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  • Articles  (2,478)
  • Mice  (2,478)
  • 2000-2004  (1,035)
  • 1995-1999  (836)
  • 1980-1984  (485)
  • 1975-1979  (122)
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  • Articles  (2,478)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Neuroscience and behavioral physiology 30 (2000), S. 195-200 
    ISSN: 1573-899X
    Keywords: Mice ; dominance ; subordinacy ; stress ; aggression ; locomotor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The behavior of individaals and their responses to external stimuli are controlled by the microsocial environment, which for most mammals is associated with dominant-subordinate relationships. Physiological and behavioral differences between dominant and subordinate individuals may be ‘primary’ (genetically determined) or ‘secondary’ (due to position in the group's hierarchical structure). A series of experiments was conducted to investigate the physiological (pain response threshold), immunological (thymus, spleen weights, primary immune response), and behavioral (motor activity, behavior in a shuttle box test) characteristics of dominant and subordinate individuals in groups of three laboratory mice formed on the basis of linear hierarchy. Assessment of the effects of group conditions was made using a conditioned reflex location preference test. The results showed: 1) there are no statistically significant differences in physiological and behavioral (except for motor activity) parameters between dominant and subordinate mice; 2) co-housing of dominant and subordinate individuals in groups with stable hierarchical relationships was not aversive for them.
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  • 2
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    Journal of biomedical science 2 (1995), S. 146-153 
    ISSN: 1423-0127
    Keywords: Transgene ; Mice ; Embryogenesis ; HIV ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The likelihood that expression of a foreign gene in a mammalian cell is deleterious to viability is confronted whenever novel transgenic animals are made. A pathological response to transgene expression is even desired in transgenic mouse models of human disease. The derivation of HIV-transgenic mice in our laboratory using multiple recombinant forms of an HIV provirus has resulted in mixed success best explained by the variable toxicity of the different transgenes. Employing a standardized approach to pronuclear injections, experimental variation amongst recombinant HIV transgenes was documented in terms of the percentage of pregnancies following embryo transfer into pseudopregnant mice and the percentage of transplanted embryos leading to term births in these pregnant females (giving rise to an index of birth success, SI). Results compiled over 5 years suggested that the SI reflected transgene toxicity, in this case of HIV gene products early in embryogenesis. These observations have guided the design of productive transgenes for mouse models of HIV-related diseases and may be generally applicable in transgenesis.
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  • 3
    ISSN: 1423-0127
    Keywords: Enterovirus type 71 ; Experimental infection ; Mice ; Neutralizing antibody ; Vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Experimental infection with enterovirus type 71 (EV71) induced death in neonatal mice in an age- and dose-dependent manner. The mortality rate was 100% following intraperitoneal inoculation 1-day-old ICR mice and this gradually decreased as the age at the time of inoculation increased (60% in 3-day-old mice and no deaths occurred in mice older than 6 days of age). A lethal dose greater than 108 PFU was necessary. Lethargy, failure to gain weight, rear limb tremors and paralysis were observed in the infected mice before death. EV71 was isolated from various tissues of the dead mice. Using a reverse transcription polymerase chain reaction technique with a specific primer pair, a 332-bp product was detected in the tissues that produced a culture positive for EV71. Protection against EV71 challenge in neonatal mice was demonstrated following passive transfer of serum from actively immunized adult mice 1 day after inoculation with the virus. Pups from hyperimmune dams were resistant to EV71 challenge. Additionally, maternal immunization with a formalin-inactivated whole-virus vaccine prolonged the survival of pups after EV71 lethal challenge.
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  • 4
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    Calcified tissue international 27 (1979), S. 19-26 
    ISSN: 1432-0827
    Keywords: Bone diseases ; Familial hypophosphatemia ; Magnesium ; Mice ; Phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A new genetic mutant in mice,Hyp, has been proposed as a model for the human disease X-linked hypophosphatemia (the most common form of vitamin D-resistant rickets). The gene is X-linked, dominant, and produces reduced renal tubular reabsorption of phosphate, hypophosphatemia, and dwarfism. Our goal was to evaluate the skeletal changes histologically and to measure chemically the prominant blood and bone minerals to judge the suitability of this mutant as a model for the human disease. Thirteen-week-old hemizygousHyp male mice were compared with their normal littermate controls. TheHyp mice were hypocalcemic, hypophosphatemic, hypermagnesemic, and had elevated plasma alkaline phosphatase. The femur ash weighed less than half the normal ash weight but had a normal Ca:P ratio. The ash composition was high in %Na and K but low in %Mg. The mandibular incisor ash was also low in %Mg. Histologically the femur showed wide osteoid borders and wide epiphyseal plate. Microradiography revealed reduced bone density and enlarged osteocyte lacunae. Skeletal muscle samples, although smaller in theHyp mice, showed no striking alternations in inorganic or total phosphate content, dry weight (as % wet weight), or extracellular fluid space. TheHyp gene in mice seems to produce a condition similar to that of X-linked hypophosphatemia in humans.
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  • 5
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    Calcified tissue international 28 (1979), S. 259-262 
    ISSN: 1432-0827
    Keywords: C-type virus particles ; Bone tissue ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The proximal tibial metaphysis of apparently healthy strain 101 mice, 3–4 weeks old, and (C3H×101)F1 hybrids, 3–48 weeks old, was studied by electron microscopy. Budding, immature, and mature C-type virus particles were found within trabecular bone tissue of 3 of 8 strain 101 and 4 of 12 (C3H×101)F1 mice. The particles were most common in lacunae of aging osteocytes and were only occasionally associated with osteoblasts. Although the morphology of budding and immature particles appeared to be identical with that of typical C-type viruses, most of the mature forms of particles showed atypical structure and size. The electron-dense core was very large and not clearly defined, measuring approximately 70–130 nm in diameter. This diffuse core sometimes completely filled the space within the envelope of the particles. The diameters of the pleomorphic mature C-type particles ranged from approximately 90 to 150 nm. The possible association between the production of pleomorphic C-type virus particles by bone cells and spontaneous osteomagenesis in 101 and (C3H × 101)F1 mice is discussed.
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  • 6
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    Calcified tissue international 36 (1984), S. 662-667 
    ISSN: 1432-0827
    Keywords: Vitamin D ; Hyp ; X-linked hypophosphatemia ; Metabolic bone disease ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Hyp mice are a model for human X-linked hypophosphatemia (vitamin D-resistant rickets.) To determine whether an abnormality of vitamin D metabolism exists in this disease, the profiles of the metabolites of vitamin D were determined in normal andHyp mouse plasma.Hyp and normal mice were fed a vitamin D-deficient diet and received 1,23H-vitamin D3 at 16 Ci/mmol by stomach tube at 5 ng/g body weight (0.21 µCi/g b.w.) on alternate days for 14 days. The dose of vitamin D given maintained near normal plasma 25-OH-vitamin D. Thus the mice were in a vitamin D-replete state with all metabolite pools labeled with3H. Plasma was collected from 4 normal and 4Hyp mice. The plasma was extracted, and the extracts were chromatographed separately for each mouse on an LH-20 column. Each major peak of radioactivity was rechromatographed using high performance liquid chromatography on a Zorbax-Sil column using solvent systems known to resolve several vitamin D metabolites. Twenty-one radioactive peaks were identified. The disintegrations per minute of3H in each peak were quantified and converted to plasma concentration using the known specific activity of the administered vitamin D. The 25-OH-vitamin D accounted for 55% of the circulating radioactivity, and 24,25-(OH)2-vitamin D accounted for 22%. The plasma levels of 24,25-(OH)2-vitamin D were similar to levels previously reported by us using protein binding assays. No peaks of radioactivity were missing in the plasma extracts of theHyp mice. Also there was no evidence that plasma 24,25-(OH)2-vitamin D was elevated in theHyp mice.
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  • 7
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    Theoretical and applied genetics 62 (1982), S. 281-287 
    ISSN: 1432-2242
    Keywords: Growth ; Alkaline phosphatase ; Selection ; Correlated responses ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The effectiveness of two way selection for plasma alkaline phosphatase (ALP) was investigated in order to determine its influences on growth traits through thirteen generations. The responses of the two lines selected for high (HP) and low (LP) ALP at 45 days of age were compared to that of the mice selected for large (L) and small (SM) body size. The selection responses of plasma ALP were very effective for both HP and LP lines, with average responses per generation calculated from linear regressions of 0.227±0.037 and −0.088±0.022 respectively. The final levels of ALP in HP and LP were 5.54±0.71 and 1.27±0.20 in the thirtheenth generation, while the SM, L and base population had levels of 3.49±0.08, 0.86±0.55 and 2.77±0.56 respectively. The body weight at 45 days of age in LP (31.4±1.4 g) as a correlated response was significantly higher than HP (23.4±1.8 g) at generation 10. The correlated response of milk yield, measured by weight gain up to 12 days of age, was significantly greater in the LP line than in HP, but the correlated response of gains after weaning was not so different as the response of milk yield. The response of litter size and weight in LP showed significant higher levels than that of HP, but pups' birth weight did not differ between LP and HP. It is suggested that the correlated response of milk yield contributed more to the divergence of body size between HP and LP than the gain after weaning. Realized heritabilities of ALP were 0.335±0.059 (HP) and 0.279±0.051 (LP). Realized genetic correlations between ALP and 45 days' body weight were −0.27±0.13 (HP with SM) and −0.52±0.19 (LP with L). Realized genetic correlations between ALP and milk yield were −0.95±0.03 (HP) and −0.37±0.29 (LP). Correlations between ALP and postweaning gains were fairly low.
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  • 8
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    Theoretical and applied genetics 63 (1982), S. 145-150 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Growth rate ; ad libitum feeding ; Restricted feeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Selection for post-weaning weight gain in mice from 21 to 42 days, on either a full or restricted feeding level during this period was carried out for seven generations. Control lines were maintained for each feeding level. The rate of selection response was higher on full feeding due to a higher heritability and a larger phenotypic variance. Realised heritabilities of 0.29±0.05 and 0.19±0.04 for selection on full and restricted feeding respectively, were in close agreement with base population estimates. Selection on full feeding led to positive correlated responses in 21 day weight, 42 day weight, food intake and efficiency between 21 and 42 days, and 42 day tail length, but with little change in reproductive performance. Correlated responses to selection on restricted feeding were reduced 21 day weight, but an increase in 42 day weight and increased efficiency from 21 to 42 days. However, overall reproductive performance fell.
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  • 9
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    Theoretical and applied genetics 67 (1984), S. 479-484 
    ISSN: 1432-2242
    Keywords: Heterosis ; Lifetime performance ; Mice ; Male and female ; Mate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Six straightbred lines of mice, some of their F1 crosses and a synthetic line were used to evaluate male and female contributions to heterosis in lifetime performance measured on females. Females from each straightbred line or F1 crosses were pair-mated randomly at day 42 with either a male of the corresponding genetic group or from a synthetic line, and pairs were maintained for 155 days (lifetime). Each mother was allowed to rear all young born alive until day 18 when the young were discarded. Data were analyzed using a model in which the group mean of lifetime performance was expressed as the sum of (additive direct) genetic and environmental effects for each of the male and female genetic groups used for mating. Comparison of group means for lifetime performance revealed that estimates of F1 heterosis due to male and female averaged 10 and 9% for number of parturitions during lifetime, 7 and 28% for total number of young born alive, 6 and 31% for total body weight of young born alive, 8 and 33% for total number of young raised to day 18, 9 and 43% for total body weight of young raised to weaning, and 8 and 8% for days from first mating to last parturition. The male's contribution to heterosis in lifetime performance was smaller than female's contribution for productive traits (total number of young born alive and at day 18, and total body weight of young born alive and at day 18), and was nearly equal in reproductive traits (number of parturitions during lifetime and days from first mating to last parturition).
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  • 10
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    Theoretical and applied genetics 91 (1995), S. 340-345 
    ISSN: 1432-2242
    Keywords: Selection index ; Restricted index ; Fat ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The objective of this study was to determine if low secondary selection differentials, caused by selecting within full-sib families, may have accounted for the failure of an intended restricted selection index to reduce epididymal fat pad weight (EF) without changing body weight (BW) in mice. Replicate lines that had been selected within full-sib families for high (HE) or low (LE) EF, while holding BW constant, were crossed. After two generations of random mating, two replicates were sampled and selection initiated for the same restricted index criteria except that mass selection was used to increase the selection differentials. In both phases of selection the HE restricted index selection, designed to increase EF without altering BW, was in agreement with expectation. In contrast, the LE index, designed to decrease EF without changing BW, did not agree with theory since BW increased while EF decreased only slightly. Therefore, reduced selection differentials could not explain the deviation from theory. A possible explanation may reside in the restricted selection index being more sensitive to changes in genetic parameters due to shifts in gene frequency as a consequence of the selection applied. However, linkage disequilibrium and genetic drift can not be ruled out as contributing factors to the asymmetry of response.
