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PubMed1991

Divergent selection for growth in Japanese quail under split and complete nutritional environments. 4. Genetic and correlated responses from generations 12 to 20.

Divergent selection during Generations 12 to 20 for high (H) and low (L) 4-wk BW under split-(SD) and complete-(CD) diet environments resulted in continued progress in both upward and downward directions. Following 20 generations of selection, there were 4.8- and 3.6-fold differences between BW of H and L lines in the SD and CD environments, respectively. Regression coefficients of mean 4-wk BW on generation of 1.88 and 1.58 g in the H lines and -1.50 and -1.37 g in the L lines indicated symmetrical selection responses. Realized heritabilities for 4-wk BW ranged from .2 to .4; selection differentials were significantly (P less than .01) larger in the H lines than in the L lines. Directional changes in 2-wk and adult BW and in egg weight across generations were similar to that of the selection trait (4-wk BW). Selection resulted in decreased hatchability and egg production and an increase in the age of sexual maturity. However, these changes were smaller than corresponding changes observed in earlier generations (0 to 11). Egg size of lines selected in the SD environment continued to be larger than egg size of corresponding lines in the CD environment. Considerable genetic variation for BW remains under both SD and CD environments following 20 generations of divergent selection. Smaller gains resulting from lower heritabilities agree with theoretical expectations of decreasing responses accompanying continuous selection.

Animals↗
PubMed2004

WordGen: a tool for word selection and nonword generation in Dutch, English, German, and French.

WordGen is an easy-to-use program that uses the CELEX and Lexique lexical databases for word selection and nonword generation in Dutch, English, German, and French. Items can be generated in these four languages, specifying any combination of seven linguistic constraints: number of letters, neighborhood size, frequency, summated position-nonspecific bigram frequency, minimum position-nonspecific bigram f requency, position-specific frequency of the initial and final bigram, and orthographic relatedness. The program also has a module to calculate the respective values of these variables for items that have already been constructed, either with the program or taken from earlier studies. Stimulus queries can be entered through WordGen's graphical user interface or by means of batch files. WordGen is especially useful for (1) Dutch and German item generation, because no such stimulus-selection tool exists for these languages, (2) the generation of nonwords for all four languages, because our program has some important advantages over previous nonword generation approaches, and (3) psycholinguistic experiments on bilingualism, because the possibility of using the same tool for different languages increases the cross-linguistic comparability of the generated item lists. WordGen is free and available at http://expsy.ugent.be/wordgen.htm.

Choice Behavior↗
PubMed2004

Processing strategies and the generation effect: implications for making a better reader.

When presented with items that must be generated versus read at encoding, individuals typically remember better those items that they generated versus those that they only read. We examined whether--given the opportunity to experience such differential memorial consequences of generating versus reading--participants might change how they processed future to-be-read information. In a first set of two experiments, participants were able to profit from such an experience to the extent that a generation advantage was eliminated on subsequent memory tests of generated and read items. Two additional experiments demonstrated the critical nature of this experience in leading to improved processing of future to-be-read information and elimination of a generation advantage. We believe that these results relate to the characterization of the learner emerging from recent metacognitive research and have possible implications for how learners might be induced to process information more effectively.

Cognition↗
PubMed1999

A beautiful day in the neighborhood: what factors determine the generation effect for simple multiplication problems?

In four experiments, we examined the generation effect for the free recall of simple multiplication answers. Large-product-size problems showed a consistent generation-effect advantage over small-product-size problems, except when each answer was generated twice, via two different sets of operands (Experiment 2). Also, measures of problem-solution time and strategy use accounted for the large-product-size advantage. Across experiments, however, small-product-size problems (but not large-product-size problems) showed considerable variation in the size of their generation effect. We discovered that solving small-product-size problems via direct memory retrieval increased the episodic recall probability of other problems that were near neighbors to the generated answer, and we attribute this result to a spreading activation mechanism in semantic memory. A measure of neighbor activations, combined with RT to solve each problem, accounted for 51% of the observed generation-effect variance.

Adolescent↗
PubMed1993

The effects of generation on item and order retention in immediate and delayed recall.

