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Additive Effects (additive + effects)
Selected AbstractsA Coherent Mechanistic Rationale for Additive Effects and Autoinductive Behaviour in Proline-Mediated ReactionsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2009Natalia Zotova Abstract Differences in the kinetic behaviour of aldol reactions compared to aminoxylation and amination reactions are rationalized by consideration of the rate-determining step in each case. Both autoinductive behaviour and the rate-enhancing effect of additives are attributed to an effect on the enamine formation step. [source] Pressureless Sintering of Zirconium Diboride: Particle Size and Additive EffectsJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 5 2008William G. Fahrenholtz Zirconium diboride (ZrB2) was densified by pressureless sintering using <4-wt% boron carbide and/or carbon as sintering aids. As-received ZrB2 with an average particle size of ,2 ,m could be sintered to ,100% density at 1900°C using a combination of boron carbide and carbon to react with and remove the surface oxide impurities. Even though particle size reduction increased the oxygen content of the powders from ,0.9 wt% for the as-received powder to ,2.0 wt%, the reduction in particle size enhanced the sinterability of the powder. Attrition-milled ZrB2 with an average particle size of <0.5 ,m was sintered to nearly full density at 1850°C using either boron carbide or a combination of boride carbide and carbon. Regardless of the starting particle size, densification of ZrB2 was not possible without the removal of oxygen-based impurities on the particle surfaces by a chemical reaction. [source] Oscillatory activity in parietal and dorsolateral prefrontal cortex during retention in visual short-term memory: Additive effects of spatial attention and memory loadHUMAN BRAIN MAPPING, Issue 10 2009Stéphan Grimault Abstract We used whole-head magnetoencephalography to study the representation of objects in visual short-term memory (VSTM) in the human brain. Subjects remembered the location and color of either two or four colored disks that were encoded from the left or right visual field (equal number of distractors in the other visual hemifield). The data were analyzed using time-frequency methods, which enabled us to discover a strong oscillatory activity in the 8,15 Hz band during the retention interval. The study of the alpha power variation revealed two types of responses, in different brain regions. The first was a decrease in alpha power in parietal cortex, contralateral to the stimuli, with no load effect. The second was an increase of alpha power in parietal and lateral prefrontal cortex, as memory load increased, but without interaction with the hemifield of the encoded stimuli. The absence of interaction between side of encoded stimuli and memory load suggests that these effects reflect distinct underlying mechanisms. A novel method to localize the neural generators of load-related oscillatory activity was devised, using cortically-constrained distributed source-localization methods. Some activations were found in the inferior intraparietal sulcus (IPS) and intraoccipital sulcus (IOS). Importantly, strong oscillatory activity was also found in dorsolateral prefrontal cortex (DLPFC). Alpha oscillatory activity in DLPFC was synchronized with the activity in parietal regions, suggesting that VSTM functions in the human brain may be implemented via a network that includes bilateral DLPFC and bilateral IOS/IPS as key nodes. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Evaluation of Garam Masala Spices and Phosphates as Antioxidants in Cooked Ground BeefJOURNAL OF FOOD SCIENCE, Issue 5 2006Mihir N. Vasavada ABSTRACT:, This study determined antioxidant effects and sensory attributes of individual ingredients (black pepper, caraway, cardamom, chili powder, cinnamon, cloves, coriander, cumin, fennel, ginger, nutmeg, salt, star anise) of an Indian spice blend (garam masala) in cooked ground beef. Thiobarbituric acid (TBA) values were measured as an indicator of rancidity for cooked samples on 1-, 8-, or 15-d refrigerated storage. Cooked samples were evaluated by a trained panel (n= 13) for the intensity of rancid odor/flavor, beef flavor, and spice flavor and correlated with TBA values of same day samples. We also investigated possible additive effects between spice antioxidants and iron binding (type II) antioxidants on lipid oxidation by measuring TBA values. All spices had antioxidant effects on cooked ground beef, compared to controls. Among spices, cloves were the most effective in controlling lipid oxidation, with TBA values of 0.75, after 15-d refrigerated storage. All spices at their recommended levels lowered rancid odor and flavor in cooked ground beef, compared to controls. As expected, most spices also imparted distinctive flavors