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  • 11
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    Theoretical and applied genetics 64 (1983), S. 275-281 
    ISSN: 1432-2242
    Keywords: Fused gene ; Mice ; Hydrocortisone ; Gene inactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary This study was undertaken to examine the effects of hydrocortisone injected into male mice on the phenotypic expression and inheritance of the Fused (Fu) gene in their offspring. Data were obtained indicating that there is a hydrocortisone-susceptible period during spermatogenesis. Hydrocortisone injections of males during this period resulted in a statistically significant decrease in the proportion of phenotypically Fu offspring. Genetic analysis with the use of the closely linked recessive marker tufted (tf) demonstrated that the deficit of phenotypically Fu individuals among offspring is not caused by the differential death of gametes, zygotes or embryos. According to genetic data, this deficit is due to a decrease in the penetrance of the Fu gene and partly to its inherited inactivation. The possible mechanisms of the observed phenomenon are discussed.
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  • 12
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    Theoretical and applied genetics 67 (1984), S. 113-122 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Growth ; Genetic correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Four lines of mice were formed from a common base population and selected for 37 generations for either increased 3-week weight (weaning weight), 6-week weight, 3–6 week gain, or maintained as a randomly bred control line. Realised heritability estimates for short-term (long-term) responses were 0.33±0.20 (0.07±0.10), 0.46±0.14 (0.26±0.09), 0.36±0.14 (0.24±0.11) for 3-week weight, 6-week weight and 3–6 week gain, respectively. Realised genetic correlations estimated from short-term (long-term) responses were 0.23±0.08 (0.35±0.10) between 3-week weight and 3–6 week gain; 0.82±0.04 (0.58±0.08) between 3-week weight and 6-week weight; and 0.81±0.04 (0.97±0.04) between 3–6 week gain and 6-week weight. The genetic correlation between 3-week weight and 6-week weight was asymmetric with a greater correlated response for 3-week weight when selecting for 6-week weight (1.06) than vice versa (0.63).
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  • 13
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    Theoretical and applied genetics 59 (1981), S. 129-137 
    ISSN: 1432-2242
    Keywords: Selection ; Mice ; Feeding Efficiency ; Correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Selection was practised for improved feed efficiency (gain/feed intake) of mice on two alternative feeding regimes. In one set of lines animals were fed ad libitum, in the other set they were individually fed a fixed amount of feed (about 10% below the control ad libitum intake) which was not changed over generations. For each treatment, a pair of replicate lines (E) were selected on efficiency from 3–5 weeks of age for 8 generations and another pair (L) from 5–7 weeks for 7 generations. A control line was maintained for both E and L lines. In terminal generations mice from each line were tested on each feeding regime, and carcasses of ad libitum fed mice were analysed. The realized heritability (within families) for efficiency averaged 13%, without much variation over treatments. In the E lines efficiency increased by about 18% of the control mean and in the L lines by about 60%, although absolute changes were small, and responses were similar on the two feeding regimes. Weights at the start of test decreased in the E lines and increased in the L lines; weights at the end of test increased in both. When tested on the alternative regimes, no interactions were detected for live weights, weight gains or efficiency; selection under fixed intake led to the same increase in appetite as did that under ad libitum. There were no interactions for carcass composition. Selection for efficiency led to an increase in fatness on both selection regimes and both weight ranges.
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  • 14
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    Theoretical and applied genetics 51 (1978), S. 249-260 
    ISSN: 1432-2242
    Keywords: Mice ; Maternal Effects ; Body Weight ; Maturity ; Sex-linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Direct and maternal genetic effects were evaluated for maturing patterns of body weight in mice using a crossfostering design. Crossfostering was performed in one group using dams from populations selected for rapid growth rate (M16 and H6) and their reciprocal F1. crosses. A second crossfostering group consisted of dams from the respective control populations (ICR and C2) and their reciprocal F1. 's. Population differences were partitioned into direct and maternal effects due to genetic origin, correlated selection responses, heterosis and cytoplasmic or sex-linked effects. Degree of maturity was calculated at birth, 12, 21, 31 and 42 days of age by dividing body weight at each age by 63-day weight. Absolute and relative maturing rates were calculated in adjacent age intervals between birth and 63 days. Genetic origin effects (ICR vs. C2; M16 vs. H6) were significant for many maturity traits, with average direct being more important than average maternal genetic effects. In general, correlated responses to selection for maturity traits were larger in the M16 population (M16 vs. ICR) than in the H6 population (H6 vs. C2) and correlated responses in average direct effects were larger than average maternal effects. Positive correlated responses in average direct effects were found for relative maturing rates at all ages and for absolute maturing rates from 31 to 63 days. Apparent correlated responses in degree of maturity were negative for M16 and H6. However, further analysis suggested that the correlated response for degree of maturity in H6 may be positive at later ages and negative at earlier ages. Direct and maternal heterosis for degree of maturity was positive in the selected and control crosses. Absolute and relative maturing rates showed positive heterosis initially, followed by negative heterosis. Reciprocal differences due to the cytoplasm or sex-linkage were not important for patterns of maturity.
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  • 15
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    Theoretical and applied genetics 65 (1983), S. 17-23 
    ISSN: 1432-2242
    Keywords: Diallel cross ; Maternal effects ; Heterosis ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A genetic framework was developed for the interpretation of statistical parameters estimated from a diallel experiment among a fixed set of lines. These included average direct genetic, average maternal genetic, general combining ability, reciprocal, and line and specific direct and maternal heterotic effects. The genetic model is based on direct and maternal additive and dominance genetic effects as would be expected in animal species. The model assumes that dominance is the underlying basis of heterosis. As an example, litter size at birth was analyzed from a 5 × 5 diallel cross with mice.
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  • 16
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    Theoretical and applied genetics 55 (1979), S. 209-223 
    ISSN: 1432-2242
    Keywords: Maternal effects ; Body composition ; Selection ; Growth ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The effect of the postnatal maternal environment, simulated by rearing mice in litters of three, six or nine, on body weight and body composition was investigated in three lines of mice differing widely in growth rate. The lines were selected for high (H6) and low (L6) 6-week body weight while the control line was maintained by random selection. Body weight and weights and percentages of ether extract, water, ash and protein at 21, 42, 63 and 84 days were recorded. With few exceptions, there were positive correlated responses to selection in body weight and in weights of body components. At 21 and 42 days the correlated responses were larger in L6 mice than in H6 mice. Body weight and weights of body components were larger for mice reared in litters of three than for those reared in litters of nine. Also, mice reared in litters of six were intermediate in body weight and weights of some of the body components between those reared in litters of three and nine. Differences in body weight and weights of body components due to postnatal maternal environment were small by comparison with differences due to genetic line. There were significant line by maternal environment interactions in body weight at 21 days and in ether extract weight at 21 and 63 days. Line and maternal environment differences in percentages of body components did not follow any consistent trend. The results for percentages of body components were further complicated by line x maternal environment interactions. In general, both line and postnatal maternal environmental differences in percentages of body components diminished with age.
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  • 17
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    Theoretical and applied genetics 50 (1977), S. 179-184 
    ISSN: 1432-2242
    Keywords: Mice ; Feed Efficiency ; Body Composition ; Protein Content ; Selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary An examination was carried out of the feed intake, feed efficiency and body composition of selected and unselected mice. It was demonstrated that selected mice utilised food more economically, and, in total, produced more protein than the control animals. However, selection had a negative influence on the percentage content of protein and ash. Also, selection caused greater adiposity of selected females and a greater water content in the bodies of selected males (in %).
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  • 18
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    Theoretical and applied genetics 51 (1977), S. 119-125 
    ISSN: 1432-2242
    Keywords: Mice ; Cross-nursing Technique ; Body Weight ; Prenatal and Postnatal Maternal Influences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The cross-nursing technique was used to assess the relative importance of prenatal and postnatal maternal influences on growth in mice from an unselected population originated from a cross of four highly inbred strains. Body weights were studied at birth, 7-, 14-, 21- and 42-days, in addition to the weight gains between these ages and tail length at 21 and 42 days of age. At littering, each dam in each nursing set retained two of her own offspring and two were transfereed to each of the other dams in the set, so that each nursed litter contained six young representing three mothers. Prenatal influences accounted for 37, 15, 10, 11 and 13 % of the total variation in the respective body weights, while postnatal influences accounted for 0, 64, 65, 49 and 14% at the respective ages. In the case of weight gains, prenatal influences were responsible for 16, 4, 6 and 30%, while postnatal influences were responsible for 66, 66, 31 and 7% of the total variation in gain during the respective four periods examined. Apparently the individual weight gain from 7 to 14 days was a better measure of the lactational performance of the dam than individual 14-day weight. For tail length, prenatal influences accounted for 6 % and 4 % of the total variation in tail length at 21 and 42 days, respectively, while postnatal influences accounted for 60 % and 24 % at the respective ages. Generally, there was no indication of an important interaction between the nurse and the nursed young at any stage studied.
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  • 19
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    Theoretical and applied genetics 55 (1979), S. 279-284 
    ISSN: 1432-2242
    Keywords: Mating system ; Selection ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A reticulate mating system is described which was designed by the late R.A. Fisher to permit the introduction of new genetic variability into an improved stock by immigration. Analysis of part of a long-term experiment to alter the degree of dominance of the mutant Sd in mice using the system demonstrates a rapid response. Its applicability to stocks of animals of economic value is considered.
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  • 20
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    Theoretical and applied genetics 55 (1979), S. 57-64 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Growth curve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The weights of mice in lines selected for different combinations of high and low body weights at 5 and at 10 weeks of age were recorded from 3 to 21 weeks of age. The average growth curve for each line was computed using the Gompertz function. The growth curves of lines selected for high or low weight at a single age (ST lines) showed large differences in estimates of mature size and small differences in estimates of maturing rate, i.e. of the relative rate of growth to maturity. The growth curves of lines selected by independent culling for divergent combinations of deviations of opposite sign in 5- and 10-week weights (ICL lines) showed little difference in estimates of mature size and a large difference in estimates of maturing rate. The growth curves of lines selected by index for divergence in 5-week weight with no change in 10-week-weight or for divergence in 10-week-weight with no change in 5-week weight showed large differences in estimates of mature size and large differences in estimates of the maturing rate. The relationship between mature size and maturing rate was affected in different ways by the three types of selection.
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  • 21
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    Theoretical and applied genetics 57 (1980), S. 209-220 
    ISSN: 1432-2242
    Keywords: Mice ; Early puberty ; Litter size ; Selection ; Reproductive rate ; Pheromone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The influence of male-induced early puberty on female reproductive rate was determined in three lines of mice differing in litter size and body weight. The lines originated from a single base population and had undergone 20 generations of selection for the following criteria: large litter size at birth (L+), large litter size and small 6-week body weight (L+W−), or small litter size and large 6-week body weight (L−W+). Females were paired with a mature intact male of the same line at 3, 5 or 7 weeks of age. Mean mating age, averaged over lines, was 26.5 ± .3, 38.3 ± .3 and 52.7 ± .3 days. Exposure to a mature male accelerated female sexual maturation in each line. When contrasted with their sibs mated at a later age, early-pregnant females from each line exhibited a decline in one or more component of reproductive performance, suggesting that the physiological state of the very young female was not optimum for normal pregnancy. In comparisons of early and later mating ages, all three lines showed a decreased littering rate at first mating, number born alive, and individual birth weight of progeny adjusted for litter size; L+ and L+W− mice showed an increased perinatal mortality rate; L+ and L−W+ had a reduction in litter size at birth. When the L+, L+W− and L−W+ lines were compared with an unselected strain and a line selected for high postweaning gain in similar experiments, a genotype by environment interaction was apparent since all lines did not respond in a similar manner to early mating. The line ranking for litter size at birth for each age at male-exposure was L+〉L+W−〉L−W+, despite the significant line by age interaction. When litter size was adjusted by covariance for body weight at mating, the significant effects of age at male-exposure and line by age interaction were eliminated. All fertile females were remated after they had weaned their first litter to obtain information on litter size in parity two. Line differences in litter size at birth and number born alive were uniform across parities. An age by parity interaction was evident since the decreased fecundity at younger ages of male exposure in the L+ and L−W+ litters of parity one was not evident in parity two. Litter feed efficiency during first parity gestation was defined as litter birth weight divided by either cumulative feed intake of the dam from mating to parturition (GEI) or cumulative feed intake from weaning to parturition (GEII). The ranking of lines for GEI and GEH was L+〉 L+W−〉L−W+, but when feed efficiency was adjusted for littering rate, L+W− and L−W+ were not significantly different. With regard to age at mating, the ranking for GEI (7 wk 〉 5 wk 〉 3 wk) was reversed from GEII (3 wk 〉5 wk 〉 7 wk) and these significant differences were maintained after adjustment for littering rate.
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  • 22
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    Theoretical and applied genetics 54 (1979), S. 169-175 
    ISSN: 1432-2242
    Keywords: Mice ; Reciprocal crossing of lines ; Accumulated response to selection free of inbreeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Mass selection of mice was conducted in populations of various size for 16 generations. Each selected population (E) corresponded to an analogous unselected population (C). The experiment was conducted in three replicates. After the 16th generation the replicates of the selected and control lines were crossed. Reciprocal crossing within the control lines gave better results than reciprocal crossing of the selected lines, despite the fact that the selected mice were characterised by a higher inbreeding coefficient. Larger effects were also obtained when crossing smaller rather than larger populations. This result is understandable since the animals from the smaller populations were characterised by higher inbreeding coefficients. The effect of heterosis was higher upon crossing the control lines rather than the selected ones and this caused a decreased the response to selection in almost all the traits investigated.