Recent research has shown that generating words from fragments, relative to simply reading them, inhibits processing of order information. Nairne, Riegler, and Serra (1991) showed that this reduction in processing of order information leads to deficits in recall performance. In three experiments, we generally replicate Nairne et al.'s results and demonstrate that the deficit in recall for the generated items is dependent on the easy distractor task and the relatively short (30-sec) retention interval they used. When a difficult distractor task was used, generating produced a deficit in amount of order information processed, but actually facilitated recall when recall was delayed 80 sec. The results are consistent with the hypothesis that generating words inhibits order processing, but they do not support the contention that the reduction in order processing is responsible for the deficit in recall that is sometimes observed for the generated items. The importance of the item-order distinction in explaining the generation effect, as well as the role of the item-order distinction in the long-term-memory arena, is questioned.

Adolescent↗
PubMed1993

Design controversies and the generation effect: support for an item-order hypothesis.

We performed three experiments to investigate an earlier finding of Nairne, Riegler, and Serra (1991) that item generation disrupts the long-term retention of serial order. Experiment 1 demonstrated a clear advantage of reading over generating on a reconstruction test when reading and generating occurred in pure, but not mixed, lists. Experiment 2 showed that the standard generate advantage is seen in free recall of mixed, but not pure, lists, even when recall is immediately followed by reconstruction of serial order of the same items. Experiment 3 replicated Experiment 1, but with the use of an incidental learning procedure. The results of all three experiments are consistent with the claim that generation has dissociative effects on item and order memory; moreover, these dissociative effects help to explain design controversies in the generation effect literature.

Adult↗
PubMed1998

The time-course of the generation effect.

The generation effect, in which items generated by following some rule are remembered better than stimuli that are simply read, has been studied intensely over the past two decades. To date, however, researchers have largely ignored the temporal aspects of this effect. In the present research, we used a variable onset time for the presentation of the to-be-remembered material, thus providing the ability to determine at what point during processing the generation effect originates. The results indicate that some benefit from generation attempts occurs even when subjects have only a few hundred milliseconds in which to process the stimulus, but that more of the benefit occurs later. This finding suggests that the generation effect results from continuous or multiple discrete stages of information accrual or strengthening of memory traces over time, rather than from a single discrete increment upon final generation.

Analysis of Variance↗
PubMed2000

Either B7 costimulation or IL-2 can elicit generation of primary alloreactive CTL.

B7-1 and B7-2 are important costimulatory molecules in the activation of T cell immunity. We have used mice made genetically deficient in either or both B7 molecules to determine the role of B7 molecules in activation of primary alloreactive CTL. The absence of either B7-1 or B7-2 did not alter generation of CTL from unfractionated lymphocytes, but the absence of B7-2 greatly decreased CTL generation from purified CD8+ responder cells. However, if B7-1 was induced on the stimulating cells then CTL generation was restored to wild-type levels. Absence of both B7-1 and B7-2 from MLR using whole splenocytes resulted in a profound reduction in generation of CTL. This could completely be reversed by the addition of IL-2. B7 molecules could directly costimulate CD8+ cells, as purified CD8+ cells developed into mature CTL when stimulated with wild-type APC, but not with B7-deficient APC. Again, IL-2 could drive CTL generation from purified CD8+ cells, even in the absence of B7 molecules. Taken together, these results demonstrate an important role for B7 costimulation in CTL generation.

Animals↗
PubMed2002

Eotaxin-2 generation is differentially regulated by lipopolysaccharide and IL-4 in monocytes and macrophages.

The eotaxins are a family of CC chemokines that coordinate the recruitment of inflammatory cells, in particular eosinophils, to sites of allergic inflammation. The cDNA for eotaxin-2 (CC chemokine ligand 24) was originally isolated from an activated monocyte library. In this study, we show for the first time that peripheral blood monocytes generate bioactive eotaxin-2 protein constitutively. Eotaxin-2 production was significantly up-regulated when monocytes were stimulated with the proinflammatory cytokine IL-1beta and the microbial stimuli, LPS and zymosan. In contrast, the Th2 cytokines, IL-4 and IL-13, and the proinflammatory cytokine, TNF-alpha, acting alone or in combination, did not enhance the generation of eotaxin-2 by monocytes. Indeed, IL-4 suppressed the generation of eotaxin-2 by LPS-stimulated monocytes. Although other chemokines, including macrophage-inflammatory protein-1alpha, monocyte chemoattractant protein-1, macrophage-derived chemokine, and IL-8 were generated by monocytes, eotaxin-1 (CC chemokine ligand 11) could not be detected in the supernatants of monocytes cultured in the presence or absence of any of the stimuli used in the above experiments. Furthermore, human dermal fibroblasts that produce eotaxin-1 did not generate eotaxin-2 under basal conditions or when stimulated with specific factors, including IL-4, IL-13, TNF-alpha, and LPS. When monocytes were differentiated into macrophages, their constitutive generation of eotaxin-2 was suppressed. Moreover, IL-4, but not LPS, up-regulated the production of eotaxin-2 by macrophages. Taken as a whole, these results support a role for macrophage-derived eotaxin-2 in adaptive immunity, with a Th2 bias. In contrast, a role for monocyte-derived eotaxin-2 is implicated in innate immunity.