to cooked ground beef. There was a positive correlation (0.77) between TBA values on 15-d refrigerated storage and rancid odor/flavor. Type II antioxidants (iron-binding phosphate compounds) were more effective than individual type I antioxidants (spices and butylated hydroxytoluene; BHT) for maintenance of low TBA values in cooked ground beef during storage. Additive effects were observed with rosemary + milk mineral or sodium tripolyphosphate (STP) compared to rosemary alone. [source] Irritants in combination with a synergistic or additive effect on the skin response: an overview of tandem irritation studiesCONTACT DERMATITIS, Issue 6 2006Francisca Kartono Sodium lauryl sulfate (SLS) has often been chosen as a model for irritant contact dermatitis (ICD) to study the effect of irritants in combination (1,14). Recently ,tandem', or sequential, exposures with SLS have been performed to study the mechanism of skin barrier impairment in ICD (1,6, 15). The assessment of reactions have been documented with visual scoring, transepidermal water loss (TEWL), skin colour reflectance measurements, skin blood flow; among which TEWL has been noted as the most sensitive value (16). The matched control groups were treated with either a single exposure to a single irritant or in tandem with the same irritant repeatedly. Synergistic and additive effects have been reported for various tandem pairs of irritants, however, the mechanism for both remains unclear. The results of tandem irritation studies were evaluated to define and investigate the responses produced and deduce a possible mechanism of action. Clinical ramifications, albeit complex, are discussed. [source] Transcranial magnetic stimulation in child psychiatry: disturbed motor system excitability in hypermotoric syndromesDEVELOPMENTAL SCIENCE, Issue 3 2002Gunther H. Moll Normal development and dysfunctions of motor system excitability can be investigated in vivo by means of single- and paired-pulse transcranial magnetic stimulation (TMS). While different TMS-parameters show different developmental time courses between 8 and 16 years of age, distinct dysfunctional patterns of motor system excitability can be demonstrated in child psychiatric disorders with hypermotoric behavior: in tic disorder, a shortened cortical silent period can be stated providing evidence for deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. In attention deficit hyperactivity disorder (ADHD), a decreased intracortical inhibition indicates deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In children with comorbid ADHD and tic disorder, the findings of a reduced intracortical inhibition as well as a shortened cortical silent period provide evidence for additive effects at the level of motor system excitability. Thus, TMS allows us to obtain substantial insight into both the normal development and the neurobiological basis of hypermotoric syndromes in child psychiatry. [source] Xanthine-analog, KMUP-2, enhances cyclic GMP and K+ channel activities in rabbit aorta and corpus cavernosum with associated penile erectionDRUG DEVELOPMENT RESEARCH, Issue 3 2002Rong-Jyh Lin Abstract The pharmacological properties of KMUP-2 were examined in isolated rabbit aorta and corpus cavernosum smooth muscle (CCSM). KMUP-2 caused relaxations that were attenuated by removed endothelium, high K+, and pretreatment with the soluble guanylate cyclase (sGC) inhibitors methylene blue (10 ,M) and ODQ (1 ,M), a NOS inhibitor, L-NAME (100 ,M), a K+ channel blocker TEA (10 mM), a KATP channel blocker glibenclamide (1 ,M), a voltage-dependent K+ channel blocker 4-AP (100 ,M), and the Ca2+ -dependent K+ channel blockers apamin (1 ,M) and charybdotoxin (ChTX, 0.1 ,M). The relaxant responses of KMUP-2 (0.01, 0.05, 0.1 ,M) together with a PDE inhibitor, IBMX (0.5 ,M), had additive effects on rabbit aorta and CCSM. Additionally, KMUP-2 (100 ,M) also affected cGMP metabolism, due to its inhibiting activity on PDE in human platelets. KMUP-2 (0.1,100 ,M) further induced an increase of intracellular cGMP levels in the primary cultured rabbit aortic and CCSM cells. These increases in cGMP content were abolished in the presence of methylene blue (100 ,M) and ODQ (10 ,M). Obviously, the relaxant effects of KMUP-2 on rabbit isolated tissues are more sensitive in CCSM than in aorta. Moreover, KMUP-2 also stimulated NO/sGC/cGMP pathway and subsequent elevation of cGMP by blockade of PDE and enhanced opening of K+ channels in rabbit aorta and CCSM. KMUP-2 (0.2, 0.4, 0.6 mg/kg), similar to KMUP-1 and sildenafil, caused increases of intracavernous pressure (ICP) and duration of tumescene (DT) in a dose-dependent manner. It is concluded that both the increases of cGMP and the opening activity of K+ channels play prominent roles in KMUP-2-induced aortic smooth muscle and CCSM relaxation and increases of ICP in rabbits. Drug Dev. Res. 55:162,172, 