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  • 23
    ISSN: 1420-9071
    Keywords: Mice ; glucan treatment ; Co60-irradiation ; stem cells, pluripotent ; granulocytes ; macrophages ; erythroid progenitor cells ; hemopoietic stomal cells ; hemopoiesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Glucan, a beta-1, 3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistantly exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage, and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.
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  • 24
    ISSN: 1573-0832
    Keywords: Cryptococcus ; Immunity ; Immunohistology ; Meningoencephalitis ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract An immunohistological study of L3T4(CD4)+ and LYT-2(CD8)+ lymphocytes, Mac-1(CD11b)+ monocytes and granulocytes in experimental murine cryptococcal meningoencephalitis was conducted. To assess the concomitant inflammatory reaction in an extracerebral site, livers were examined in parallel. Mice were infected i.v. withCryptococcus neoformans, group A/D, and organs were examined immunohistologically for CD4-, CD8- and monocyteand granulocyte-specific CD11b-phenotypic leukocytes over a period of 60 days. Intracerebrally, agglomerations of cryptococci formed pseudocysts that were surrounded by CD4+ and CD8+ lymphocytes at the end of the second week post-infection, followed by the invasion of monocytes and granulocytes into the lesions. After the fourth week post-infection, most of the invaded lesions were transformed into glious scars. Meningitis was usually marked and showed a homogenous distribution of CD4-, CD8- and CD11b-phenotypic cells, with a predominance of monocytes and CD4+ lymphocytes. Inflammatory infiltrates in the liver were found already 4 days post-infection. CD4+ lymphocytes and monocytes were distributed homogenously in the infiltrates, with a lower number of CD8+ lymphocytes being located rather in the periphery of the infiltrates. Comparing leukocyte kinetics in brain and liver, an important observation was the delayed immigration of immune cells at the intracerebral cryptococcal lesions as compared with the liver, and the different migration patterns of T-lymphocyte subgroups and macrophages. These results suggest that there are differential leukocyte migration patterns in the liver and brain following disseminated cryptococcosis. The immunological aspects of the observed leukocyte kinetics are discussed.
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  • 25
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    Behavior genetics 14 (1984), S. 1-19 
    ISSN: 1573-3297
    Keywords: Mice ; alcohol ; selective breeding ; pharmacogenetics ; biometrical genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract A classical Mendelian cross was derived from Long-Sleep (LS) and Short-Sleep (SS) mice, lines selectively bred for differences in response to hypnotic doses of ethanol (ETOH). Biometrical genetic procedures applied to the selection phenotype, namely, duration of the ETOH-induced loss of the righting reflex, suggest that a simple additive genetic system controls this depressant response. Sex differences were present in the Mendelian cross generations that had the longest duration responses. An estimate of the number of loci differentiated by the selection was nine. Blood ethanol levels at the time of regaining the righting reflex in the seven genotypes of the Mendelian cross showed that the selection operated solely by changing tissue sensitivity to ethanol.
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  • 26
    ISSN: 1573-3297
    Keywords: Mice ; ultrasonic calls ; infants ; individual differences ; signatures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Infant house mice, Mus musculus, produce ultrasonic calls that reliably lead to retrieval by adult mice. While individual differences in calls have been demonstrated both among and within species, the influences of age and sex on call characteristics have not been systematically investigated in mice. This study examined the influences of age, sex, and genotype (inbred versus hybrid) on the rate, length, and frequency characteristics of the calls of 486 male and female mice from 2 to 12 days of age. Rate of calling followed a shallow inverted U-shaped function across days. Call lengths decreased and call frequency characteristics increased, in a linear manner, with age. Females emitted fewer calls, with a smaller bandwidth, at some ages than males. Hybrid pups produced more calls of greater length and a lower frequency than inbred pups. These results indicate the presence of cues that could allow adult mice to behave differentially toward pups as a function of their age and sex.
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  • 27
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    Behavior genetics 26 (1996), S. 463-470 
    ISSN: 1573-3297
    Keywords: Mice ; agonistic behavior ; aggression ; homogeneous set ; standard tester ; social behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Though social behavior has not been overlooked by behavior geneticists, the number of studies is small when compared to those on individual traits. One reason for the neglect may be the difficulty of making connections between genes and social behaviors, which by definition involve the interaction of two or more organisms. Fuller and Hahn (1976) addressed this issue and described three means of establishing social groups that would facilitate genetic analysis. We survey the literature on agonistic behavior in mice from 1976 through 1994 and describe interesting uses of those three methods. One of those methods (the standard tester design) often employs a “noninteractive” social partner. We present data showing that the standard tester design may be more valuable when using an evocative and interactive standard tester.
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  • 28
    ISSN: 1573-3297
    Keywords: Mice ; ultrasounds ; ultrasonic calls ; infants ; diallel cross ; individual differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Ultrasonic calls produced by young mice reliably elicit investigation and retrieval by adults. While there are large individual differences in the characteristics of these calls, little work has been done to partition that variation. We completed a 4 × 4 diallel cross and Hayman analyses on several characteristics of these cries. The major result was the detection of directional dominance toward a higher rate of calling, longer calls, and calls of lower overall frequency with a greater bandwidth. Within the context of biometrical genetic theory, we conclude that calls with such characteristics may have important fitness value. Extending this idea, we propose that within the population sampled for this study (the animals of the four inbred strains and 12 F1 hybrid groups), the calls most effectively eliciting investigation and retrieval would be calls with the average hybrid values of the diallel cross.
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  • 29
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    Behavior genetics 25 (1995), S. 361-366 
    ISSN: 1573-3297
    Keywords: Mice ; aggression ; isolation-induced aggression ; predatory aggression ; selected lines ; genetic variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Male mice differing in their genetically determined disposition for isolation-induced intermale aggression were compared on behaviors related to predatory aggression. An ongoing sequence of selective breeding established high-aggressive (Turku Aggressive: TA) and low-aggressive (Turku Non-Aggressive: TNA) lines from an outbred Swiss albino foundation stock. The parental strain, designated the Normal (N) strain, has been kept as a control line and is bred without regard to aggressiveness. Testing consisted of dropping a live cricket into the home cage of the individually housed experimental mice. Results showed that the TA males displayed shorter latencies to attack and spent more time in chasing, attacking, and consuming crickets than did TNA and N males. The TNA males displayed significantly less predatory aggression than both the TA and N males. When brothers of the males tested for predatory aggression were tested for intermale aggression, a similarly significant effect of breeding line was obtained for the latency to attack. Testing consisted of placing an intact male mouse into the cage of the male to be tested. The results suggest that there may be parallels in genetic variation between intermale and predatory attacking.
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  • 30
    ISSN: 1432-0878
    Keywords: Key words: Skeletal muscle ; Regeneration ; Ageing ; Strain-specific muscle precursor replication ; Autoradiography ; Mice ; BALBc (SJL/J)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The patterns of skeletal muscle precursor cell replication after crush injury were compared by the use of autoradiographic techniques, in young (4-week-old) and old (39-week-old) BALBc and SJL/J mice. Similar comparisons were made between cut and crush lesions in old BALBc muscle. Muscle precursor cell replication commenced at 18–24 h after injury in both young and old muscles from both strains of mice. In young BALBc muscle the peak of myogenic activity at 60 h was 36 h earlier than in old mice. SJL/J muscle responded more rapidly than did BALBc: in young SJL/J the peak myogenic activity was at 46 h (14 h earlier than in young BALBc muscle), and in old SJL/J muscle the peak activity at 72 h was 24 h earlier than in old BALBc muscle. In all mice (both young and old) myogenic cell replication was substantially reduced by 120 h after injury. A comparison of the timing of muscle precursor cell replication in cut and crush lesions in old BALBc mice revealed a more rapid response in the cut lesion; this difference between the lesions is comparable with data from identical lesions in 6–8-week-old BALBc mice (McGeachie and Grounds 1987). However, the peak of myogenic replication in the older mice in the present study was some 26–36 h later than in the younger 6–8-week-old mice. These experiments show that, whilst muscle precursor cell replication commences at approximately the same time (about 24 h) after injury in young and old mice, the peak level of activity is delayed by some 24–36 h in old mice. In addition, the SJL/J mouse strain responds more rapidly and prolifically to muscle injury than does the BALBc strain.
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  • 31
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    Parasitology research 61 (1980), S. 179-185 
    ISSN: 1432-1955
    Keywords: Trypanosoma cruzi ; Delayed hypersensitivity ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Delayed type hypersensitivity reactions (DTH) to DNFB in C3H (susceptible) and (CBA×C57B1/10)F1 (resistant) mice were not impaired inTrypanosoma cruzi strain Y infections. Mice were infected IP with 100 parasites and sensitized or challenged 11 days after infection at the peak of parasitaemia. DTH reactions were found to be enhanced in C3H infected mice.
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  • 32
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    Parasitology research 61 (1980), S. 243-247 
    ISSN: 1432-1955
    Keywords: Hymenolepis microstoma ; Mice ; Orchiectomy ; Ovariectomy ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Gonadectomy or sex of the host had no effect on the mean dry weight ofHymenolepis microstoma examined on day 12 postinfection (p.i.). However, on day 20 p.i. worms from intact or sham-operated male mice were significantly heavier than those recovered from the corresponding groups of female hosts. Orchiectomy of hosts lowered the average weight of these older worms, but ovariectomy had no effect.
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  • 33
    ISSN: 1432-1955
    Keywords: Trypanosoma cruzi ; Immunosuppression ; Immunenhancement ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract (CBA×C57 B1/10)F1 mice infected intraperitoneally with 100 parasites ofTrypanosoma cruzi strain Y developed an infection with acute and chronic phases. Humoral suppression to sheep red blood cells was evident in both phases but enhancement of the response was achieved only at the beginning of the infection. A mitogen secreted by the parasite could explain both phenomenons.
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  • 34
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    Cell & tissue research 238 (1984), S. 643-647 
    ISSN: 1432-0878
    Keywords: Binucleate cells ; Flow cytometry ; Hepatocytes ; Polyploidy pattern ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Preparative and mathematical procedures are presented for the investigation of the ploidy pattern of liver cells. The DNA content of enzymatically-isolated liver cells and of nuclei was measured by flow cytometry. The true DNA content could not be measured directly due to superposition of statistical coincidences (demanding “first mode correction”) and incomplete separation of the nuclei in binucleate hepatocytes (demanding “second mode correction”). The statistical coincidences (caused by simultaneous measurement of two or more particles or subsequent reaggregation of particles) were corrected by splitting the “unnatural” i.e., aneuploid DNA content, and classifying it with the normal ploidy classes. In addition, the higher normal ploidy classes were reduced by the proportion of the measured coincidences in favour of the lower ones. The second mode correction applied to nuclear distributions only. It is a probability calculation based on counting nuclear pairs on microscope slides, and resulted in a 10% increase of diploid nuclei and a larger standard deviation between the age groups. 8c and 16c values were reduced. The tetraploid values were unchanged.
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  • 35
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    Cell & tissue research 221 (1981), S. 371-383 
    ISSN: 1432-0878
    Keywords: Catecholamines ; Chromaffin cells ; Nerve endings ; Adrenal gland ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Light-microscopic autoradiography has revealed characteristic labelling patterns in adrenal medullary cells following the intravenous administration of different catecholamines. The uptake patterns for [3H] dopa, [3H] dopamine, [3H] noradrenaline and [3H] adrenaline have been compared. In all cases A cells were more active than NA cells and cells situated in the zone nearest the cortex demonstrated a markedly higher rate of uptake than central cells. It was concluded that adjacent chromaffin cells with very similar morphology may differ as much as 50 fold in their capacities to incorporate exogenous amines. The adrenergic nature of the innervation of the vessels of the adrenal cortex and capsule in the mouse was confirmed.
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  • 36
    ISSN: 1432-0878
    Keywords: Glucocorticoids ; Bone growth retardation ; Chondrocytes ; Rehabilitation ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immature A/J mice were treated for up to 7 weeks with intermittent doses of triamcinolone hexacetonide and were thereafter allowed to recover for 7 weeks. Qualitative and quantitative morphological measurements were performed on the epiphyseal cartilage plate and diaphyseal bone of the humerus. By the third injection significant structural changes were noted in the cartilaginous tissue followed by a complete cessation of bone growth. The hormonal inhibitory effect on long bone growth lasted throughout the experimental period. However, at the end of the recovery period the length of the humerus was 96% of the normal. In contrast, the humeral width at midshaft and the width of its medullary cavity revealed slower recovery, achieving only 80% of the control values. Following rehabilitation, the growth of experimental epiphyseal plates exceeded that of nontreated animals as their width and the number of hypertrophic chondrocytes were 131% and 125% of their controls respectively. Thus, in A/J mice (a highly susceptible inbred strain of mice) intermittent (every four days) administration of a long-acting corticosteroid hormone arrested endochondral and periosteal bone formation; the former, however, underwent full recovery following the termination of the hormonal treatment.