Cells, Cultured↗
PubMed2004

CCL17 and IL-10 as effectors that enable alternatively activated macrophages to inhibit the generation of classically activated macrophages.

Classically activated macrophages (CAMphi) have been described as a major effector cell on the host's innate immunities. However, CAMphi are not generated in immunocompromised hosts whose alternatively activated macrophages (AAMphi) predominate. In this study, the mechanism by which AAMphi suppress the ability of resident macrophages (RMphi) to generate CAMphi was investigated. AAMphi were isolated from peritoneal exudates of mice 2 days after third-degree thermal injuries affecting 15% total body surface area. CAMphi were generated from RMphi (peritoneal Mphi from normal mice) through stimulation with CpG DNA, a typical CAMphi inducer. RMphi did not polarize to CAMphi when they were cultured with AAMphi in a dual-chamber Transwell even when supplemented with CpG DNA. In addition, RMphi stimulated with CpG DNA did not convert to CAMphi when they were cultured with the culture fluids of AAMphi (AAMphi Culture-Sup). AAMphi Culture-Sup contained IL-6, IL-10, CCL17, PGE(2), and TGF-beta. Among these, CCL17 and IL-10 inhibited CAMphi generation. The ability of AAMphi Culture-Sup to inhibit CAMphi generation was eliminated when the Culture-Sup was treated with a mixture of mAbs directed against CCL17 and IL-10. These results indicate that CCL17 and IL-10 released from AAMphi inhibit CAMphi generation from RMphi stimulated with CpG DNA.

Animals↗
PubMed2005

Generation of high-affinity antibody against T cell-dependent antigen in the Ganp gene-transgenic mouse.

Generation of high-affinity Ab is impaired in mice lacking germinal center-associated DNA primase (GANP) in B cells. In this study, we examined the effect of its overexpression in ganp transgenic C57BL/6 mice (Ganp(Tg)). Ganp(Tg) displayed normal phenotype in B cell development, serum Ig levels, and responses against T cell-independent Ag; however, it generated the Ab with much higher affinity against nitrophenyl-chicken gammaglobulin in comparison with C57BL/6. To further examine the affinity increase, we established hybridomas producing high-affinity mAbs and compared their affinities using BIAcore. C57BL/6 generated high-affinity anti-nitrophenyl mAbs (K(D) approximately 2.50 x 10(-7) M) of IgG1/lambda1 and contained the V(H)186.2 region with W33L mutation. Ganp(Tg) generated much higher affinity (K(D) > 1.57 x 10(-9) M) by usage of V(H)186.2 as well as noncanonical V(H)7183 regions. Ganp(Tg) also generated exceptionally high-affinity anti-HIV-1 (V3 peptide) mAbs (K(D) > 9.90 x 10(-11) M) with neutralizing activity. These results demonstrated that GANP is involved in V region alteration generating high-affinity Ab.

Amino Acid Sequence↗
PubMed1993

[Effect of information generation on incidental memory of words].

The present study was carried out to investigate the effect of information generation on incidental memory of words. Subjects in the subject-generated group were asked to generate a converging associate of three targets in each triplet. Subjects in the experimenter-provided group were asked to rate the relation between targets and a paired-presented word on 5-point scale. Each subject in both groups were given an unexpected free recall test. Recall performance for targets in each unrelated triplet in the subject-generated group was higher than in the experimenter-provided one. Conditional probability of recalling targets given relational information was an index of effectiveness of within-item elaboration. This index was higher in the subject-generated group. These results were interpreted as showing that the effect of information generation was caused by the effectiveness of within-item elaboration.

Adult↗
PubMed1999

Protein kinase C-activated oxidant generation in endothelial cells signals intercellular adhesion molecule-1 gene transcription.