2002. © 2002 Wiley-Liss, Inc. [source] Quantifying the evidence for ecological synergiesECOLOGY LETTERS, Issue 12 2008Emily S. Darling Abstract There is increasing concern that multiple drivers of ecological change will interact synergistically to accelerate biodiversity loss. However, the prevalence and magnitude of these interactions remain one of the largest uncertainties in projections of future ecological change. We address this uncertainty by performing a meta-analysis of 112 published factorial experiments that evaluated the impacts of multiple stressors on animal mortality in freshwater, marine and terrestrial communities. We found that, on average, mortalities from the combined action of two stressors were not synergistic and this result was consistent across studies investigating different stressors, study organisms and life-history stages. Furthermore, only one-third of relevant experiments displayed truly synergistic effects, which does not support the prevailing ecological paradigm that synergies are rampant. However, in more than three-quarters of relevant experiments, the outcome of multiple stressor interactions was non-additive (i.e. synergies or antagonisms), suggesting that ecological surprises may be more common than simple additive effects. [source] Impairment due to cannabis and ethanol: clinical signs and additive effectsADDICTION, Issue 6 2010Jørgen G. Bramness ABSTRACT Aims Studies have shown that the impairing effects of ,-9-tetrahydrocannabinol (THC) are dose-related. Cannabis intake increases the risk of traffic accidents. The purpose of this study was to see how different clinical tests and observations were related to blood THC concentrations and to determine whether the combined influence of THC and ethanol was different from either drug alone. Design A retrospective cross-sectional forensic database study. Setting Drivers apprehended by the police suspected of driving under the influence of alcohol other drugs. Participants We investigated 589 cases positive for THC only. In addition, 894 cases with THC and ethanol were included. A comparison was made with 3480 drivers with only ethanol in their blood and 79 drivers who tested negative. Measurements Data were analytical results of blood samples and the 27 clinical tests and observations included in the Norwegian clinical test for impairment (CTI). Findings No relationship was found between blood THC concentration and most of the CTI tests. Blood THC concentration was, however, related to conjunctival injection, pupil dilation and reaction to light and to the overall risk of being judged impaired. When THC and ethanol were detected together the risk of being judged impaired was increased markedly. Conclusions This study demonstrates that cannabis impairs driving ability in a concentration-related manner. The effect is smaller than for ethanol. The effect of ethanol and cannabis taken simultaneously is additive. Conjunctival injection, dilated pupils and slow pupil reaction are among the few signs to reveal THC influence. [source] The impact of cigarette deprivation and cigarette availability on cue,reactivity in smokersADDICTION, Issue 2 2010Steffani R. Bailey ABSTRACT Aims This experiment was conducted to determine the impact of cigarette deprivation and cigarette availability on reactivity measures to cigarette cues. Participants Smokers were recruited who were 18 years of age or older, not attempting to quit or cut down on their smoking, smoked at least 20 cigarettes daily, had been smoking regularly for past year and had an expired carbon monoxide level of at least 10 parts per million. Design Smokers were assigned randomly to abstain from smoking for 24 hours (n = 51) or continue smoking their regular amount (n = 50). Twenty-four hours later, they were exposed to trials of either a lit cigarette or a glass of water with a 0, 50 or 100% probability of being able to sample the cue on each trial. Craving, mood, heart rate, skin conductance, puff topography and latency to access door to sample the cue were measured. Findings Both exposure to cigarette cues and increasing availability of those cues produced higher levels of craving to smoke. Deprivation produced a generalized increase in craving. There was no consistent evidence, however, that even under conditions of high cigarette availability, deprived smokers were sensitized selectively to presentations of cigarette cues. Conclusions The data suggest that, even under conditions of immediate cigarette availability, deprivation and cue presentations have independent, additive effects on self-reported craving levels in smokers. [source] Cytogenetic effects of commercial formulations of deltamethrin and/or isoproturon on human peripheral lymphocytes and mouse bone marrow cellsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2007Lalit K.S. Chauhan Abstract The cytogenetic effects