The industrial exploitation of genomes DNA sequence--new EC genomes special edition.
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DNA↗
Biomedical subjects
S M Thomas
Publications and source records attributed to S M Thomas.
Visual and audiovisual speech perception with color and gray-scale facial images.
Research has shown that auditory speech recognition is influenced by the appearance of a talker's face, but the actual nature of this visual information has yet to be established. Here, we report three experiments that investigated visual and audiovisual speech recognition using color, gray-scale, and point-light talking faces (which allowed comparison with the influence of isolated kinematic information). Auditory and visual forms of the syllables /ba/, /bi/, /ga/, /gi/, /va/, and /vi/ were used to produce auditory, visual, congruent, and incongruent audiovisual speech stimuli. Visual speech identification and visual influences on identifying the auditory components of congruent and incongruent audiovisual speech were identical for color and gray-scale faces and were much greater than for point-light faces. These results indicate that luminance, rather than color, underlies visual and audiovisual speech perception and that this information is more than the kinematic information provided by point-light faces. Implications for processing visual and audiovisual speech are discussed.
Adolescent↗
Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses.
The alpha4 integrins are indispensable for embryogenesis, haematopoiesis and immune responses, possibly because alpha4 regulates cellular functions differently from other integrins through its cytoplasmic tail. We used novel mimics of the alpha4 tail to identify molecules that could account for alpha4-specific signalling. Here we report that the alpha4 tail, but not several other alpha-subunit tails, binds tightly to the signalling adaptor paxillin. Paxillin physically associated with alpha4 integrins in Jurkat T cells at high stoichiometry, and joining the alpha4 tail to alphaIIb resulted in a complex of integrin alphaIIbbeta3 with paxillin. This association markedly enhanced the rates of alphaIIbbeta3-dependent phosphorylation of focal adhesion kinase and cell migration. It also reduced cell spreading, focal adhesion and stress fibre formation. A point mutation within the alpha4 tail that disrupts paxillin binding reversed all of these effects. Furthermore, alpha4beta1-dependent adhesion to VCAM-1 led to spreading of mouse embryonic fibroblasts derived from paxillin-null but not from wild-type mice. Thus, the tight association of paxillin with the alpha4 tail leads to distinct biochemical and biological responses to integrin-mediated cell adhesion.
Animals↗
The application of a linear algebra to the analysis of mutation rates.
Cells and bacteria growing in culture are subject to mutation, and as this mutation is the ultimate substrate for selection and evolution, the factors controlling the mutation rate are of some interest. The mutational event is not observed directly, but is inferred from the phenotype of the original mutant or of its descendants; the rate of mutation is inferred from the number of such mutant phenotypes. Such inference presumes a knowledge of the probability distribution for the size of a clone arising from a single mutation. We develop a mathematical formulation that assists in the design and analysis of experiments which investigate mutation rates and mutant clone size distribution, and we use it to analyse data for which the classical Luria-Delbrück clone-size distribution must be rejected.
Animals↗
Plant DNA patents in the hands of a few.
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Agriculture↗
The illusory-letters phenomenon: an illustration of graphemic restoration in visual word recognition.
We present a demonstration of word perception in which stimuli containing very few letters (just 50% of their original number) are presented for unlimited durations and yet are seen unequivocally as complete words. The phenomenon suggests that recognition of words can be achieved even when perception of their component letters is prevented.
Humans↗
Evaluation of transcriptional fusions with green fluorescent protein versus luciferase as reporters in bacterial mutagenicity tests.
A bacterial plasmid was constructed on which the regulatory region of the umuC gene of Escherichia coli was fused to the coding sequence of the green fluorescent protein gene (gfp) from the jellyfish Aequorea victoria. Escherichia coli AB1157 strains carrying the plasmid emitted fluorescence in the presence of mutagens that induce the SOS DNA repair system. Data on tests with nitrosoguanidine, methylmethane sulphonate and UV radiation (254 nm) are presented. Although fluorescent detection using this system was not as rapid or sensitive as a similar luminescent equivalent (umuC-luxAB), the gfp reporter system was more robust. Escherichia coli umu gene induction was also analysed in Salmonella typhimurium TA1537 cells following plasmid transfer and exposure to the same range of mutagens. There was no significant difference in sensitivity between the two species. These preliminary results will provide the basis for development of mutagenicity test systems useful in the testing of complex mixtures, such as environmental samples, and the investigation of physiological parameters influencing spontaneous mutagenesis in bacteria.