We tested the hypothesis that activation of protein kinase C (PKC) and generation of oxidants are critical sequential signals mediating tumor necrosis factor (TNF)-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) and transcription of the intercellular adhesion molecule (ICAM)-1 gene. Stimulation of human pulmonary artery endothelial (HPAE) cells with TNF-alpha (100 U/ml) induced the activation of PKC and, subsequently, generation of oxidants. Pretreatment with calphostin C, a specific PKC inhibitor, prevented oxidant generation after TNF-alpha stimulation, indicating that PKC activation mediated the production of oxidants in HPAE cells. In contrast, pretreatment of HPAE cells with N-acetylcysteine, an antioxidant and a precursor of glutathione, failed to prevent PKC activation, indicating that PKC activation was not secondary to the oxidant production. These findings suggest that oxidant generation in endothelial cells occurs downstream of PKC activation. However, both PKC activation and oxidant generation were necessary for ICAM-1 mRNA expression because the pretreatment of HPAE cells with either calphostin C or N-acetylcysteine inhibited the TNF-alpha-induced activation of NF-kappaB and prevented the activation of ICAM-1 promoter. Prolonged exposure of HPAE cells to the phorbol ester, phorbol-12-myristate-13-acetate, which is known to deplete all except atypical PKC isozymes, failed to prevent TNF-alpha-induced ICAM-1 mRNA expression. We conclude that TNF-alpha-induced oxidant generation secondary to the activation of a phorbol ester-insensitive PKC isozyme signals the activation NF-kappaB and ICAM-1 gene transcription.

Cells, Cultured↗
PubMed1999

Phospholipid-bound tissue factor modulates both thrombin generation and APC-mediated factor Va inactivation.

Hemostasis is initiated by tissue factor (TF) exposed on cellular phospholipid (PL) membranes, leading to thrombin generation. The binding of thrombin to thrombomodulin (TM), activates the protein C pathway, resulting in the inactivation of factors Va and VIIIa by activated protein C (APC) and a negative feedback effect on thrombin generation. A new assay system was developed for simultaneous measurement of thrombin and APC generation in defibrinated plasma induced by large unilamellar PL vesicles complexed with full-length recombinant TF (TF:PL). TF:PL preparations with a low TF concentration induced an initial rate of thrombin generation below 100 nM/min, and resulted in less thrombin formation in the presence of TM than in its absence. In contrast, TF:PL preparations with a high concentration of TF induced a higher rate of thrombin generation, and APC-mediated feedback inhibition did not occur, despite maximal APC generation. We used the same TF:PL surfaces to study factor Va inactivation by APC in a non-plasma reaction system, and found an inverse correlation between TF surface density and the rate of factor Va inactivation. This observation suggests a previously unrecognized hemostatic effect of TF, namely a non-enzymatic surface density-based inhibition of the anticoagulant effect of APC. In this model, high concentrations and surface density of TF exert complementary effects by promoting the regular procoagulant cascade and by inhibiting the protein C pathway, thereby maximizing hemostasis after vascular injury.

Animals↗
PubMedDate not supplied

Are you ready for generation X?

Generational analysis considers the differences in world view and attitude between various generations of Americans and uses this information to develop insight and business strategies. The much discussed generation gap between the Baby Boomers and their elders during the 1960s and 1970s is equaled or exceeded by the differences between Generations X and Y and the Boomers. Generation X physicians will be coming into practice over the next two decades. Successful medical leaders must understand Gen-Xers to create clinical environments that meet their unique needs and concerns. This article describes some of the philosophical and attitudinal differences between the generations and what these differences may mean to the future of medicine and health care organizations.

Attitude of Health Personnel↗
PubMed2000

Generation of transmembrane electrical potential during NADH oxidation via the external pathway and the fatty acid uncoupling effect after transient opening of the Ca2+-dependent cyclosporin A-sensitive pore in liver mitochondria.

The effects of transient pore opening on generation of the transmembrane gradient of electrical potential across the inner mitochondrial membrane (DeltaPsi) induced by NADH oxidation through the external pathway as well as on the uncoupling effect of fatty acids were studied. The pore opening was monitored by changes in the DeltaPsi value. The cycle of pore opening/closing was found to have only an insignificant effect on the sensitivity of DeltaPsi to fatty acid uncoupling. Once this cycle is over, NADH oxidation in the presence of exogenous cytochrome c results in generation of DeltaPsi. In the absence of cytochrome c, the generation of DeltaPsi induced by oxidation of exogenous NADH is observed if the incubation medium pH has been decreased from 7.4 to 7.0. The generation of DeltaPsi was inhibited by cyclosporin A. In isotonic salt medium containing 125 mM KCl, the maximum level of DeltaPsi generated by exogenous NADH after the cycle of pore opening/closing was significantly lower than the maximum level of DeltaPsi generated in hypotonic incubation medium. The data obtained in this work suggest that the cycle of pore opening/closing has little if any effect on the energy coupling in liver mitochondria, whereas the external pathway of NADH oxidation activated by this cycle may support the energy-dependent functions of liver mitochondria.

