyces cerevisiae strains XV185-14C and D5.

Effects of p-aminobenzoic acid (PABA) and of 4-[(2-oxo-3-bornylidene)methyl]-phenyl trimethylammonium methylsulfate (OMM), two components used in sunscreen formulations, on the mutagenicity of UVB irradiation are compared in three genetic assay systems. A haploid strain of Saccharomyces cerevisiae XV185-14C was used to measure reverse mutations at three loci. The diploid strain D5 of Saccharomyces cerevisiae was used to screen for reciprocal mitotic recombination. The induction of forward mutations was measured in Chinese hamster V79 cells. Our results indicate that UVB irradiation induced HGPRT- mutants in V79 cells, reverse mutations in Saccharomyces cerevisiae strain XV185-14C, and mitotic crossing over and other genetic alterations in Saccharomyces cerevisiae strain D5. V79 Chinese hamster lung cells were the most sensitive to UVB irradiation, followed by Saccharomyces cerevisiae haploid strain XV185-14C and the diploid strain D5. PABA and OMM were both capable of protecting all three types of cells from UVB irradiation regarding both lethality and induction of various types of genetic alterations. At higher concentrations (above 10(-5) M), OMM was more effective in its photoprotective effect toward UVB irradiation than PABA.

4-Aminobenzoic Acid↗
PubMed2005

The new look of behavioral genetics in developmental psychopathology: gene-environment interplay in antisocial behaviors.

This article reviews behavioral-genetic research to show how it can help address questions of causation in developmental psychopathology. The article focuses on studies of antisocial behavior, because these have been leading the way in investigating environmental as well as genetic influences on psychopathology. First, the article illustrates how behavioral-genetic methods are being newly applied to detect the best candidates for genuine environmental causes among the many risk factors for antisocial behavior. Second, the article examines findings of interaction between genes and environments (G x E) associated with antisocial behavior, outlining steps for testing hypotheses of measured G x E. Third, the article envisages future work on gene-environment interplay, arguing that it is an interesting and profitable way forward for psychopathology research.

Antisocial Personality Disorder↗
PubMed2000

Celiac disease and TNF promoter polymorphisms.

The possibility that genetic susceptibility to celiac disease (CD) might be influenced by tumor necrosis factor (TNF) genes polymorphism has repeatedly been put forward. To date, this has only been investigated in case-control studies and results have been contradictory. In order to avoid any possible ethnic mismatching between patients and controls, we have approached this problem studying 71 celiac families, establishing the parental haplotypes and comparing CD versus control haplotypes (the so-called AFBAC or affected family-based controls). We used DNA-based methods to screen for HLA-DRB1, -DQA1, and -DQB1 alleles, TNFalpha promoter polymorphims and TNFa and b microsatellites. The guanine-to-adenine polymorphism at position -308 of the TNFalpha gene promoter region was found associated with CD as the TNF-308A allele appeared significantly increased in frequency in CD haplotypes, and this was shown to be independent of the association between CD and the DRB1*0301,DQA1*0501,DQB1*0201 alleles. Our results indicate that at least another gene, in addition to the known association of CD with HLA class II, has a susceptibility role in this disease. This should be either TNFalpha or another polymorphic gene in the telomeric end of the HLA class III region.

Celiac Disease↗
PubMed2002

Intron presence-absence polymorphism in Drosophila driven by positive Darwinian selection.

Comparisons of intron-exon structures between homologous genes in different eukaryotic species have revealed substantial variation in the number of introns. These observations imply that, in each case, an intron presence-absence polymorphism must have existed in the past. Such a polymorphism, created by a recent intron-loss mutation, is reported here in a eukaryotic organism. This gene structure, detected in the jingwei (jgw) gene, segregates at high frequency (77%) in natural populations of Drosophila teissieri and is associated with a marked change in mRNA levels. Furthermore, the intron loss does not result from a mRNA-mediated mechanism as is usually proposed, but from a partial deletion at the DNA level that also results in the addition of four new amino acids to the JGW protein. Population genetic analyses of the pattern of nucleotide variation surrounding the intron polymorphism indicate the action of positive Darwinian selection on the intron-absent variant. Forward simulations suggest that the intensity of this selection is weak to moderate, roughly equal to the selection intensity on most replacement mutations in Drosophila.

Animals↗
PubMed2003

[Familial dilated cardiomyopathy: current status and clinical benefits of basic research].

Idiopathic dilated cardiomyopathy (DCM) is a familial disease in at least 20 to 30% of all cases. Knowledge of the genetic basis of familial DCM has been obtained only recently. Mutations in the genes responsible for sarcomere and cytoskeletal protein synthesis have been identified as the cause of DCM, and several hypotheses have been put forward to explain the etiology and pathology of the disease. However, DCM has several causes, and a number of environmental factors influence its course. This review aims to describe the current status of research on familial DCM in the areas of genetics and molecular biology, and to report the clinical applications of this new knowledge. Cooperation between clinical researchers and colleagues in molecular genetics is essential for progress in enhancing our knowledge of this disease.