of deltamethrin (DEL) and/or isoproturon (ISO) were examined in human lymphocytes and mouse bone marrow cells. Peripheral lymphocytes were exposed to DEL (2.5, 5, 10, or 20 ,M), ISO (25, 50, 100, or 200,M), or DEL + ISO (2.5 + 25, 5 + 50, 10 + 100, or 20 + 200 ,M) and cytogenic effects were evaluated via chromosomal aberrations (CA) and the cytokinesis-block micronucleus assay (CBMN). Mice were orally gavaged to single dose of DEL (6.6 mg/kg), ISO (670 mg/kg), or DEL+ISO (6.6 + 670 mg/kg) for 24 hr or to DEL (3.3 mg/kg/day), ISO (330 mg/kg/day), or DEL + ISO (3.3 + 330 mg/kg/day) for 30 days and analyzed for CA. DEL induced a significant frequency of CA at 10 ,M whereas ISO (25,100,M) alone, or in combination with DEL, did not show any significant effect. Micronucleus (MN) induction was observed to be concentration-dependent though significant frequencies were observed at 5 ,M DEL, 100 ,M ISO, or 5 + 50 ,M DEL + ISO. In mice, DEL inhibited the mitotic index (MI) significantly (P < 0.001) at 24 hr while ISO alone, or in combination with DEL, did not cause any statistically significant effect. Following a 24 hr exposure, DEL and ISO alone induced significant (P < 0.01) frequencies of CA, whereas DEL + ISO in combination did not. Furthermore, 30 days exposure of ISO significantly inhibited the MI (P < 0.02 or < 0.01) and induced CA while DEL alone, or in combination with ISO, resulted in no significant effect on CA or the MI. The present findings indicate that the in vitro and in vivo exposure of a commercial formulation of DEL can cause genotoxic effects in mammals. However, the coexposure of DEL and ISO did not show additive effects, but instead demonstrated somewhat reduced genotoxicity. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source] New drug combinations for the treatment of murine AIDS and macrophage protectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2001A. Fraternale The failure of highly active antiretroviral therapies (HAART) is mainly due to the existence of latent infected reservoirs, such as macrophages and resting CD4+ T cells. In this paper, we report the results that we obtained in a murine model of AIDS by alternating the administration of the lympholitic drug 2-Fluoro-ara-AMP (Fludarabine) to eliminate the infected cells, with that of Azidothymidine (AZT) plus reduced glutathione (GSH) encapsulated in erythrocytes, to protect lymphocytes and macrophages not yet infected, respectively. Two groups of infected mice were treated as follows: one group was treated by alternating the administration of Fludarabine and AZT (treatment A), while the other group received the same treatment plus GSH-loaded erythrocytes given with AZT (treatment A + L,RBC). Fludarabine was administered intraperitoneally, AZT in the drinking water and GSH was encapsulated in erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. The results obtained show that GSH-loaded erythrocytes provide additive effects in all the parameters examined. Alternation of a lympholitic drug and antiretroviral drug is effective in reducing the progression of murine AIDS. Addition of a system to protect macrophages provides additive effects in almost all the parameters considered, confirming that combination therapies aimed at protecting different infectable cell compartments are better than treatments protecting mainly lymphocytes. [source] Evidence for RPE65-independent vision in the cone-dominated zebrafish retinaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Helia B. Schonthaler Abstract An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11- cis -retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all- trans to 11- cis -retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11- cis -retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all- trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11- cis -retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11- cis -retinal for cone vision. [source] Right-wing authoritarianism, Big Five and perceived threat to safetyEUROPEAN JOURNAL OF PERSONALITY, Issue 2 2010Francesca Dallago Abstract Using structural equations modelling, we performed a secondary analysis of the data collected by the Italian Observatory of the North West (Italian national sample, N,=,976) to investigate the direct, mediated and moderated relations connecting the Big Five personality factors and perceived personal and societal threat to safety with right-wing authoritarianism (RWA). Openness, Conscientiousness and perceived societal threat to safety exerted additive effects on RWA; the relation between Openness and RWA was partially mediated by societal threat to safety and that between societal threat to safety and RWA was moderated by Openness. Limitations and possible developments of this research are discussed. Copyright © 2009 John Wiley & Sons, Ltd. [source] RELATIVE CONTRIBUTION OF