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  • 37
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    Publication Date: 2002-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, John H -- Elledge, Stephen J -- New York, N.Y. -- Science. 2002 Sep 13;297(5588):1822-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228708" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/metabolism ; BRCA2 Protein/*chemistry/*metabolism ; Binding Sites ; Breast Neoplasms/genetics ; Crystallography, X-Ray ; DNA/*metabolism ; DNA Damage ; *DNA Repair ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/metabolism ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Predisposition to Disease ; Humans ; Mice ; Ovarian Neoplasms/genetics ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rad51 Recombinase ; Rats ; Recombination, Genetic ; Replication Protein A
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 38
    Publication Date: 2002-04-16
    Description: Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I antigens, preventing attack against healthy cells. Mouse cytomegalovirus (MCMV) encodes an MHC-like protein (m157) that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice. In MCMV-resistant mice, this viral protein engages a related activating receptor (Ly49H) and confers host protection. These activating and inhibitory receptors are highly homologous, suggesting the possibility that one evolved from the other in response to selective pressure imposed by the pathogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arase, Hisashi -- Mocarski, Edward S -- Campbell, Ann E -- Hill, Ann B -- Lanier, Lewis L -- AI30363/AI/NIAID NIH HHS/ -- CA89294/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 May 17;296(5571):1323-6. Epub 2002 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11950999" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Antigens, Ly/chemistry/genetics/*immunology/metabolism ; Cell Line ; Coculture Techniques ; Disease Susceptibility ; Evolution, Molecular ; Herpesviridae Infections/*immunology ; Histocompatibility Antigens Class I/immunology ; Hybridomas ; Immunity, Innate ; Interferon-gamma/biosynthesis ; Killer Cells, Natural/*immunology ; Lectins, C-Type ; Ligands ; Lymphocyte Activation ; Membrane Glycoproteins/chemistry/genetics/*immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Muromegalovirus/genetics/*immunology/metabolism ; NK Cell Lectin-Like Receptor Subfamily A ; Protein Binding ; Receptors, Immunologic/chemistry/genetics/*immunology/metabolism ; Receptors, NK Cell Lectin-Like ; Recombinant Fusion Proteins/metabolism ; Transfection ; Viral Proteins/chemistry/genetics/*immunology/metabolism
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  • 39
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 40
    Publication Date: 2002-07-13
    Description: Full-length poliovirus complementary DNA (cDNA) was synthesized by assembling oligonucleotides of plus and minus strand polarity. The synthetic poliovirus cDNA was transcribed by RNA polymerase into viral RNA, which translated and replicated in a cell-free extract, resulting in the de novo synthesis of infectious poliovirus. Experiments in tissue culture using neutralizing antibodies and CD155 receptor-specific antibodies and neurovirulence tests in CD155 transgenic mice confirmed that the synthetic virus had biochemical and pathogenic characteristics of poliovirus. Our results show that it is possible to synthesize an infectious agent by in vitro chemical-biochemical means solely by following instructions from a written sequence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cello, Jeronimo -- Paul, Aniko V -- Wimmer, Eckard -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1016-8. Epub 2002 Jul 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12114528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Capsid/metabolism ; Cell-Free System ; DNA, Complementary/*chemical synthesis/genetics ; DNA-Directed RNA Polymerases/genetics ; Female ; *Genome, Viral ; HeLa Cells ; Humans ; Male ; *Membrane Proteins ; Mice ; Mice, Transgenic ; Neutralization Tests ; Poliomyelitis/virology ; *Poliovirus/genetics/immunology/pathogenicity/physiology ; Promoter Regions, Genetic ; Protein Biosynthesis ; RNA, Viral/*chemical synthesis/genetics/physiology ; Receptors, Virus/genetics/immunology/metabolism ; Transcription, Genetic ; Viral Plaque Assay ; Viral Proteins ; Virulence ; Virus Replication
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 41
    Publication Date: 2002-05-04
    Description: There is a relation between stress and alcohol drinking. We show that the corticotropin-releasing hormone (CRH) system that mediates endocrine and behavioral responses to stress plays a role in the control of long-term alcohol drinking. In mice lacking a functional CRH1 receptor, stress leads to enhanced and progressively increasing alcohol intake. The effect of repeated stress on alcohol drinking behavior appeared with a delay and persisted throughout life. It was associated with an up-regulation of the N-methyl-d-aspartate receptor subunit NR2B. Alterations in the CRH1 receptor gene and adaptional changes in NR2B subunits may constitute a genetic risk factor for stress-induced alcohol drinking and alcoholism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sillaber, Inge -- Rammes, Gerhard -- Zimmermann, Stephan -- Mahal, Beatrice -- Zieglgansberger, Walter -- Wurst, Wolfgang -- Holsboer, Florian -- Spanagel, Rainer -- New York, N.Y. -- Science. 2002 May 3;296(5569):931-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. sillaber@mpipsykl.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988580" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; *Alcohol Drinking ; Alcoholism/*etiology/genetics ; Animals ; Brain/metabolism ; Corticotropin-Releasing Hormone/physiology ; Ethanol/blood ; Female ; Hippocampus/physiology ; In Vitro Techniques ; Male ; Mice ; Mice, Knockout ; Models, Animal ; Mutation ; Receptors, AMPA/metabolism ; Receptors, Corticotropin-Releasing Hormone/*genetics/*physiology ; Receptors, Kainic Acid/metabolism ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Signal Transduction ; Stress, Physiological/physiopathology ; Stress, Psychological/*physiopathology ; Up-Regulation
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gura, Trisha -- New York, N.Y. -- Science. 2003 Feb 7;299(5608):849-52.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12574616" target="_blank"〉PubMed〈/a〉
    Keywords: Agouti-Related Protein ; Animals ; Anti-Obesity Agents/adverse effects/pharmacology/*therapeutic use ; Appetite/drug effects ; Arcuate Nucleus of Hypothalamus/metabolism ; Ciliary Neurotrophic Factor/therapeutic use ; Clinical Trials as Topic ; Cyclobutanes/adverse effects/therapeutic use ; Energy Intake ; Ghrelin ; Humans ; Hunger/drug effects ; Intercellular Signaling Peptides and Proteins ; Lactones/adverse effects/therapeutic use ; Leptin/metabolism/therapeutic use ; Mice ; Nerve Tissue Proteins/adverse effects/therapeutic use ; Neurons/metabolism ; Neuropeptide Y/metabolism/pharmacology ; Obesity/*drug therapy/metabolism ; Peptide Fragments ; Peptide Hormones/metabolism/pharmacology ; Peptide YY/metabolism/pharmacology ; Phentermine/adverse effects/therapeutic use ; Proteins/metabolism ; Receptors, Corticotropin/metabolism ; Receptors, Melanocortin ; Weight Loss ; alpha-MSH/metabolism
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Eliot -- New York, N.Y. -- Science. 2002 May 17;296(5571):1212.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12016275" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Drug Industry/legislation & jurisprudence ; Drug Screening Assays, Antitumor ; Mice ; *Mice, Transgenic ; National Institutes of Health (U.S.)/legislation & jurisprudence ; *Neoplasms, Experimental ; *Patents as Topic ; United States ; Universities/legislation & jurisprudence
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-02-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beckman, Mary -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):782.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823614" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression ; Animals ; *Behavior, Animal ; Cues ; Female ; Male ; Membrane Proteins/*genetics/*physiology ; Mice ; Mice, Knockout ; Neurons/physiology ; Pheromones/*physiology ; Sex Characteristics ; *Sexual Behavior, Animal ; TRPC Cation Channels ; Vomeronasal Organ/*innervation/physiology
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-09-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beckman, Mary -- New York, N.Y. -- Science. 2002 Sep 6;297(5587):1626-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215618" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/*immunology ; Arthritis, Rheumatoid/immunology ; Autoantibodies/immunology ; Humans ; Joints/*immunology ; Mast Cells/immunology ; Mice
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  • 46
    Publication Date: 2003-08-09
    Description: Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles. The cause of ALS is unknown, and there is no effective therapy. Neurotrophic factors are candidates for therapeutic evaluation in ALS. Although chronic delivery of molecules to the central nervous system has proven difficult, we recently discovered that adeno-associated virus can be retrogradely transported efficiently from muscle to motor neurons of the spinal cord. We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaspar, Brian K -- Llado, Jeronia -- Sherkat, Nushin -- Rothstein, Jeffrey D -- Gage, Fred H -- AG12992/AG/NIA NIH HHS/ -- AG21876/AG/NIA NIH HHS/ -- NS33958/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):839-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907804" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/pathology/physiopathology/*therapy ; Animals ; Apoptosis ; Base Sequence ; Caspase 9 ; Caspases/metabolism ; Cell Count ; Dependovirus/*genetics ; Disease Models, Animal ; Disease Progression ; Gene Transfer Techniques ; *Genetic Therapy ; *Genetic Vectors/administration & dosage ; Glial Cell Line-Derived Neurotrophic Factor ; Green Fluorescent Proteins ; Insulin-Like Growth Factor I/*genetics ; Luminescent Proteins/genetics ; Male ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Motor Neurons/pathology/virology ; Muscle, Skeletal/virology ; Nerve Growth Factors/genetics ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Random Allocation ; Spinal Cord/chemistry/pathology/virology ; Superoxide Dismutase/genetics/metabolism ; Ubiquitin/analysis
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  • 47
    Publication Date: 2003-05-06
    Description: Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hafezparast, Majid -- Klocke, Rainer -- Ruhrberg, Christiana -- Marquardt, Andreas -- Ahmad-Annuar, Azlina -- Bowen, Samantha -- Lalli, Giovanna -- Witherden, Abi S -- Hummerich, Holger -- Nicholson, Sharon -- Morgan, P Jeffrey -- Oozageer, Ravi -- Priestley, John V -- Averill, Sharon -- King, Von R -- Ball, Simon -- Peters, Jo -- Toda, Takashi -- Yamamoto, Ayumu -- Hiraoka, Yasushi -- Augustin, Martin -- Korthaus, Dirk -- Wattler, Sigrid -- Wabnitz, Philipp -- Dickneite, Carmen -- Lampel, Stefan -- Boehme, Florian -- Peraus, Gisela -- Popp, Andreas -- Rudelius, Martina -- Schlegel, Juergen -- Fuchs, Helmut -- Hrabe de Angelis, Martin -- Schiavo, Giampietro -- Shima, David T -- Russ, Andreas P -- Stumm, Gabriele -- Martin, Joanne E -- Fisher, Elizabeth M C -- New York, N.Y. -- Science. 2003 May 2;300(5620):808-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730604" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anterior Horn Cells/pathology ; Apoptosis ; *Axonal Transport ; Cell Differentiation ; Cell Movement ; Central Nervous System/embryology ; Chromosome Mapping ; Dimerization ; Dyneins/chemistry/*genetics/*physiology ; Female ; Ganglia, Spinal/pathology ; Golgi Apparatus/metabolism/ultrastructure ; Heterozygote ; Homozygote ; Lewy Bodies/pathology ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Motor Neuron Disease/*genetics/pathology/physiopathology ; Motor Neurons/*physiology/ultrastructure ; Mutation ; Mutation, Missense ; *Nerve Degeneration ; Peptide Fragments/metabolism ; Phenotype ; Point Mutation ; Spinal Nerves/growth & development ; Tetanus Toxin/metabolism
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  • 48
    Publication Date: 2002-02-09
    Description: The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gadek, T R -- Burdick, D J -- McDowell, R S -- Stanley, M S -- Marsters, J C Jr -- Paris, K J -- Oare, D A -- Reynolds, M E -- Ladner, C -- Zioncheck, K A -- Lee, W P -- Gribling, P -- Dennis, M S -- Skelton, N J -- Tumas, D B -- Clark, K R -- Keating, S M -- Beresini, M H -- Tilley, J W -- Presta, L G -- Bodary, S C -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1086-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834839" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/pharmacology ; Cyclosporine/pharmacology ; Dermatitis, Irritant/drug therapy ; Dinitrofluorobenzene ; Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Immunosuppressive Agents/chemical synthesis/chemistry/metabolism/*pharmacology ; Intercellular Adhesion Molecule-1/chemistry/*immunology/*metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Mutagenesis ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thiophenes/*chemical synthesis/chemistry/metabolism/*pharmacology ; beta-Alanine/analogs & derivatives/*chemical ; synthesis/chemistry/metabolism/*pharmacology
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  • 49
    Publication Date: 2002-11-16
    Description: Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid follicles (ILFs) associated with a 100-fold expansion of anaerobic flora in the small intestine. Reduction of bacterial flora by antibiotic treatment of AID-/- mice abolished ILF hyperplasia as well as the germinal center enlargement seen in secondary lymphoid tissues. Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fagarasan, Sidonia -- Muramatsu, Masamichi -- Suzuki, Keiichiro -- Nagaoka, Hitoshi -- Hiai, Hiroshi -- Honjo, Tasuku -- New York, N.Y. -- Science. 2002 Nov 15;298(5597):1424-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12434060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents ; B-Lymphocytes/immunology ; Bacteria, Aerobic/*growth & development ; Bacteria, Anaerobic/*growth & development ; Cell Division ; Colony Count, Microbial ; Cytidine Deaminase/genetics/*metabolism ; Dendritic Cells, Follicular/immunology ; Drug Therapy, Combination/pharmacology ; Genes, Immunoglobulin ; Germinal Center/immunology ; Homeostasis ; Hyperplasia ; Immunization ; Immunoglobulin Class Switching ; Immunoglobulin Variable Region/genetics ; Intestine, Small/immunology/*microbiology ; Lymphocyte Activation ; Lymphoid Tissue/immunology/*pathology ; Metronidazole/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Peyer's Patches/pathology ; Somatic Hypermutation, Immunoglobulin ; T-Lymphocytes/immunology
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  • 50
    Publication Date: 2002-12-10
