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991.
992.
Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource 总被引:9,自引:0,他引:9
Patrick M. Nolan Jo Peters Lucie Vizor Mark Strivens Rebecca Washbourne Tertius Hough Christine Wells Peter Glenister Claire Thornton Jo Martin Elizabeth Fisher Derek Rogers Jim Hagan Charlie Reavill Ian Gray John Wood Nigel Spurr Mick Browne Sohaila Rastan Jackie Hunter Steve D.M. Brown 《Mammalian genome》2000,11(7):500-506
Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis
program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for
visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol—SHIRPA.
Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic
startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical
biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating
deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail
tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse
and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the
mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map
of the mouse and assisting with the identification of genes underlying novel mutations—with consequent benefits for the analysis
of gene function and the identification of novel pathways.
Received: 16 December 1999 / Accepted: 16 December 1999 相似文献
993.
Novakova L Ruzicka E Jech R Serranova T Dusek P Urgosik D 《Neuro endocrinology letters》2007,28(1):21-25
Deep brain stimulation of the subthalamic nucleus (DBS STN) is an effective treatment method in advanced Parkinson's disease (PD) providing marked improvement of its major motor symptoms. In addition, non-motor effects have been reported including weight gain in PD patients after DBS STN. Using retrospective survey, we aimed to evaluate weight changes in our patients with advanced PD treated with DBS STN. We inquired 25 PD patients (16 men, 9 women), of mean age 55 (42-65) years, mean PD duration 15 (9-21) years, who previously received bilateral DBS STN. We obtained valid data from 23 patients. In the first survey, 1 to 45 months after DBS, weight gain was found in all patients comparing to pre-DBS period. The mean increase was 9.4 kg (from 1 to 25 kg). The patients' mean body mass index (BMI) increased from 23.7 to 27.0 kg/m2, i.e. by 3.3 kg/m2 (+2 to +6.1 kg/m2). In the repeated survey one year later, in 12 of the patients body weight moderately decreased, 3 did not change, and 6 patients further increased their weight. Possible explanations of body weight gain after DBS STN include a reduction of energy output related to elimination of dyskinesias, improved alimentation or direct influence on function of lateral hypothalamus by DBS STN. 相似文献
994.
Klonowska A Chaintreuil C Tisseyre P Miché L Melkonian R Ducousso M Laguerre G Brunel B Moulin L 《FEMS microbiology ecology》2012,81(3):618-635
Rhizobia are soil bacteria able to develop a nitrogen-fixing symbiosis with legumes. They are taxonomically spread among the alpha and beta subclasses of the Proteobacteria. Mimosa pudica, a tropical invasive weed, has been found to have an affinity for beta-rhizobia, including species within the Burkholderia and Cupriavidus genera. In this study, we describe the diversity of M.?pudica symbionts in the island of New Caledonia, which is characterized by soils with high heavy metal content, especially of Ni. By using a plant-trapping approach on four soils, we isolated 96 strains, the great majority of which belonged to the species Cupriavidus taiwanensis (16S rRNA and recA gene phylogenies). A few Rhizobium strains in the newly described species Rhizobium mesoamericanum were also isolated. The housekeeping and nod gene phylogenies supported the hypothesis of the arrival of the C.?taiwanensis and R.?mesoamericanum strains together with their host at the time of the introduction of M.?pudica in New Caledonia (NC) for its use as a fodder. The C.?taiwanensis strains exhibited various tolerances to Ni, Zn and Cr, suggesting their adaptation to the specific environments in NC. Specific metal tolerance marker genes were found in the genomes of these symbionts, and their origin was investigated by phylogenetic analyses. 相似文献
995.
Raybaud A Dodier Y Bissonnette P Simoes M Bichet DG Sauvé R Parent L 《The Journal of biological chemistry》2006,281(51):39424-39436
The putative hinge point revealed by the crystal structure of the MthK potassium channel is a glycine residue that is conserved in many ion channels. In high voltage-activated (HVA) Ca(V) channels, the mid-S6 glycine residue is only present in IS6 and IIS6, corresponding to G422 and G770 in Ca(V)1.2. Two additional glycine residues are found in the distal portion of IS6 (Gly(432) and Gly(436) in Ca(V)1.2) to form a triglycine motif unique to HVA Ca(V) channels. Lethal arrhythmias are associated with mutations of glycine residues in the human L-type Ca(2+) channel. Hence, we undertook a mutational analysis to investigate the role of S6 glycine residues in channel gating. In Ca(V)1.2, alpha-helix-breaking proline mutants (G422P and G432P) as well as the double G422A/G432A channel did not produce functional channels. The macroscopic inactivation kinetics were significantly decreased with Ca(V)1.2 wild type > G770A > G422A congruent with G436A > G432A (from the fastest to the slowest). Mutations at position Gly(432) produced mostly nonfunctional mutants. Macroscopic inactivation kinetics were markedly reduced by mutations of Gly(436) to Ala, Pro, Tyr, Glu, Arg, His, Lys, or Asp residues with stronger effects obtained with charged and polar residues. Mutations within the distal GX(3)G residues blunted Ca(2+)-dependent inactivation kinetics and prevented the increased voltage-dependent inactivation kinetics brought by positively charged residues in the I-II linker. In Ca(V)2.3, mutation of the distal glycine Gly(352) impacted significantly on the inactivation gating. Altogether, these data highlight the role of the GX(3)G motif in the voltage-dependent activation and inactivation gating of HVA Ca(V) channels with the distal glycine residue being mostly involved in the inactivation gating. 相似文献
996.