ADDITIVE, DOMINANCE, AND IMPRINTING EFFECTS TO PHENOTYPIC VARIATION IN BODY SIZE AND GROWTH BETWEEN DIVERGENT SELECTION LINES OF MICEEVOLUTION, Issue 5 2009Reinmar Hager Epigenetic effects attributed to genomic imprinting are increasingly recognized as an important source of variation in quantitative traits. However, little is known about their relative contribution to phenotypic variation compared to those of additive and dominance effects, and almost nothing about their role in phenotypic evolution. Here we address these questions by investigating the relative contribution of additive, dominance, and imprinting effects of quantitative trait loci (QTL) to variation in "early" and "late" body weight in an intercross of mice selected for divergent adult body weight. We identified 18 loci on 13 chromosomes; additive effects accounted for most of the phenotypic variation throughout development, and imprinting effects were always small. Genetic effects on early weight showed more dominance, less additive, and, surprisingly, less imprinting variation than that of late weight. The predominance of additivity of QTL effects on body weight follows the expectation that additive effects account for the evolutionary divergence between selection lines. We hypothesize that the appearance of more imprinting effects on late body weight may be a consequence of divergent selection on adult body weight, which may have indirectly selected for alleles showing partial imprinting effects due to their associated additive effects, highlighting a potential role of genomic imprinting in the response to selection. [source] EPISTASIS AND DOMINANCE: EVIDENCE FOR DIFFERENTIAL EFFECTS IN LIFE-HISTORY VERSUS MORPHOLOGICAL TRAITSEVOLUTION, Issue 10 2006Derek A. Roff Abstract Dominance and epistatic effects are predicted to be larger in life-history than in morphological traits. We test these predictions using published results from line cross analyses. We find that dominance is found in more than 95% of traits, regardless of the type of trait, but that the magnitude of the effect in relation to the additive effect is much greater in life-history than in morphological traits. Epistatic effects were detected more often in life-history than in morphological traits (79% and 67%, respectively). We also test for a difference in the magnitude of the effects by comparing the ratio of the nonadditive components separately to the additive component. For both dominance and epistatic components, the ratio of the nonadditive component to additive effects in life-history traits is approximately twice as large as that for morphological traits. [source] EVOLUTION OF GENETIC ARCHITECTURE UNDER DIRECTIONAL SELECTIONEVOLUTION, Issue 8 2006Thomas F. Hansen Abstract We investigate the multilinear epistatic model under mutation-limited directional selection. We confirm previous results that only directional epistasis, in which genes on average reinforce or diminish each other's effects, contribute to the initial evolution of mutational effects. Thus, either canalization or decanalization can occur under directional selection, depending on whether positive or negative epistasis is prevalent. We then focus on the evolution of the epistatic coefficients themselves. In the absence of higher-order epistasis, positive pairwise epistasis will tend to weaken relative to additive effects, while negative pairwise epistasis will tend to become strengthened. Positive third-order epistasis will counteract these effects, while negative third-order epistasis will reinforce them. More generally, gene interactions of all orders have an inherent tendency for negative changes under directional selection, which can only be modified by higher-order directional epistasis. We identify three types of nonadditive quasi-equilibrium architectures that, although not strictly stable, can be maintained for an extended time: (1) nondirectional epistatic architectures; (2) canalized architectures with strong epistasis; and (3) near-additive architectures in which additive effects keep increasing relative to epistasis. [source] EFFECTS OF GENETIC DRIFT ON VARIANCE COMPONENTS UNDER A GENERAL MODEL OF EPISTASISEVOLUTION, Issue 10 2004N.H. Barton Abstract We analyze the changes in the mean and variance components of a quantitative trait caused by changes in allele frequencies, concentrating on the effects of genetic drift. We use a general representation of epistasis and dominance that allows an arbitrary relation between genotype and phenotype for any number of diallelic loci. We assume initial and final Hardy-Weinberg and linkage equilibrium in our analyses of drift-induced changes. Random drift generates transient linkage disequilibria that cause correlations between allele frequency fluctuations at different loci. However, we show that these have negligible effects, at least for interactions among small