Animals↗
Chronic parvovirus B19 meningitis in a child with acute lymphocytic leukemia.
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Child, Preschool↗
Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2.
The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2 binds to SHP substrate 1 (SHPS-1)/SIRP-1alpha, a transmembrane glycoprotein with adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887-6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223-13229). Therefore, we asked whether SHP2-SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl phosphorylation increased upon plating of murine fibroblasts onto specific extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1 tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced mitogen-activated protein kinase (MAPK) activation, and potentiation required functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we analyzed the responses of SHP-2 exon 3(-/-) and wild-type cell lines to being plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl phosphorylation of several focal adhesion proteins, MAPK activation, and the ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but were restored upon SHP-2 expression. Our data suggest a positive-feedback model in which, upon integrin engagement, basal levels of c-Src activity catalyze the tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces positive signals for downstream events such as MAPK activation and cell shape changes.
Animals↗
Preponderance of hypokalaemia as a cause of acute onset quadriparesis in northern India/southern Nepal.
Of 68 patients who were admitted with acute quadriparesis to a hospital in northern India, over 70% were found to be hypokalaemic. The most common cause of hypokalaemia was that associated with gastroenteritis (54%). These patients had all received intravenous fluids previously. It is likely that their hypokalaemia was caused by gastrointestinal loss compounded by parenteral fluid replacement. The next most common group of hypokalaemia-associated quadriparesis had no obvious cause for hypokalaemia (38%). Hypokalaemia-induced quadriparesis is a potentially life-threatening illness which can be readily treated with potassium supplements. The physician should consider hypokalaemia in patients who present with acute onset quadriparesis, and even if diagnostic tests for hypokalaemia are not available, should consider a judicious trial of potassium supplementation empirically, provided that there are no contraindications.
Acute Disease↗
Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin.
Paxillin is a focal adhesion scaffolding protein which was originally identified as a substrate of the oncogenic tyrosine kinase, v-src. Paxillin has been proposed to be involved in regulation of focal adhesion dynamics. Two alternatively spliced mouse paxillin cDNAs were cloned and in the process, a paxillin-related protein, Hic-5, was also identified. Cloning and characterization of Hic-5 indicates that this protein shares extensive homology with paxillin. Although Hic-5 was originally characterized as a TGF-beta-inducible gene and proposed to be a transcription factor involved in senescence, the studies here demonstrate that Hic-5 is localized to focal adhesion in REF52 cells and can interact with the focal adhesion proteins, Fak, Frnk, and vinculin. In addition, like paxillin, Hic-5 can bind to a negative regulator of Src PTKs, csk but does not bind to the adaptor protein Crk. Like paxillin, localization of this protein to focal adhesions is mediated primarily by the LIM domains; however, sequences outside the LIM domains also play a minor role in focal adhesion targeting. These results suggest that Hic-5 like paxillin could be involved in regulation of focal adhesion dynamics and raise the possibility that Hic-5 and paxillin could have overlapping or opposing functions in the overall regulation of cell growth and differentiation.
Amino Acid Sequence↗
Genomics: the implications for ethics and education.
Over the past 10 years, the identification of disease genes has been expanding rapidly. Those identified in the earlier part of the decade were largely achieved through positional cloning and the majority are for relatively rare disorders which involve single genes. As the Human Genome Mapping Project has progressed, the rate of gene discovery has increased substantially through the development of new DNA sequencing techniques and in silico approaches. The human genome will have been largely sequenced by ther Spring 2000. We can expect the identification of large numbers of susceptibility genes for common multifactorial polygenic diseases as well as genes which are associated with human behavioural traits. Some of these advances hold out the prospects of real progress in the diagnosis and treatment of a wide range of disorders. However, for many individuals, increased knowledge about their genes will present ethical dilemmas which are difficult to resolve. There are also wider ethical issues which concern the use of genetic information by insurers and employers and yet others which concern ownership and access. In this chapter, the main ethical issues raised by the impact of genomics on healthcare are discussed. The role of education in enabling individuals and health professionals to meet these challenges is also considered.
Ethics, Medical↗
Perceptions of cancer and its causes among "Industrial Corridor" residents: the LMRICS Planning Project. Lower Mississippi River Interagency Cancer Study.