Animals↗
PubMed2000

Anti-beta2-glycoprotein I autoantibodies, in vitro thrombin generation, and the antiphospholipid syndrome.

OBJECTIVE: Thrombin plays a pivotal role in the regulation of hemostasis. We examined the effect of antiphospholipid (aPL) antibodies, in particular those with specificity for beta2-glycoprotein I (beta2-GPI), on in vitro thrombin generation, and examined the association with clinical manifestations of the antiphospholipid syndrome (APS). METHODS: We studied plasma samples from 59 patients with aPL antibodies determined by the presence of either elevated anticardiolipin (aCL) antibodies or lupus anticoagulant (LAC). Direct antibody binding of IgG, IgM, and IgA to beta2-GPI and prothrombin (PT) was determined by ELISA. Affinity purification of total IgG and IgG anti-B2-GPI antibodies was performed using staphylococcal protein A and phospholipid liposomes. A chromogenic assay was used to determine the effect of plasma samples and purified autoantibodies on in vitro thrombin generation. RESULTS: Thirty-three of 59 (56%) plasma samples inhibited in vitro generation of thrombin and 7/59 (12%) accelerated thrombin formation. There was a strong negative correlation between thrombin generation and IgG aCL (r = -0.72, p < 0.001) and IgG anti-beta2-GPI (r = -0.71, p < 0.001) antibody levels, and a weaker correlation with LAC (r = -0.46, p = 0.001). This association was not found with anti-PT antibodies and could not be attributed to concurrent therapy with warfarin. Additional experiments with affinity purified IgG antibodies indicated a dose dependent inhibition of thrombin generation, which was restricted to anti-beta2-GPI antibodies. Patients with a history of core clinical manifestations of the APS [venous and arterial thrombosis, recurrent (> or = 2) fetal loss] had significantly greater inhibition of in vitro thrombin generation (mean +/- SEM Z score: -3.38 +/- 0.51 vs -1.42 +/- 0.56; p = 0.01) and higher levels of IgG aCL (mean +/- SEM Z score: 8.39 +/- 1.12 vs 5.39 +/- 0.88; p = 0.04) and IgG anti-beta2-GPI antibodies (mean +/- SEM Z score: 4.49 +/- 0.69 vs 2.26 +/- 0.54; p = 0.01). Odds ratios for these variables and clinical manifestations of the APS were 5.43, 4.17, and 3.28, respectively. CONCLUSION: aPL antibodies may accelerate or inhibit the rate of in vitro thrombin formation. The predominant effect is inhibition that is restricted to IgG anti-beta2-GPI antibodies and it is strongly associated with clinical manifestations of the APS.

Antiphospholipid Syndrome↗
PubMed2000

Dietary proteins on reproductive performance in three consecutive generations of rats.

The cumulative effects of the long-term consumption of the Regional Basic Diet (RBD) of Northeast Brazil on gestational and lactational performances were assessed in three consecutive generations of Sprague Dawley rats (n = 1,334). The animals were distributed into three groups: RBD (8% predominantly vegetable-based proteins), Control (8% casein) and Standard (22% casein). Primiparous fertilized rats aged 120 days old and their offsprings made up generation 1. Consecutive generations were obtained by mating products from previous generations. Statistical differences between groups and generations were analysed by the method of Kruskal-Wallis. In comparison with their respective controls, data for RBD-fed groups were as follows: decreased conception rates, gradual declines in gestational body weight gains and reduction in the mean number of youngs per litter; the weight loss of lactating rats aggravated in consecutive generations; suckling rats had lower values for birthweight and weight gain, higher values for death rates (including soon after weaning) and severe immaturity at weaning (21 days). This dietary experimental model proved to be valid in terms of providing information for further studies about the relationship between quality and quantity of dietary proteins in order to allow decisions on supplementary feeding programmes for people now most in need.

Animals↗