numbers of loci. Our analyses are based on diffusion approximations that summarize the effects of drift in terms of F, the inbreeding coefficient, interpreted as the expected proportional decrease in heterozygosity at each locus. For haploids, the variance of the trait mean after a population bottleneck is var(,z,) =where n is the number of loci contributing to the trait variance, VA(1)=VA is the additive genetic variance, and VA(k) is the kth-order additive epistatic variance. The expected additive genetic variance after the bottleneck, denoted (V*A), is closely related to var(,z,); (V*A) (1 ,F)Thus, epistasis inflates the expected additive variance above VA(1 ,F), the expectation under additivity. For haploids (and diploids without dominance), the expected value of every variance component is inflated by the existence of higher order interactions (e.g., third-order epistasis inflates (V*AA)). This is not true in general with diploidy, because dominance alone can reduce (V*A) below VA(1 ,F) (e.g., when dominant alleles are rare). Without dominance, diploidy produces simple expressions: var(,z,)==1 (2F) kVA(k) and (V*A) = (1 ,F)k(2F)k-1VA(k) With dominance (and even without epistasis), var(,z,)and (V*A) no longer depend solely on the variance components in the base population. For small F, the expected additive variance simplifies to (V*A)(1 ,F) VA+ 4FVAA+2FVD+2FCAD, where CAD is a sum of two terms describing covariances between additive effects and dominance and additive × dominance interactions. Whether population bottlenecks lead to expected increases in additive variance depends primarily on the ratio of nonadditive to additive genetic variance in the base population, but dominance precludes simple predictions based solely on variance components. We illustrate these results using a model in which genotypic values are drawn at random, allowing extreme and erratic epistatic interactions. Although our analyses clarify the conditions under which drift is expected to increase VA, we question the evolutionary importance of such increases. [source] A common cortactin gene variation confers differential susceptibility to severe asthmaGENETIC EPIDEMIOLOGY, Issue 8 2008Shwu-Fan Ma Abstract Genomic regions with replicated linkage to asthma-related phenotypes likely harbor multiple susceptibility loci with relatively minor effects on disease susceptibility. The 11q13 chromosomal region has repeatedly been linked to asthma with five genes residing in this region with reported replicated associations. Cortactin, an actin-binding protein encoded by the CTTN gene in 11q13, constitutes a key regulator of cytoskeletal dynamics and contractile cell machinery, events facilitated by interaction with myosin light chain kinase; encoded by MYLK, a gene we recently reported as associated with severe asthma in African Americans. To evaluate potential association of CTTN gene variation with asthma susceptibility, CTTN exons and flanking regions were re-sequenced in 48 non-asthmatic multiethnic samples, leading to selection of nine tagging polymorphisms for case-control association studies in individuals of European and African descent. After ancestry adjustments, an intronic variant (rs3802780) was significantly associated with severe asthma (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.20,2.43; p=0.003) in a joint analysis. Further analyses evidenced independent and additive effects of CTTN and MYLK risk variants for severe asthma susceptibility in African Americans (accumulated OR: 2.93, 95% CI: 1.40,6.13, p=0.004). These data suggest that CTTN gene variation may contribute to severe asthma and that the combined effects of CTTN and MYLK risk polymorphisms may further increase susceptibility to severe asthma in African Americans harboring both genetic variants. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Phosphorylation by COP9 Signalosome-Associated CK2 Promotes Degradation of p27 during the G1 Cell Cycle PhaseISRAEL JOURNAL OF CHEMISTRY, Issue 2 2006Xiaohua Huang The cell cycle regulator p27Kip1 (p27) is controlled by 26S proteasome-mediated proteolysis by two different pathways. From the S till the G2 phase of the cell cycle, degradation of p27 takes place in the nucleus and is initiated by CDK2-dependent phosphorylation of threonine 187 with subsequent ubiquitination by the SCFSkp2 ubiquitin ligase. During the G1 cell cycle phase (G1), p27 breakdown is cytosolic and is initiated by nuclear export with subsequent ubiquitination by a RING finger ligase called kip1 ubiquitination complex. Here we show that the COP9 signalosome (CSN) is a regulator of p27 proteolysis during G1. The CSN interacts with p27 and the CSN-associated kinase CK2 phosphorylates p27 at two regions. One is central to the protein (amino acids 101,113), and the other was mapped near to the C-terminus (amino acids 170,189). Elimination of the putative