    Description: The formation and patterning of mesoderm during mammalian gastrulation require the activity of Nodal, a secreted mesoderm-inducing factor of the transforming growth factor-beta (TGF-beta) family. Here we show that the transcriptional corepressor DRAP1 has a very specific role in regulation of Nodal activity during mouse embryogenesis. We find that loss of Drap1 leads to severe gastrulation defects that are consistent with increased expression of Nodal and can be partially suppressed by Nodal heterozygosity. Biochemical studies indicate that DRAP1 interacts with and inhibits DNA binding by the winged-helix transcription factor FoxH1 (FAST), a critical component of a positive feedback loop for Nodal activity. We propose that DRAP1 limits the spread of a morphogenetic signal by down-modulating the response to the Nodal autoregulatory loop.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iratni, Rabah -- Yan, Yu-Ting -- Chen, Canhe -- Ding, Jixiang -- Zhang, Yi -- Price, Sandy M -- Reinberg, Danny -- Shen, Michael M -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):1996-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry, Division of Nucleic Acids Enzymology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471260" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Cell Line ; Crosses, Genetic ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; *Embryonic and Fetal Development ; Female ; Forkhead Transcription Factors ; Gastrula/*physiology ; Gene Expression Regulation, Developmental ; Gene Targeting ; Heterozygote ; In Situ Hybridization ; Left-Right Determination Factors ; Male ; Mesoderm/cytology/physiology ; Mice ; Morphogenesis ; Mutation ; Nodal Protein ; Phenotype ; Protein Binding ; RNA Interference ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; *Signal Transduction ; Transcription Factors/metabolism ; Transforming Growth Factor beta/genetics/*metabolism
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  • 51
    Publication Date: 2003-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Martin -- Bristow, Robert -- Glazer, Peter -- Hill, Richard -- McBride, William -- McKenna, Gillies -- Muschel, Ruth -- New York, N.Y. -- Science. 2003 Dec 12;302(5652):1894; author reply 1894.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14671275" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Disease Models, Animal ; Endothelium, Vascular/*pathology/radiation effects ; Melanoma, Experimental/blood supply/immunology/pathology/*radiotherapy ; Mice ; Radiation Tolerance ; Sphingomyelin Phosphodiesterase/genetics/metabolism
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  • 52
    Publication Date: 2002-06-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copeland, Neal G -- Jenkins, Nancy A -- O'Brien, Stephen J -- New York, N.Y. -- Science. 2002 May 31;296(5573):1617-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, 21702, USA. copeland@ncifcrf.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12040165" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Biological Evolution ; Chromosome Aberrations ; Chromosomes/*genetics ; Chromosomes, Human/genetics ; Computational Biology ; Conserved Sequence ; Evolution, Molecular ; Gene Duplication ; Gene Rearrangement ; Genes ; Genome ; *Genome, Human ; Genomics ; Humans ; Mice ; Mice, Inbred Strains/*genetics ; Multigene Family ; *Sequence Analysis, DNA ; Species Specificity ; Synteny
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  • 53
    Publication Date: 2003-07-05
    Description: Animal behavior is synchronized to the 24-hour light:dark (LD) cycle by regulatory programs that produce circadian fluctuations in gene expression throughout the body. In mammals, the transcription factor CLOCK controls circadian oscillation in the suprachiasmatic nucleus of the brain; its paralog, neuronal PAS domain protein 2 (NPAS2), performs a similar function in other forebrain sites. To investigate the role of NPAS2 in behavioral manifestations of circadian rhythm, we studied locomotor activity, sleep patterns, and adaptability to both light- and restricted food-driven entrainment in NPAS2-deficient mice. Our results indicate that NPAS2 plays a substantive role in maintaining circadian behaviors in normal LD and feeding conditions and that NPAS2 is critical for adaptability to food restriction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dudley, Carol A -- Erbel-Sieler, Claudia -- Estill, Sandi Jo -- Reick, Martin -- Franken, Paul -- Pitts, SiNae -- McKnight, Steven L -- 37919/PHS HHS/ -- 4R37 MH59388/MH/NIMH NIH HHS/ -- 5T3DK07328/DK/NIDDK NIH HHS/ -- HL 64148/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):379-83. Epub 2003 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12843397" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Behavior, Animal ; Biological Clocks/*physiology ; Body Weight ; CLOCK Proteins ; Circadian Rhythm/*physiology ; Crosses, Genetic ; Darkness ; Eating ; Electroencephalography ; Electromyography ; Female ; Food ; Gene Targeting ; Light ; Male ; Mice ; Mice, Inbred C57BL ; *Motor Activity ; Nerve Tissue Proteins/genetics/*physiology ; Prosencephalon/physiology ; *Sleep ; Suprachiasmatic Nucleus/physiology ; Trans-Activators/genetics/physiology ; Transcription Factors/genetics/*physiology
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  • 54
    Publication Date: 2003-03-01
    Description: Recent progress in the science of aging is driven largely by the use of model systems, ranging from yeast and nematodes to mice. These models have revealed conservation in genetic pathways that balance energy production and its damaging by-products with pathways that preserve somatic maintenance. Maintaining genome integrity has emerged as a major factor in longevity and cell viability. Here we discuss the use of mouse models with defects in genome maintenance for understanding the molecular basis of aging in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hasty, Paul -- Campisi, Judith -- Hoeijmakers, Jan -- van Steeg, Harry -- Vijg, Jan -- AG17242/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1355-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78245, USA. hastye@uthscsa.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610296" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging/genetics ; Aging, Premature/*genetics ; Animals ; Apoptosis ; Cell Aging ; *DNA Damage ; DNA Helicases/genetics/metabolism ; *DNA Repair/genetics ; Exodeoxyribonucleases ; *Genome ; Genome, Human ; Humans ; Longevity/genetics ; Mice ; Mutation ; Reactive Oxygen Species/metabolism ; RecQ Helicases ; Syndrome ; Telomere/physiology ; Transcription, Genetic
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  • 55
    Publication Date: 2003-04-12
    Description: Rapid turnover of the tumor suppressor protein p53 requires the MDM2 ubiquitin ligase, and both interact with p300-CREB-binding protein transcriptional coactivator proteins. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grossman, Steven R -- Deato, Maria E -- Brignone, Chrystelle -- Chan, Ho Man -- Kung, Andrew L -- Tagami, Hideaki -- Nakatani, Yoshihiro -- Livingston, David M -- CA15751/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):342-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690203" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/metabolism ; Animals ; Catalysis ; Cells, Cultured ; E1A-Associated p300 Protein ; Embryo, Mammalian ; Fibroblasts/metabolism ; Humans ; Ligases/antagonists & inhibitors/metabolism ; Mice ; Nuclear Proteins/antagonists & inhibitors/*metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; Trans-Activators/antagonists & inhibitors/*metabolism ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism
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  • 56
    Publication Date: 2003-04-26
    Description: The active-site cysteine of peroxiredoxins is selectively oxidized to cysteine sulfinic acid during catalysis, which leads to inactivation of peroxidase activity. This oxidation was thought to be irreversible. However, by metabolic labeling of mammalian cells with 35S, we show that the sulfinic form of peroxiredoxin I, produced during the exposure of cells to H2O2, is rapidly reduced to the catalytically active thiol form. The mammalian cells' ability to reduce protein sulfinic acid might serve as a mechanism to repair oxidatively damaged proteins or represent a new type of cyclic modification by which the function of various proteins is regulated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woo, Hyun Ae -- Chae, Ho Zoon -- Hwang, Sung Chul -- Yang, Kap-Seok -- Kang, Sang Won -- Kim, Kanghwa -- Rhee, Sue Goo -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):653-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cell Signaling Research and Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12714748" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalysis ; Cell Line ; Cycloheximide/pharmacology ; Cysteine/*analogs & derivatives/*metabolism ; Dimerization ; HeLa Cells ; Humans ; Hydrogen Peroxide/*metabolism ; Methionine/metabolism ; Mice ; Neurotransmitter Agents ; Oxidation-Reduction ; Peroxidases/chemistry/*metabolism ; Peroxiredoxins ; Protein Synthesis Inhibitors/pharmacology ; Spectrometry, Mass, Electrospray Ionization ; Sulfhydryl Compounds/metabolism ; Sulfinic Acids/metabolism ; Tumor Cells, Cultured
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  • 57
    Publication Date: 2003-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eden, Amir -- Gaudet, Francois -- Waghmare, Alpana -- Jaenisch, Rudolf -- CA87869/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 18;300(5618):455.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12702868" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/*genetics/physiology ; DNA (Cytosine-5-)-Methyltransferase/genetics/metabolism ; *DNA Methylation ; Fibroblasts/metabolism ; Genes, Neurofibromatosis 1 ; Genes, p53 ; Humans ; *Loss of Heterozygosity ; Mice ; Mutation ; Neoplasms/genetics ; Recombination, Genetic ; Sarcoma/*genetics ; Soft Tissue Neoplasms/*genetics
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-07-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heintz, Nathaniel -- New York, N.Y. -- Science. 2003 Jul 4;301(5629):59-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Rockefeller University, New York, NY 10021, USA. heintz@rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12843383" target="_blank"〉PubMed〈/a〉
    Keywords: 14-3-3 Proteins ; Amino Acid Substitution ; Animals ; Ataxin-1 ; Ataxins ; Cell Nucleus/metabolism ; Disease Progression ; Mice ; Mice, Transgenic ; Mutation ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Nuclear Proteins/*chemistry/genetics/*metabolism ; Peptides ; Phosphorylation ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Purkinje Cells/metabolism/ultrastructure ; Signal Transduction ; Spinocerebellar Ataxias/etiology/genetics/pathology/*physiopathology ; *Trinucleotide Repeat Expansion ; Tyrosine 3-Monooxygenase/*metabolism
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  • 59
    Publication Date: 2003-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rajagopal, Jayaraj -- Anderson, William J -- Kume, Shoen -- Martinez, Olga I -- Melton, Douglas A -- New York, N.Y. -- Science. 2003 Jan 17;299(5605):363.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12532008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Apoptosis ; Cell Differentiation ; Cell Line ; Embryo, Mammalian/*cytology ; Humans ; Insulin/*analysis/genetics/immunology/*metabolism ; Islets of Langerhans/*cytology/metabolism ; Mice ; Microscopy, Confocal ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells/*cytology/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 60
    Publication Date: 2003-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nobrega, Marcelo A -- Ovcharenko, Ivan -- Afzal, Veena -- Rubin, Edward M -- HL66728/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 17;302(5644):413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14563999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura/genetics ; Base Sequence ; Conserved Sequence ; *DNA, Intergenic ; *Drosophila Proteins ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Gene Expression Regulation ; Genes, Reporter ; Humans ; Introns ; Mice ; Mice, Transgenic ; Nuclear Proteins/*genetics ; Synteny ; Takifugu/genetics ; Tetraodontiformes/genetics ; Xenopus/genetics ; Zebrafish/genetics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 61
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-09-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yewdell, Jonathan W -- New York, N.Y. -- Science. 2003 Sep 5;301(5638):1334-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0440, USA. jyewdell@nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12958347" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; Codon ; Cysteine Endopeptidases/metabolism ; Epstein-Barr Virus Nuclear Antigens/chemistry/*genetics/*immunology/metabolism ; Herpesvirus 4, Human/physiology ; Histocompatibility Antigens Class I/*immunology ; Humans ; Mice ; Mice, Transgenic ; Multienzyme Complexes/metabolism ; Peptides/genetics/*immunology/*metabolism ; Proteasome Endopeptidase Complex ; *Protein Biosynthesis ; Reading Frames ; Ribosomes/metabolism ; Self Tolerance ; Virus Latency
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  • 62
    Publication Date: 2003-08-09
    Description: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santarelli, Luca -- Saxe, Michael -- Gross, Cornelius -- Surget, Alexandre -- Battaglia, Fortunato -- Dulawa, Stephanie -- Weisstaub, Noelia -- Lee, James -- Duman, Ronald -- Arancio, Ottavio -- Belzung, Catherine -- Hen, Rene -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):805-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907793" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Antidepressive Agents/*pharmacology ; Antidepressive Agents, Second-Generation/pharmacology ; Antidepressive Agents, Tricyclic/pharmacology ; Behavior, Animal/*drug effects ; Cell Division/drug effects/radiation effects ; Conditioning (Psychology) ; Dentate Gyrus/cytology/drug effects/physiology ; Fear ; Feeding Behavior/drug effects ; Fluoxetine/*pharmacology ; Grooming/drug effects ; Hippocampus/cytology/drug effects/*physiology/radiation effects ; Long-Term Potentiation/radiation effects ; Male ; Mice ; Mice, Knockout ; Neurons/drug effects/*physiology ; Receptors, Serotonin/genetics/metabolism ; Receptors, Serotonin, 5-HT1 ; Stress, Physiological/drug therapy/physiopathology ; Synaptic Transmission/radiation effects
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  • 63
    Publication Date: 2003-07-19
    Description: Direct quantification of biomolecular interaction by single-molecule force spectroscopy has evolved into a powerful tool for materials and life sciences. We introduce an approach in which the unbinding forces required to break intermolecular bonds are measured in a differential format by comparison with a known reference bond (here, a short DNA duplex). In addition to a marked increase in sensitivity and force resolution, which enabled us to resolve single-base pair mismatches, this concept allows for highly specific parallel assays. This option was exploited to overcome cross-reactions of antibodies in a protein biochip application.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Albrecht, Christian -- Blank, Kerstin -- Lalic-Multhaler, Mio -- Hirler, Siegfried -- Mai, Thao -- Gilbert, Ilka -- Schiffmann, Susanne -- Bayer, Tom -- Clausen-Schaumann, Hauke -- Gaub, Hermann E -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):367-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nanotype GmbH, Lochhamer Schlag 12, 82166 Grafelfing, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies ; *Base Pair Mismatch ; *Biosensing Techniques ; Carbocyanines ; Cross Reactions ; *DNA/chemistry/genetics/metabolism ; Dimethylpolysiloxanes ; Fluorescence ; Fluorescent Dyes ; Glass ; Humans ; Immunoassay ; Interleukin-5/analysis/immunology ; Mice ; Microscopy, Atomic Force ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/chemistry/metabolism ; *Oligonucleotide Array Sequence Analysis ; *Protein Array Analysis ; Protein Binding ; Silicones ; Temperature ; Thermodynamics