The Industrial Corridor is composed of 11 parishes heavily concentrated with petrochemical facilities along the Mississippi River from Baton Rouge to the mouth of the river. There exists a generalized belief that the proximity of these waste-emitting industries to residential areas has adversely impacted the health of the residents including increasing the rates of cancer. At the same time, Louisiana Tumor Registry data do not support the widely held belief of excess cancer rates in the corridor. A community in the corridor was chosen to explore the issues of health beliefs, health-seeking behavior, and perceived quality of life. An extensive questionnaire was developed and administered to a sample of community residents. The results of the questionnaire suggest there may be multiple factors that influence the perceived well-being and preventive health practices of corridor residents.
Black or African American↗
Continuous culture dynamics for aniline metabolism by Pseudomonas sp. CIT1.
Inhibition by toxic substrates enables multiple steady states to arise in biodegradation systems. This phenomenon was investigated for the continuous metabolism of aniline by Pseudomonas sp. CIT1. Differences of various metabolic parameters between the two growth regimes (uninhibited and inhibited) and the transient response to a step-up in dilution rate were determined. Regulatory mechanisms consistent with the experimental evidence are proposed. Aniline is the transcriptional inducer of a metabolic pathway that converts aniline to TCA cycle intermediates. The suite of enzymes is coordinately expressed from a single promoter. We followed the level of the pathway mRNA using a fragment containing the catechol 2,3 dioxygenase gene (andioxB) and monitored the pathway enzyme activity using catechol 2,3 dioxygenase (C23D). The inhibited regime resulted in a 60% lower growth yield, near constant levels of C23D monomer, but a 50% reduction in the specific activity of C23D, increased RNA synthesis rates (total and aniline pathway mRNA), and elevated RNA decay rates. Elucidation of regulatory mechanisms indicates that C23D is noncompetitively inhibited by aniline and subject to feedback inhibition by 2-hydroxymuconic semialdehyde (HMS). During uninhibited growth regime operation, metabolism of HMS is the rate-limiting step; in contrast, conversion of aniline to catechol limits growth in the inhibited regime.
Aniline Compounds↗
Construction of a umuC'-luxAB plasmid for the detection of mutagenic DNA repair via luminescence.
This paper describes a novel system for the detection of mutagenic DNA repair in Escherichia coli. The DNA damage inducible umuC gene of Escherichia coli has been fused to the luxAB genes from Vibrio harvleyi that encode the enzyme luciferase. Mutagenicity has been assessed semi-quantitatively by the induction of bioluminescence. This system is simple, rapid and equivalent in sensitivity to other currently available test procedures. Its use in the detection of known SOS mutagens MMS, MNNG and UV is described.
Artificial Gene Fusion↗
The commercial development of gene therapy in Europe and the USA.
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Biotechnology↗
Trends in the use of pelvimetry techniques.
Assessment of maternal pelvic dimensions is usually considered necessary where vaginal delivery is contemplated in a breech presentation or if reduced pelvic dimensions are suspected in a current or previous pregnancy. Pelvimetry techniques include computed tomography (CT), conventional radiography, digital fluorography and magnetic resonance imaging (MRI). The first three techniques result in a radiation dose to mother and fetus which, depending on how the technique is performed, can vary by up to 40-fold. Of the techniques using X-rays, CT pelvimetry with a lateral scanogram generally gives the lowest radiation dose and conventional radiography using an air gap technique with a single lateral view is a relatively low-dose alternative where CT is not available. A questionnaire was sent to 227 hospitals during 1993 and 1996 to assess whether there was a move towards lower dose techniques of pelvimetry. The results show a trend away from conventional pelvimetry (48.4% in 1993 to 28% in 1996) with a small proportion of centres using MRI (4%) in 1996. Of the centres still using conventional pelvimetry, relatively few were using a low-dose air-gap technique (2.1% in 1993 to 10.9% in 1996). An increasing majority of centres were using one-view CT (69.3% in 1993 and 80.4% in 1996) but a significant proportion were still performing more than one view. This study shows that there was a move towards lower dose techniques of pelvimetry but that there were still many hospitals that had not implemented a policy of reducing radiation exposure in these patients.
Female↗
Update on endovascular management of arterial occlusive disease.
Although balloon angioplasty is the most widely used technique for treating peripheral vascular disease, developments in endovascular therapies have extended methods of percutaneous vascular intervention. Lasers have been used to recanalize occluded arteries. Mechanical devices can remove obstructions and metallic stents can be placed to keep a vessel open with good long-term patency.
Angiography, Digital Subtraction↗