C-terminal phosphorylation sites stabilizes ectopic p27 towards proteasomal degradation and abolishes CSN,p27 binding. Inhibition of CSN-associated kinase activity by curcumin attenuates loss of p27 upon cell cycle re-entry. Similar but not additive effects of the phosphoinositol-3-kinase blocker LY 290042 may point to a common pathway of CSN-associated CK2 and protein kinase B/Akt (Akt) in regulating p27 abundance. Akt is found in Flag pulldowns of lysates obtained from cells permanently expressing Flag-tagged CSN2, indicating that Akt is a novel kinase associated with the CSN. Thus, the CSN seems to regulate p27 proteolysis at G1 downstream of Ras-mediated signal pathways. [source] Diet and Its Relationship with Grip Strength in Community-Dwelling Older Men and Women: The Hertfordshire Cohort StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2008Sian M. Robinson PhD OBJECTIVES: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships. DESIGN: Cross-sectional and retrospective cohort study. SETTING: Hertfordshire, United Kingdom. PARTICIPANTS: Two thousand nine hundred eighty-three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom. MEASUREMENTS: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer. RESULTS: Grip strength was positively associated with height and weight at birth and inversely related to age (all P<.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43 kg (95% confidence interval (CI)=0.13,0.74) in men (P=.005) and 0.48 kg (95% CI=0.24,0.72) in women (P<.001) was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age, and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength. CONCLUSION: These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the antiinflammatory actions of omega-3 fatty acids may play a role in the prevention of sarcopenia. [source] Estimates of genetic parameters for Boran, Friesian, and crosses of Friesian and Jersey with the Boran cattle in the tropical highlands of Ethiopia: milk production traits and cow weightJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 3 2004S. Demeke Summary Breed additive and non-additive effects plus heritabilities and repeatabilities for milk yield per lactation (LMY), milk yield per day (DMY), lactation length (LL), annual milk yield (AMY), annual milk yield per metabolic body weight (AMYBW) and cow weight at calving (BW) were estimated for 5464 lactation records collected from purebred Boran (B), Friesian (F), and crosses of Friesian and Jersey (J) breeds with the Boran breed raised in the tropical highlands of Ethiopia. Single trait analysis was carried out by using two equivalent repeatability animal models. In the first model the genotype was fitted as a fixed group effect, while in the second model the genotype was substituted by breed additive, heterotic and recombination effects fitted as fixed covariates. Both the F and J breed additive effects, measured as a deviation from the B breed were significant (p < 0.01) for all traits, except for BW of the J. The F and J additive contributions were 2774 ± 81 and 1473 ± 362 kg for LMY, 7.1 ± 0.2 and 4.8 ± 0.8 kg for DMY, 152 ± 7 and 146 ± 31 days for LL, 2345 ± 71 and 1238 ± 319 kg for AMY, 20.6 ± 0.9 and 18.9 ± 4.3 kg for AMYBW, and 140 ± 4 and ,21 ± 22 kg (p > 0.05) for BW. The heterotic contributions to the crossbred performance were also positive and significant (p < 0.01) for all traits. The F1 heterosis expressed as a deviation from the mid-parent values were 22 and 66% for LMY, 11 and 20% for DMY, 29 and 29% for LL, 21 and 64% for AMY, 42 and 42% for AMYBW, and 2% (p < 0.05) and 11% for BW for the F × B and J × B crosses, respectively. The recombination effect estimated for the F × B crosses was negative and significant for LMY (,526 ± 192 kg, p < 0.01), DMY (,3.0 ± 0.4 kg, p < 0.001), AMY (,349 ± 174 kg, p < 0.05) and BW (,68 ± 11 kg, p < 0.001). For the J × B crosses the recombination loss was significant and negative only for DMY (,2.2 ± 0.7 kg, p < 0.05) and BW (,33 ± 17 kg, p < 0.05). The direct heritabilities (h2) estimated for LMY, DMY, LL, AMY and AMYBW were 0.24 ± 0.04, 0.19 ± 0.03, 0.13 ± 0.03, 0.23 ± 0.04 and 0.17 ± 0.05, respectively. Based on the genetic parameters estimated, the best breeding strategy to increased milk production under highland Ethiopian conditions is to apply selection on purebred base populations (Boran and Friesian) and then crossing them to produce F1 dairy cows. However, for breeding decision based on total dairy merit, further investigations are needed for traits such as milk quality, reproduction, longevity and survival. Zusammenfassung Additive Rasseneffekte, nicht additive Effekte, Heritabilitäten und Wiederholbarkeiten für Milchmenge pro Laktation (LMY), Milchmenge pro Tag (DMY), Laktationsdauer (LL), jährliche Milchmenge (AMY), jährliche Milchmenge pro metabolischem Körpergewicht (AMYBW) und Kuhgewichte zur Kalbung (BW) wurden