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  • 64
    Publication Date: 2003-09-27
    Description: The classical paradigm for dendritic cell function derives from the study of Langerhans cells, which predominate within skin epidermis. After an encounter with foreign agents, Langerhans cells are thought to migrate to draining lymph nodes, where they initiate T cell priming. Contrary to this, we show here that infection of murine epidermis by herpes simplex virus did not result in the priming of virus-specific cytotoxic T lymphocytes by Langerhans cells. Rather, the priming response required a distinct CD8alpha+ dendritic cell subset. Thus, the traditional view of Langerhans cells in epidermal immunity needs to be revisited to accommodate a requirement for other dendritic cells in this response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allan, Rhys S -- Smith, Chris M -- Belz, Gabrielle T -- van Lint, Allison L -- Wakim, Linda M -- Heath, William R -- Carbone, Francis R -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1925-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512632" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigens, CD/analysis ; Antigens, CD8/*analysis ; Antigens, Viral/immunology ; Cell Separation ; Chimera ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Epidermis/*immunology ; H-2 Antigens/analysis/immunology ; Herpes Simplex/*immunology ; Herpesvirus 1, Human/*immunology ; Histocompatibility Antigens Class II/analysis ; Langerhans Cells/*immunology ; Lectins, C-Type/analysis ; Lymph Nodes/immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Transgenic ; Receptors, Cell Surface/analysis ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Envelope Proteins/immunology
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  • 65
    Publication Date: 2003-04-12
    Description: The CD8+ cytotoxic T cell response to pathogens is thought to be CD4+ helper T cell independent because infectious agents provide their own inflammatory signals. Mice that lack CD4+ T cells mount a primary CD8 response to Listeria monocytogenes equal to that of wild-type mice and rapidly clear the infection. However, protective memory to a challenge is gradually lost in the former animals. Memory CD8+ T cells from normal mice can respond rapidly, but memory CD8+ T cells that are generated without CD4 help are defective in their ability to respond to secondary encounters with antigen. The results highlight a previously undescribed role for CD4 help in promoting protective CD8 memory development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778341/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778341/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Joseph C -- Bevan, Michael J -- AI 19335/AI/NIAID NIH HHS/ -- R01 AI019335/AI/NIAID NIH HHS/ -- R01 AI019335-19/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):339-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690202" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; CD8-Positive T-Lymphocytes/*immunology/transplantation ; Cytotoxicity, Immunologic ; Genes, MHC Class II ; Immunization ; *Immunologic Memory ; Interferon-gamma/biosynthesis ; Listeria monocytogenes/genetics/immunology ; Listeriosis/*immunology ; Mice ; Mice, Inbred C57BL ; Ovalbumin/biosynthesis/genetics/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Helper-Inducer/*immunology
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  • 66
    Publication Date: 2003-11-01
    Description: Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wen G -- Chang, Qiang -- Lin, Yingxi -- Meissner, Alexander -- West, Anne E -- Griffith, Eric C -- Jaenisch, Rudolf -- Greenberg, Michael E -- HD 18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):885-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/*genetics ; Calcium/*metabolism ; Cell Membrane/physiology ; Cells, Cultured ; *Chromosomal Proteins, Non-Histone ; Cloning, Molecular ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/*metabolism ; Electrophoretic Mobility Shift Assay ; *Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Methyl-CpG-Binding Protein 2 ; Methylation ; Mice ; Mice, Knockout ; Neurons/metabolism/physiology ; Phosphorylation ; Potassium Chloride/pharmacology ; Precipitin Tests ; Promoter Regions, Genetic ; Rats ; *Repressor Proteins ; Rett Syndrome/genetics ; *Transcription, Genetic
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  • 67
    Publication Date: 2003-11-25
    Description: Three distinct classes of drugs: dopaminergic agonists (such as D-amphetamine), serotonergic agonists (such as LSD), and glutamatergic antagonists (such as PCP) all induce psychotomimetic states in experimental animals that closely resemble schizophrenia symptoms in humans. Here we implicate a common signaling pathway in mediating these effects. In this pathway, dopamine- and an adenosine 3',5'-monophosphate (cAMP)-regulated phospho-protein of 32 kilodaltons (DARPP-32) is phosphorylated or dephosphorylated at three sites, in a pattern predicted to cause a synergistic inhibition of protein phosphatase-1 and concomitant regulation of its downstream effector proteins glycogen synthesis kinase-3 (GSK-3), cAMP response element-binding protein (CREB), and c-Fos. In mice with a genetic deletion of DARPP-32 or with point mutations in phosphorylation sites of DARPP-32, the effects of D-amphetamine, LSD, and PCP on two behavioral parameters-sensorimotor gating and repetitive movements-were strongly attenuated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Svenningsson, Per -- Tzavara, Eleni T -- Carruthers, Robert -- Rachleff, Ilan -- Wattler, Sigrid -- Nehls, Michael -- McKinzie, David L -- Fienberg, Allen A -- Nomikos, George G -- Greengard, Paul -- DA10044/DA/NIDA NIH HHS/ -- MH40899/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 21;302(5649):1412-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14631045" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology ; Animals ; Brain/drug effects/*metabolism ; Central Nervous System Agents/*pharmacology ; Corpus Striatum/drug effects/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Dextroamphetamine/pharmacology ; Dopamine/metabolism ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Frontal Lobe/drug effects/metabolism ; Genes, fos ; Glycogen Synthase Kinase 3/metabolism ; Lysergic Acid Diethylamide/pharmacology ; Male ; Mice ; Mice, Knockout ; Motor Activity/drug effects ; Nerve Tissue Proteins/metabolism ; Phencyclidine/pharmacology ; Phosphoprotein Phosphatases/antagonists & inhibitors ; Phosphoproteins/*metabolism ; Phosphorylation ; Protein Phosphatase 1 ; RNA, Messenger/genetics/metabolism ; Receptors, Dopamine D1/genetics/metabolism ; Reflex, Startle/drug effects ; *Signal Transduction ; Synaptic Transmission
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  • 68
    Publication Date: 2003-08-09
    Description: Alternative pre-messenger RNA splicing is an important mechanism for generating protein diversity and may explain in part how mammalian complexity arises from a surprisingly small complement of genes. Here, we describe "digital polony exon profiling,"a single molecule-based technology for studying complex alternative pre-messenger RNA splicing. This technology allows researchers to monitor the combinatorial diversity of exon inclusion in individual transcripts. A minisequencing strategy provides single nucleotide resolution, and the digital nature of the technology allows quantitation of individual splicing variants. Digital polony exon profiling can be used to investigate the physiological and pathological roles of alternately spliced messenger RNAs, as well as the mechanisms by which these messenger RNAs are produced.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Jun -- Shendure, Jay -- Mitra, Robi D -- Church, George M -- 5U54GM62119/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):836-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907803" target="_blank"〉PubMed〈/a〉
    Keywords: Acrylamide ; *Alternative Splicing ; Animals ; Antigens, CD44/genetics ; Brain/metabolism ; Cell Line ; Cell Line, Transformed ; Cyclic AMP Response Element-Binding Protein ; *Exons ; Humans ; Mice ; Microtubule-Associated Proteins/genetics ; Nerve Tissue Proteins/genetics ; Polymerase Chain Reaction/*methods ; Polymorphism, Single Nucleotide ; Protein Isoforms ; RNA Precursors/*genetics/metabolism ; RNA-Binding Proteins ; SMN Complex Proteins
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  • 69
    Publication Date: 2003-01-25
    Description: Disruption of the adaptor protein ELF, a beta-spectrin, leads to disruption of transforming growth factor-beta (TGF-beta) signaling by Smad proteins in mice. Elf-/- mice exhibit a phenotype similar to smad2+/-/smad3+/- mutant mice of midgestational death due to gastrointestinal, liver, neural, and heart defects. We show that TGF-beta triggers phosphorylation and association of ELF with Smad3 and Smad4, followed by nuclear translocation. ELF deficiency results in mislocalization of Smad3 and Smad4 and loss of the TGF-beta-dependent transcriptional response, which could be rescued by overexpression of the COOH-terminal region of ELF. This study reveals an unexpected molecular link between a major dynamic scaffolding protein and a key signaling pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Yi -- Katuri, Varalakshmi -- Dillner, Allan -- Mishra, Bibhuti -- Deng, Chu-Xia -- Mishra, Lopa -- R01 DK56111/DK/NIDDK NIH HHS/ -- R01 DK58637/DK/NIDDK NIH HHS/ -- R03 DK53861/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2003 Jan 24;299(5606):574-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Developmental Biology, Department of Medicine, Georgetown University, Washington, DC 20007, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12543979" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Multiple ; Animals ; Carrier Proteins/metabolism ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Contractile Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Embryonic and Fetal Development ; Filamins ; Gene Targeting ; Genes, fos ; Liver/abnormalities/embryology/*metabolism ; Mice ; Mice, Knockout ; Microfilament Proteins/metabolism ; Microscopy, Confocal ; Mutation ; Phenotype ; Phosphorylation ; Platelet-Derived Growth Factor/pharmacology ; *Signal Transduction ; Smad2 Protein ; Smad3 Protein ; Smad4 Protein ; Spectrin/genetics/*metabolism ; Trans-Activators/metabolism ; Transcriptional Activation ; Transforming Growth Factor beta/*metabolism/pharmacology ; Tumor Cells, Cultured
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  • 70
    Publication Date: 1998-03-21
    Description: The T cell receptor (TCR) inherently has dual specificity. T cells must recognize self-antigens in the thymus during maturation and then discriminate between foreign pathogens in the periphery. A molecular basis for this cross-reactivity is elucidated by the crystal structure of the alloreactive 2C TCR bound to self peptide-major histocompatibility complex (pMHC) antigen H-2Kb-dEV8 refined against anisotropic 3.0 angstrom resolution x-ray data. The interface between peptide and TCR exhibits extremely poor shape complementarity, and the TCR beta chain complementarity-determining region 3 (CDR3) has minimal interaction with the dEV8 peptide. Large conformational changes in three of the TCR CDR loops are induced upon binding, providing a mechanism of structural plasticity to accommodate a variety of different peptide antigens. Extensive TCR interaction with the pMHC alpha helices suggests a generalized orientation that is mediated by the Valpha domain of the TCR and rationalizes how TCRs can effectively "scan" different peptides bound within a large, low-affinity MHC structural framework for those that provide the slight additional kinetic stabilization required for signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, K C -- Degano, M -- Pease, L R -- Huang, M -- Peterson, P A -- Teyton, L -- Wilson, I A -- AI42266/AI/NIAID NIH HHS/ -- AI42267/AI/NIAID NIH HHS/ -- R01 CA58896/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 20;279(5354):1166-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9469799" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallization ; Crystallography, X-Ray ; H-2 Antigens/*chemistry/*immunology/metabolism ; Ligands ; Mice ; Mice, Transgenic ; Models, Molecular ; Mutation ; Oligopeptides/*chemistry/immunology/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/*immunology/metabolism ; Recombinant Proteins
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  • 71
    Publication Date: 1998-12-16
    Description: A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified alpha-DG protein. Soluble alpha-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, alpha-DG is a cellular receptor for both LCMV and LFV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, W -- Henry, M D -- Borrow, P -- Yamada, H -- Elder, J H -- Ravkov, E V -- Nichol, S T -- Compans, R W -- Campbell, K P -- Oldstone, M B -- AG 00080/AG/NIA NIH HHS/ -- AI 09484/AI/NIAID NIH HHS/ -- DK09712/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):2079-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9851928" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arenavirus/metabolism ; Cell Line ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; Dystroglycans ; Lassa virus/*metabolism/physiology ; Lymphocytic choriomeningitis virus/*metabolism/physiology ; Membrane Glycoproteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Receptors, Virus/chemistry/*metabolism ; Recombinant Fusion Proteins/metabolism ; Virus Replication
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  • 72
    Publication Date: 1998-08-07
    Description: The small guanosine triphosphatases (GTPases) Cdc42 and Rac1 regulate E-cadherin-mediated cell-cell adhesion. IQGAP1, a target of Cdc42 and Rac1, was localized with E-cadherin and beta-catenin at sites of cell-cell contact in mouse L fibroblasts expressing E-cadherin (EL cells), and interacted with E-cadherin and beta-catenin both in vivo and in vitro. IQGAP1 induced the dissociation of alpha-catenin from a cadherin-catenin complex in vitro and in vivo. Overexpression of IQGAP1 in EL cells, but not in L cells expressing an E-cadherin-alpha-catenin chimeric protein, resulted in a decrease in E-cadherin-mediated cell-cell adhesive activity. Thus, IQGAP1, acting downstream of Cdc42 and Rac1, appears to regulate cell-cell adhesion through the cadherin-catenin pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuroda, S -- Fukata, M -- Nakagawa, M -- Fujii, K -- Nakamura, T -- Ookubo, T -- Izawa, I -- Nagase, T -- Nomura, N -- Tani, H -- Shoji, I -- Matsuura, Y -- Yonehara, S -- Kaibuchi, K -- New York, N.Y. -- Science. 1998 Aug 7;281(5378):832-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9694656" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cadherins/*metabolism ; *Cell Adhesion ; Cell Cycle Proteins/*metabolism ; Cell Membrane/metabolism ; Cytoskeletal Proteins/metabolism ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/*metabolism ; GTPase-Activating Proteins ; L Cells (Cell Line) ; Mice ; Mutation ; Proteins/*metabolism ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; *Trans-Activators ; alpha Catenin ; beta Catenin ; cdc42 GTP-Binding Protein ; rac GTP-Binding Proteins