Biomedical Research↗
PubMed1996

Do animal models have a place in the genetic analysis of quantitative human behavioural traits?

It seems that the genetic basis of common psychiatric diseases such as schizophrenia and manic-depressive psychosis is amenable to the genetic mapping strategies that have been successful in other complex disorders such as diabetes. The next challenge is the genetic dissection of quantitative behavioural traits such as mood, personality and intelligence. Quantitative traits pose new problems for gene cloning experiments. We argue that one way forward is by using animal models. One of the features of quantitative traits is that the DNA sequence variants which are responsible for them are unlikely to be immediately recognizable. In contrast to many qualitative traits where a discrete phenotypic difference is often the consequence of an inactivating mutation, the allelic variation responsible for quantitative traits probably has a more subtle basis. This distinction means that strategies to clone the genetic basis of quantitative behavioural traits will have to rely on functional assays of alleles thought to be important in determining the phenotype. We suggest that an efficient strategy for detecting sequences that give rise to quantitative behavioural traits can be devised in the mouse. The importance and utility of the mouse for quantitative trait analysis make it worthwhile to investigate mouse models of human behaviour; these advantages outweigh the difficulties that arise in attempts to validate the animal models. As an example we review the evidence that validates rodent emotionality as an animal model for susceptibility to human anxiety. We show that there is good evidence that rodent emotionality is a central nervous system state with a genetic basis, and that there are neuropharmacological and neuroanatomical parallels with human anxiety. Furthermore, our own work has shown that the genetic basis of the trait is relatively simple, and that the task of characterizing it at a molecular level is feasible. We expect that future experiments will show us how genetic variation gives rise to quantitative behavioural traits.

Animals↗
PubMed2004

Re-evaluating therapeutic neovascularization.

Numerous animal studies have established that neo-vascularization of ischemic tissue can be enhanced with exogenous growth factors and small clinical studies have shown encouraging results. However, the two largest randomized clinical trials to date were negative. Mechanistically, the major stimuli for neo-vascularization are hypoxia and inflammation. Hypoxia-inducible-factor (HIF-1) is a 'master switch' protein that is generated in response to hypoxia and binds to more than 40 hypoxia sensitive genes, inducing a panoply of angiogenic and protective metabolic responses. Inflammatory signals recruit T-lymphocytes and macrophages into areas of neo-vascularization which act as a source of angiogenic and arteriogenic factors. Although hypoxia and inflammation are interdependent in eliciting neo-vascular responses, angiogenesis appears to be hypoxia-dependent, whereas inflammation and hemodynamic factors drive arteriogenesis. The negative outcome of the two largest trials may have many reasons. There are issues relating to patient selection, choice of growth factor therapy, dosing and route administration, concomitant medication, trial design including the efficacy parameters that were selected and a lack of sufficient insight into the mechanisms that are responsible for neo-vascularization. In order to move forward the therapeutic objective should be switched to arteriogenesis although this process is even more poorly understood than angiogenesis. Genetic studies in mice with intrinsically different arteriogenic responses combined with studies in human populations with differences in the extent of collateral development may provide fundamental insight into arteriogenic mechanisms. Attention should also be focused on the way in which arteriogenesis is stimulated and the endpoints of clinical trials should be redefined.

Humans↗
PubMedDate not supplied

A genetic algorithm based on prepotency evolution using chaotic initiation used for network training.

The concept of "prepotency" is introduced in evolution algorithm. The logistic mapping as a simple and powerful device in the chaos theory is combined with the newly proposed prepotency evolution (PE) algorithm to formulate a new genetic algorithm. PE with a population initialized by chaotic numbers is applied to the multiple-layer feed-forward ANN training (PECNN). The logistic mapping ensures the PE starts each time from different initial population never used before. The newly designed PE operator partially includes the crossover and mutation operations implicitly. The proposed algorithm has a higher convergence speed comparing to the conventional GA. During the PE operation the distances between members would become smaller and smaller until all members turning to be almost identical with the potential best minimum being found. It does not waste searching time surrounding the testing minima like the conventional GA and not show symptoms of overfitting to the training set samples. The combination of logistic mapping and PE used in ANN training makes PECNN be able to test lots of minima rapidly and effectively. This greatly enlarges the opportunity to find the global minimum. The proposed algorithm has been testified by prediction of the frequency data of tetrahedral vibration modes (nu(1) and nu(2)) of tetrahalide MX(4)(n) ions. The results obtained by the proposed PECNN compared favorably with those of the conventional chemometric method PLS regression.

Journal Article↗