997.
Lucie Crépin Thibault Nidelet Isabelle Sanchez Sylvie Dequin Carole Camarasa 《Applied and environmental microbiology》2012,78(22):8102-8111
The efficiency of nitrogen use is a key determinant of the completion of alcoholic fermentation. We analyzed the kinetics of consumption of 18 nitrogen compounds by 14 Saccharomyces cerevisiae strains of various origins in a synthetic medium that mimicked a grape must. The kinetic profiles of total nitrogen consumption were diverse, but the order of nitrogen source consumption was similar for all strains. The nitrogen compounds could be classified into three groups, according to their order of use: prematurely consumed (Lys), early consumed (Asp, Thr, Glu, Leu, His, Met, Ile, Ser, Gln, and Phe), and late consumed (ammonium, Val, Arg, Ala, Trp, and Tyr). The initial concentrations of these compounds did not alter the order in which they were consumed, except for arginine and ammonium. Early consumed amino acids are transported by specific permeases under Ssy1p-Ptr3p-Ssy5 (SPS)-mediated control that are expressed at the beginning of consumption. Most nitrogen compounds consumed late are transported by permeases under nitrogen catabolite repression (NCR), and others (Val, Trp, and Tyr) are transported by SPS-regulated low-affinity permeases. Therefore, the kinetic characteristics of transporters, as well as SPS and NCR, are likely key factors controlling the temporal sequence of consumption of nitrogen compounds and constitute a system highly conserved in S. cerevisiae species. This work sheds new light on the mechanistic basis of the sequential use of different nitrogen compounds in complex environments. 相似文献
998.
A single-cell isolate of Amphidinium from the northern Caribbean Sea was identified as A. operculatum Clap. et Lack. var. nov. gibbosum Maranda et Shimizu based on a morphological and ultrastructural study. This free-swimming dinoflagellate, which was found to produce potent antitumor metabolites, is elongate and asymmetrical. It is compared with two close relatives A. klebsii Kofoid et Swezy and A. carterae Hulburt. Amphidinium operculatum var. gibbosum can be distinguished from A. klebsii on the basis of shape while it differs from A. carterae on the basis of size, shape, cell surface, and chloroplast arrangement. The shape and size of the nucleus and the presence of mucocysts also differentiate the gibbosum variety from its two relatives. The architecture of the pusule may ultimately provide the best ultrastructural discriminating character. Otherwise, the general ultra-structure of the Caribbean isolate is typical of many unarmored photo synthetic dinoflagellates with amphiesma, condensed chromosomes, trichocysts, mitochondria with tubular cristae, and trilamellar chloroplasts. 相似文献
999.
Thin films of binary C60/Ti composites, with various concentrations of Ti ranging from ~ 25% to ~ 70%, were deposited on microscopic glass coverslips and were tested for their potential use in bone tissue engineering as substrates for the adhesion and growth of bone cells. The novelty of this approach lies in the combination of Ti atoms (i.e., widely used biocompatible material for the construction of stomatological and orthopedic implants) with atoms of fullerene C60, which can act as very efficient radical scavengers. However, fullerenes and their derivatives are able to generate harmful reactive oxygen species and to have cytotoxic effects. In order to stabilize C60 molecules and to prevent their possible cytotoxic effects, deposition in the compact form of Ti/C60 composites (with various Ti concentrations) was chosen. The reactivity of C60/Ti composites may change in time due to the physicochemical changes of molecules in an air atmosphere. In this study, we therefore tested the dependence between the age of C60/Ti films (from one week to one year) and the adhesion, morphology, proliferation, viability, metabolic activity and potential DNA damage to human osteosarcoma cells (lines MG-63 and U-2 OS). After 7 days of cultivation, we did not observe any negative influence of fresh or aged C60/Ti layers on cell behavior, including the DNA damage response. The presence of Ti atoms resulted in improved properties of the C60 layers, which became more suitable for cell cultivation. 相似文献
1000.
Three new polyamine conjugates with stigmasterol [(3β,22E)-stigmasta-5,22-dien-3-ol] were synthesized and subjected to basic antimicrobial and cytotoxic tests. The conjugate derived from spermine, (3β,22E)-stigmasta-5,22-dien-3-yl 4(12-amino-4,9-diaza-dodecylamino)-4-oxobutanoate (5c), displayed considerable antimicrobial activity on Staphylococcus aureus at low concentration (50μgmL(-1)). The cytotoxic activity was tested on cells of human T-lymfoblastic leukemia (IC(50)=35.8±10.3μM (5c) and IC(50)=35.9±5.7μM (5b)) and normal human fibroblasts (IC(50)=38.0±2.8μM (5c) and IC(50)=45.5±1.9μM (5b)). Conjugate 5a displayed no activity in both tests. 相似文献