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-18
    Description: During T cell activation, the engagement of costimulatory molecules is often crucial to the development of an effective immune response, but the mechanism by which this is achieved is not known. Here, it is shown that beads attached to the surface of a T cell translocate toward the interface shortly after the start of T cell activation. This movement appears to depend on myosin motor proteins and requires the engagement of the major costimulatory receptor pairs, B7-CD28 and ICAM-1-LFA-1. This suggests that the engagement of costimulatory receptors triggers an active accumulation of molecules at the interface of the T cell and the antigen-presenting cell, which then increases the overall amplitude and duration of T cell signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wulfing, C -- Davis, M M -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2266-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigens, CD/*metabolism ; Antigens, CD28/metabolism ; Antigens, CD86 ; Biotinylation ; CHO Cells ; Calcium/metabolism ; Cricetinae ; Cytoskeleton/*physiology ; Intercellular Adhesion Molecule-1/metabolism ; *Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; Microspheres ; Molecular Motor Proteins/physiology ; Myosins/physiology ; Phosphatidylinositol 3-Kinases/metabolism ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism/ultrastructure ; Tumor Cells, Cultured
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sikorski, R -- Peters, R -- New York, N.Y. -- Science. 1998 May 15;280(5366):1101.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9616082" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Library ; Gene Targeting ; *Genetic Techniques ; Genetic Vectors ; Mice ; Mice, Knockout/*genetics ; Mutagenesis, Insertional ; Sequence Analysis, DNA ; *Stem Cells
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cascalho, M -- Wong, J -- Steinberg, C -- Wabl, M -- 1R01 GM37699/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 20;279(5354):1207-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9469811" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenosine Triphosphatases ; Alleles ; Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Base Composition ; Base Sequence ; Cloning, Molecular ; Crosses, Genetic ; *DNA Repair ; *DNA Repair Enzymes ; *DNA-Binding Proteins ; Female ; Gene Rearrangement ; *Genes, Immunoglobulin ; Heterozygote ; Immunoglobulin Heavy Chains/chemistry/genetics ; Immunoglobulin Variable Region/chemistry/*genetics ; Immunoglobulin lambda-Chains/chemistry/genetics ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Data ; *Mutation ; Proteins/*genetics/physiology
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gearhart, J -- New York, N.Y. -- Science. 1998 Nov 6;282(5391):1061-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, MD 21287, USA. gearhart@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9841453" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*cytology ; *Cell Culture Techniques ; Cell Differentiation ; *Cell Line ; Cell Lineage ; *Embryo Research ; Embryo, Mammalian/*cytology ; Federal Government ; Germ Cells/*cytology ; Government Regulation ; Guidelines as Topic ; Humans ; Major Histocompatibility Complex ; Mice ; Research Support as Topic ; Risk Assessment ; Stem Cell Transplantation ; Stem Cells/*cytology ; Transplantation Immunology ; United States
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chess, A -- New York, N.Y. -- Science. 1998 Mar 27;279(5359):2067-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. chess@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9537917" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; DNA Replication ; *Gene Expression Regulation ; Genes, Immunoglobulin ; Interleukin-2/*genetics ; Lymphocyte Activation ; Mice ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction ; Transcription, Genetic
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  • 78
    Publication Date: 1998-02-28
    Description: In the adult mouse, single and compound null mutations in the genes for retinoic acid receptor beta and retinoid X receptors beta and gamma resulted in locomotor defects related to dysfunction of the mesolimbic dopamine signaling pathway. Expression of the D1 and D2 receptors for dopamine was reduced in the ventral striatum of mutant mice, and the response of double null mutant mice to cocaine, which affects dopamine signaling in the mesolimbic system, was blunted. Thus, retinoid receptors are involved in the regulation of brain functions, and retinoic acid signaling defects may contribute to pathologies such as Parkinson's disease and schizophrenia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krezel, W -- Ghyselinck, N -- Samad, T A -- Dupe, V -- Kastner, P -- Borrelli, E -- Chambon, P -- New York, N.Y. -- Science. 1998 Feb 6;279(5352):863-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, Universite Louis Pasteur, College de France, Boite Postale 163, 67404 Illkirch Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9452386" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cocaine/pharmacology ; Corpus Striatum/*metabolism ; Dimerization ; Dopamine/*metabolism ; Locomotion ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Motor Activity/drug effects ; Muscle, Skeletal/physiology ; Parkinson Disease/etiology ; Peripheral Nervous System/physiology ; Receptors, Dopamine D1/genetics/metabolism ; Receptors, Dopamine D2/genetics/metabolism ; Receptors, Retinoic Acid/genetics/*physiology ; Retinoid X Receptors ; Schizophrenia/etiology ; *Signal Transduction ; Transcription Factors/genetics/*physiology
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  • 79
    Publication Date: 1998-12-18
    Description: CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, K M -- Chuang, E -- Griffin, M -- Khattri, R -- Hong, D K -- Zhang, W -- Straus, D -- Samelson, L E -- Thompson, C B -- Bluestone, J A -- P01 AI35294-6/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2263-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ben May Institute for Cancer Research, and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856951" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antigens, CD ; Antigens, Differentiation/*metabolism ; CTLA-4 Antigen ; Cell Line ; Cells, Cultured ; Humans ; *Immunoconjugates ; Intracellular Signaling Peptides and Proteins ; *Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics/metabolism ; Membrane Proteins/*metabolism ; Mice ; Mice, Inbred BALB C ; Models, Immunological ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/genetics/metabolism ; Receptors, Antigen, T-Cell/*metabolism ; Recombinant Fusion Proteins/metabolism ; SH2 Domain-Containing Protein Tyrosine Phosphatases ; *Signal Transduction ; T-Lymphocytes/*immunology ; Transfection ; src Homology Domains
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  • 80
    Publication Date: 1998-04-16
    Description: FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yeh, W C -- de la Pompa, J L -- McCurrach, M E -- Shu, H B -- Elia, A J -- Shahinian, A -- Ng, M -- Wakeham, A -- Khoo, W -- Mitchell, K -- El-Deiry, W S -- Lowe, S W -- Goeddel, D V -- Mak, T W -- CA13106/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1954-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, University of Toronto, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9506948" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Antigens, CD95/genetics/physiology ; *Apoptosis ; Carrier Proteins/genetics/*physiology ; Cell Transformation, Neoplastic ; Cells, Cultured ; Doxorubicin/pharmacology ; *Embryonic and Fetal Development ; Endothelium, Vascular/embryology ; Fas-Associated Death Domain Protein ; Female ; Gene Expression ; Gene Targeting ; Heart/*embryology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Oncogenes ; Receptors, Tumor Necrosis Factor/genetics/physiology ; Signal Transduction ; Tumor Necrosis Factor-alpha/pharmacology
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steel, K P -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1870-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Institute of Hearing Research, Nottingham NG7 2RD, UK. karen@ihr.mrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9537904" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Carrier Proteins/genetics/physiology ; Cell Differentiation ; Chromosome Mapping ; Chromosomes, Human, Pair 5/genetics ; Deafness/*genetics ; Dyneins ; Female ; Gene Targeting ; Genes, Dominant ; Hair Cells, Auditory/physiology ; Hearing Loss, Sensorineural/*genetics ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Male ; Mice ; Myosins/genetics/physiology ; Pedigree ; Sequence Deletion ; Transcription Factor Brn-3C ; Transcription Factors/*genetics/metabolism/physiology
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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-11-30
    Description: Fas ligand (CD95L) inhibits T cell function in immune-privileged organs such as the eye and testis, yet in most tissues CD95L expression induces potent inflammatory responses. With a stably transfected colon carcinoma cell line, CT26-CD95L, the molecular basis for these divergent responses was defined. When injected subcutaneously, rejection of CT26-CD95L was caused by neutrophils activated by CD95L. CT26-CD95L survived in the intraocular space because of the presence of transforming growth factor-beta (TGF-beta), which inhibited neutrophil activation. Providing TGF-beta to subcutaneous sites protected against tumor rejection. Thus, these cytokines together generate a microenvironment that promotes immunologic tolerance, which may aid in the amelioration of allograft rejection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, J J -- Sun, Y -- Nabel, G J -- New York, N.Y. -- Science. 1998 Nov 27;282(5394):1714-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, 1150 West Medical Center Drive, 4520 Medical Science Research Building I, Ann Arbor, MI 48109-0650, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9831564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anterior Chamber ; Apoptosis ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Cytotoxicity, Immunologic ; Fas Ligand Protein ; Female ; Graft Rejection ; Humans ; Immune Tolerance ; Inflammation/*immunology ; Jurkat Cells ; Membrane Glycoproteins/*physiology ; Mice ; Mice, Inbred BALB C ; *Mitogen-Activated Protein Kinases ; Neoplasm Transplantation ; Neoplasms, Experimental/*immunology/pathology ; *Neutrophil Activation ; Neutrophils/immunology ; Transfection ; Transforming Growth Factor beta/pharmacology ; Tumor Cells, Cultured ; p38 Mitogen-Activated Protein Kinases
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  • 83
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chesebro, B -- New York, N.Y. -- Science. 1998 Jan 2;279(5347):42-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Persistent Virus Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA. bchesebro@nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9441410" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/chemistry ; Amyloidosis/metabolism ; Animals ; Cattle ; Creutzfeldt-Jakob Syndrome/epidemiology/*etiology/transmission ; Disease Susceptibility ; Encephalopathy, Bovine Spongiform/epidemiology/*etiology/transmission ; Gene Expression ; Great Britain/epidemiology ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Prion Diseases/*etiology/transmission ; Prions/chemistry/genetics/metabolism/*pathogenicity ; Virus Physiological Phenomena ; Viruses/pathogenicity
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  • 84
    Publication Date: 1998-08-14
    Description: The breast and ovarian cancer susceptibility gene BRCA1 encodes a zinc finger protein of unknown function. Association of the BRCA1 protein with the DNA repair protein Rad51 and changes in the phosphorylation and cellular localization of the protein after exposure to DNA-damaging agents are consistent with a role for BRCA1 in DNA repair. Here, it is shown that mouse embryonic stem cells deficient in BRCA1 are defective in the ability to carry out transcription-coupled repair of oxidative DNA damage, and are hypersensitive to ionizing radiation and hydrogen peroxide. These results suggest that BRCA1 participates, directly or indirectly, in transcription-coupled repair of oxidative DNA damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowen, L C -- Avrutskaya, A V -- Latour, A M -- Koller, B H -- Leadon, S A -- CA40453/CA/NCI NIH HHS/ -- CA70490/CA/NCI NIH HHS/ -- IP50CA58223/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 14;281(5379):1009-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Curriculum in Genetics and Molecular Biology and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9703501" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; BRCA1 Protein/genetics/*physiology ; Cell Line ; DNA Damage ; *DNA Repair ; Hydrogen Peroxide ; Mice ; Oxidation-Reduction ; Stem Cells ; Thymine/analogs & derivatives/immunology/metabolism ; Transcription, Genetic ; Ultraviolet Rays
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  • 85
    Publication Date: 1998-03-21
    Description: Viral infection is sometimes associated with the initiation or exacerbation of autoimmune disease, although the underlying mechanisms remain unclear. One proposed mechanism is that viral determinants that mimic host antigens trigger self-reactive T cell clones to destroy host tissue. An epitope expressed by a coat protein of herpes simplex virus-type 1 (HSV-1) KOS strain has now been shown to be recognized by autoreactive T cells that target corneal antigens in a murine model of autoimmune herpes stromal keratitis. Mutant HSV-1 viruses that lacked this epitope did not induce autoimmune disease. Thus, expression of molecular mimics can influence the development of autoimmune disease after viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Z S -- Granucci, F -- Yeh, L -- Schaffer, P A -- Cantor, H -- AI 37562/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1344-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478893" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Autoantigens/immunology ; Autoimmune Diseases/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Capsid/chemistry/genetics/*immunology ; *Capsid Proteins ; Cornea/*immunology ; Epitopes ; Eye Proteins/immunology ; Herpesvirus 1, Human/*immunology ; Keratitis, Herpetic/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; *Molecular Mimicry ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligopeptides/immunology ; Viral Proteins
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  • 86
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steel, K P -- Brown, S D -- New York, N.Y. -- Science. 1998 May 29;280(5368):1403.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Institute of Hearing Research, University Park, Nottingham NG7 2RD, UK. karen@ihr.mrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9634418" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/physiology ; Animals ; Cilia/physiology ; Deafness/*genetics ; Dyneins ; Extracellular Matrix Proteins/*genetics/physiology ; GPI-Linked Proteins ; Hair Cells, Auditory/physiology/ultrastructure ; Hearing ; Humans ; Membrane Glycoproteins/*genetics/physiology ; Mice ; Mice, Mutant Strains ; Mutation ; Myosin Heavy Chains/genetics/physiology ; Myosins/*genetics/physiology ; Tectorial Membrane/physiology
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  • 87
    Publication Date: 1998-05-09
    Description: Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to Gq class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to Gq.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akhter, S A -- Luttrell, L M -- Rockman, H A -- Iaccarino, G -- Lefkowitz, R J -- Koch, W J -- HL-03041/HL/NHLBI NIH HHS/ -- HL-09436/HL/NHLBI NIH HHS/ -- HL-16037/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Apr 24;280(5363):574-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9554846" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/pharmacology ; Animals ; Atrial Natriuretic Factor/genetics ; COS Cells ; Diglycerides/metabolism ; Enzyme Activation ; GTP-Binding Proteins/antagonists & inhibitors/genetics/*metabolism ; Gene Expression Regulation ; Gene Targeting ; Hypertrophy, Left Ventricular/*metabolism/prevention & control ; Inositol Phosphates/metabolism ; Mice ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 1/metabolism ; Myocardium/*metabolism ; Peptide Fragments/genetics/metabolism ; Phenylephrine/pharmacology ; Receptors, Adrenergic, alpha/*metabolism ; Signal Transduction ; Transfection ; Transgenes ; Ventricular Pressure
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  • 88
    Publication Date: 1998-11-13
    Description: Self tolerance is acquired by the developing immune system. As reported here, particular properties of the neonatal tissue contribute to this process. Neonatal skin, but not adult skin, was accessible for naive CD8 T cells. In mouse bone marrow chimeras generated at different ages, recent thymic emigrants were tolerized to a skin-expressed major histocompatibility complex class I antigen only during a neonatal period but not during adulthood. Blockade of T cell migration neonatally prevented tolerance induction. Thus, T cell trafficking through nonlymphoid tissues in the neonate is crucial for the establishment of self tolerance to sessile, skin-expressed antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alferink, J -- Tafuri, A -- Vestweber, D -- Hallmann, R -- Hammerling, G J -- Arnold, B -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1338-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Antigen Presentation ; Bone Marrow Transplantation ; CD8-Positive T-Lymphocytes/*immunology ; Cell Movement ; Graft Rejection ; H-2 Antigens/*immunology ; Keratinocytes/immunology ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Neoplasms, Experimental/immunology ; Self Tolerance/*immunology ; Skin/*immunology ; Skin Transplantation ; T-Lymphocytes/*immunology ; Thymus Gland/immunology ; Transplantation Chimera
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-11-13
    Description: Human reovirus requires an activated Ras signaling pathway for infection of cultured cells. To investigate whether this property can be exploited for cancer therapy, severe combined immune deficient mice bearing tumors established from v-erbB-transformed murine NIH 3T3 cells or human U87 glioblastoma cells were treated with the virus. A single intratumoral injection of virus resulted in regression of tumors in 65 to 80 percent of the mice. Treatment of immune-competent C3H mice bearing tumors established from ras-transformed C3H-10T1/2 cells also resulted in tumor regression, although a series of injections were required. These results suggest that, with further work, reovirus may have applicability in the treatment of cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coffey, M C -- Strong, J E -- Forsyth, P A -- Lee, P W -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1332-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology Research Group and Department of Microbiology and Infectious Diseases, University of Calgary Health Science Centre, Calgary, Alberta, T2N 4N1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812900" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Antibodies, Viral/immunology ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Line, Transformed ; Genes, erbB ; *Genes, ras ; Humans ; Male ; Mammalian orthoreovirus 3/immunology/*physiology ; Mice ; Mice, Inbred C3H ; Mice, SCID ; Neoplasm Transplantation ; Neoplasms, Experimental/metabolism/pathology/*therapy/virology ; Signal Transduction ; Tumor Cells, Cultured ; Virus Replication ; ras Proteins/*metabolism
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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Mar 6;279(5356):1456.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9508720" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Cells/cytology/*physiology ; Bone Marrow Transplantation ; Cell Differentiation ; Humans ; Mice ; Mice, Transgenic ; Muscle, Skeletal/cytology/pathology/*physiology ; Muscular Dystrophies/pathology/*therapy ; Muscular Dystrophy, Animal/pathology/therapy ; *Regeneration ; Stem Cells/*physiology ; Stromal Cells/physiology
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-07
    Description: In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides-one containing an alphav integrin-binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif-enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arap, W -- Pasqualini, R -- Ruoslahti, E -- CA30199/CA/NCI NIH HHS/ -- CA62042/CA/NCI NIH HHS/ -- CA74238-01/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):377-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430587" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Antineoplastic Agents/*administration & dosage/therapeutic use/toxicity ; Bacteriophages ; Coronary Vessels/drug effects ; Doxorubicin/*administration & dosage/*analogs & ; derivatives/metabolism/therapeutic use/toxicity ; *Drug Carriers ; Heart/drug effects ; Humans ; Integrin alphaV ; Integrins/metabolism ; Liver/blood supply/drug effects ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental/*blood supply/*drug therapy/pathology ; Oligopeptides/*administration & dosage/metabolism/therapeutic use/toxicity ; Peptide Library ; Random Allocation ; Transplantation, Heterologous ; Tumor Cells, Cultured
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  • 92
    Publication Date: 1998-11-13
    Description: The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peschon, J J -- Slack, J L -- Reddy, P -- Stocking, K L -- Sunnarborg, S W -- Lee, D C -- Russell, W E -- Castner, B J -- Johnson, R S -- Fitzner, J N -- Boyce, R W -- Nelson, N -- Kozlosky, C J -- Wolfson, M F -- Rauch, C T -- Cerretti, D P -- Paxton, R J -- March, C J -- Black, R A -- CA43793/CA/NCI NIH HHS/ -- DK53804/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1281-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812885" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Cell Membrane/*metabolism ; Cells, Cultured ; Crosses, Genetic ; *Embryonic and Fetal Development ; L-Selectin/metabolism ; Ligands ; Membrane Proteins/*metabolism ; Metalloendopeptidases/chemistry/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Processing, Post-Translational ; Receptors, Tumor Necrosis Factor/metabolism ; Transforming Growth Factor alpha/metabolism ; Tumor Necrosis Factor-alpha/*metabolism
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  • 93
    Publication Date: 1998-10-17
    Description: The angiopoietins and members of the vascular endothelial growth factor (VEGF) family are the only growth factors thought to be largely specific for vascular endothelial cells. Targeted gene inactivation studies in mice have shown that VEGF is necessary for the early stages of vascular development and that angiopoietin-1 is required for the later stages of vascular remodeling. Here it is shown that transgenic overexpression of angiopoietin-1 in the skin of mice produces larger, more numerous, and more highly branched vessels. These results raise the possibility that angiopoietins can be used, alone or in combination with VEGF, to promote therapeutic angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suri, C -- McClain, J -- Thurston, G -- McDonald, D M -- Zhou, H -- Oldmixon, E H -- Sato, T N -- Yancopoulos, G D -- HL-24136/HL/NHLBI NIH HHS/ -- HL-59157/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1998 Oct 16;282(5388):468-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9774272" target="_blank"〉PubMed〈/a〉
    Keywords: Angiopoietin-1 ; Animals ; Capillaries/anatomy & histology/ultrastructure ; Endothelial Growth Factors/genetics/physiology ; Endothelium, Vascular/ultrastructure ; Gene Expression ; Keratinocytes/metabolism ; Lymphokines/genetics/physiology ; Membrane Glycoproteins/genetics/*physiology ; Mice ; Mice, Transgenic ; *Neovascularization, Physiologic ; Skin/*blood supply/metabolism ; Transgenes ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Venules/anatomy & histology/ultrastructure
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, C -- Erbisch, F -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):33-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9917260" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biotechnology ; Mice ; Mice, Transgenic ; *Patents as Topic ; Plants, Genetically Modified/*genetics ; United States
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Apr 30;284(5415):723, 725.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10336390" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Breast Neoplasms/*genetics/pathology ; *Disease Models, Animal ; Female ; *Genes, BRCA1 ; Genes, p53 ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Animal/*genetics/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Mutation
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  • 96
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, I -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1826-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610569" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/cytology ; Cell Differentiation ; Cell Survival ; Embryo, Mammalian ; Mice ; Neurons/cytology ; Oligodendroglia/cytology ; Rats ; Spinal Cord/cytology/*physiology ; Spinal Cord Injuries/*therapy ; *Stem Cell Transplantation ; Stem Cells/cytology
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hardin, P E -- Glossop, N R -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2460-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Houston, Houston, TX 77204, USA. phardin@uh.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636810" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Biological Clocks/*physiology ; CLOCK Proteins ; Cell Cycle Proteins ; Circadian Rhythm/*physiology ; Cryptochromes ; Darkness ; Drosophila ; *Drosophila Proteins ; *Eye Proteins ; Feedback ; Flavoproteins/genetics/*physiology ; Gene Expression Regulation ; Light ; Mice ; Mice, Knockout ; Nuclear Proteins/*genetics/metabolism ; Period Circadian Proteins ; *Photoreceptor Cells, Invertebrate ; Promoter Regions, Genetic ; Receptors, G-Protein-Coupled ; Repressor Proteins/genetics/physiology ; Suprachiasmatic Nucleus/metabolism ; Trans-Activators/physiology ; Transcription Factors/physiology ; *Transcription, Genetic
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  • 98
    Publication Date: 1999-10-03
    Description: Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, C L -- Ouellette, A J -- Satchell, D P -- Ayabe, T -- Lopez-Boado, Y S -- Stratman, J L -- Hultgren, S J -- Matrisian, L M -- Parks, W C -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10506557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalysis ; Cytoplasmic Granules/enzymology ; Escherichia coli/growth & development ; Escherichia coli Infections/immunology/microbiology ; Female ; Humans ; *Immunity, Innate ; *Immunity, Mucosal ; Intestinal Mucosa/enzymology/immunology/microbiology ; Intestine, Small/enzymology/*immunology/microbiology ; Male ; Matrix Metalloproteinase 7 ; Metalloendopeptidases/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Paneth Cells/enzymology ; Protein Precursors/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Salmonella typhimurium/growth & development/pathogenicity ; Tissue Extracts/pharmacology
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, I A -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1867-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. wilson@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610577" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/*chemistry/immunology/metabolism ; Binding Sites ; CD4-Positive T-Lymphocytes/immunology/metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Crystallography, X-Ray ; Histocompatibility Antigens Class I/chemistry/immunology/metabolism ; Histocompatibility Antigens Class II/*chemistry/immunology/metabolism ; Mice ; Models, Molecular ; Peptides/chemistry/immunology/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/immunology/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1999-12-11
    Description: Natural antibodies are often dismissed from immunological analysis as "background," but they may play an important role in conferring immunity against infections. In antibody-free mice infected with various viruses or with Listeria monocytogenes, viral or bacterial titers in peripheral organs, including the kidney and brain, were 10 to 100 times greater than in antibody-competent mice (and enhanced their susceptibility to some infections), and titers in secondary lymphoid organs were 10 to 100 times lower than in antibody-competent mice. Thus, natural antibodies play a crucial role by preventing pathogen dissemination to vital organs and by improving immunogenicity through enhanced antigen-trapping in secondary lymphoid organs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ochsenbein, A F -- Fehr, T -- Lutz, C -- Suter, M -- Brombacher, F -- Hengartner, H -- Zinkernagel, R M -- New York, N.Y. -- Science. 1999 Dec 10;286(5447):2156-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10591647" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bacterial/blood/immunology ; Antibodies, Viral/blood/immunology ; Bacterial Infections/*immunology/microbiology ; Germ-Free Life ; *Immunity, Innate ; Immunoglobulin M/blood/*immunology ; Kidney/microbiology/virology ; Listeria monocytogenes/immunology/physiology ; Listeriosis/immunology ; Lymphocytic choriomeningitis virus/immunology/physiology ; Lymphoid Tissue/immunology/microbiology/virology ; Mice ; Mice, Inbred C57BL ; Neutralization Tests ; Rhabdoviridae Infections/immunology/virology ; Specific Pathogen-Free Organisms ; Spleen/microbiology/virology ; Vaccinia virus/immunology/physiology ; Vesicular stomatitis Indiana virus/immunology/physiology ; Virus Diseases/*immunology/virology ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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