anhand von 5464 Laktationsdatensätzen von reinrassigen Boran (B), Friesian (F) und Kreuzungen der Rassen Friesian und Jersey (J) mit der Rasse Boran, die im tropischen Hochland von Äthiopien groß gezogen wurden, geschätzt. Einmerkmalsmodelle wurden mit zwei äquivalenten Wiederholbarkeits-Tiermodellen durchgeführt. Im ersten Modell wurde der Genotyp als fixer Gruppeneffekt berücksichtigt, während im zweiten Modell der Genotyp durch additive Rasseneffekte, Heterosis und Rekombinationseffekte als Kovariable ersetzt wurde. Die additiven Rasseneffekte von F und J, gemessen als Abweichung von der Rasse B, waren für alle Merkmale signifikant (p < 0,01), ausgenommen BW für die Rasse J. Die additiven Rasseneffekte von F und J betrugen 2774 ± 81 und 1473 ± 362 kg für LMY, 7,1 ± 0,2 und 4,8 ± 0,8 kg für DMY, 152 ± 7 und 146 ± 31 Tage für LL, 2345 ± 71 und 1238 ± 319 kg für AMY, 20,6 ± 0,9 und 18,9 ± 4,3 kg für AMYBW und 140 ± 4 und ,21 ± 22 kg (p > 0,05) für BW. Die Heterosis bei den Kreuzungstieren war positiv und signifikant für alle Merkmale (p < 0,01). Die Heterosis der F1 -Tiere, ausgedrückt als Abweichung vom Mittel der beiden Eltern, betrug 22 und 66% für LMY, 11 und 20% für DMY, 29 und 29% für LL, 21 und 64% für AMY, 42% und 42% für AMYBW und 2% (p < 0,05) und 11% für BW für die F × B und J × B Kreuzungen. Der geschätzte Rekombinationseffekt für die F × B Kreuzungen war negativ und signifikant für LMY (,526 ± 192 kg, p < 0,01), DMY (,3,0 ± 0,4 kg, p < 0,001), AMY (,349 ± 174, p < 0,05) und BW (,68 ± 11 kg, p < 0,001). Für die J × B Kreuzungen war der Rekombinationsverlust signifikant und negativ nur für DMY (,2,2 ± 0,7 kg, p < 0,05) und BW (,33 ± 17, p < 0,05). Die geschätzten Heritabilitäten (h2) betrugen für LMY, DMY, LL, AMY und AMYBW 0,24 ± 0,04, 0,19 ± 0,03, 0,13 ± 0,03, 0,23 ± 0,04 und 0,17 ± 0,05. Basierend auf den geschätzten genetischen Parametern erscheint Selektion in den Reinzuchtpopulationen B und F und anschließ end Kreuzung dieser Tiere zur Erstellung von F1 -Milchkühen als günstigste Zuchtstrategie, um die Milchproduktion unter äthiopischen Hochlandbedingungen zu steigern. Für Zuchtentscheidungen, die die gesamte Milchproduktion berücksichtigen, sind weitere Untersuchungen notwendig für Merkmale wie Milchqualität, Reproduktion, Persistenz und Langlebigkeit. [source] Synergistic, antagonistic and additive effects of multiple stressors: predation threat, parasitism and pesticide exposure in Daphnia magnaJOURNAL OF APPLIED ECOLOGY, Issue 6 2008Anja Coors Summary 1Predation and parasitism are important factors in the ecology and evolution of natural populations and may, along with other environmental factors, interact with the impact of anthropogenic pollutants. 2Our study aimed at identifying potential interactions between three stressors (predation threat, parasitism and pesticide exposure) and at exploring the predictability of their joint effects by using the model of independent action. We assessed in a full-factorial design the impacts of these stressors on key life-history traits and population growth rate of the water flea Daphnia magna. 3When applied as single stressors, predation threat and parasite challenge induced varying stressor-specific adaptive responses. The pesticide carbaryl was applied at a generally sublethal concentration, which caused low mortality only in first-brood offspring. 4Pesticide exposure interacted synergistically with parasite challenge regarding survival, which suggests immunomodulatory activity of the pesticide. Predation threat by phantom midge larvae showed antagonistic interactions for amount of first-brood offspring with both parasite challenge and carbaryl exposure. All stressors additively affected age and size at maturity, which added up to a considerable delay in the onset of reproduction in the three-stressor combination. The intrinsic rate of natural increase, r, reflected the non-additive and additive effects on single endpoints and showed significant synergistic interactions for all two-stressor combinations. The combination of all stressors resulted in a dramatic reduction of r compared to the stressor-free control. 5The model of independent action proved useful in quantitatively predicting effects of additively acting stressors, and in visualizing the occurrence and magnitude of non-additive effects in accordance with results of analysis of variances. 6Synthesis and applications. Cumulative additive effects and non-additive interactions of natural antagonists and pollutants are shown to result in considerable impacts on ecologically relevant parameters. As a starting point for an environmentally more realistic risk assessment of chemicals, it may be a valuable strategy to screen for non-additive effects among many stress factors simultaneously in simplified experimental designs by using the model of independent action. [source] The joint effects of larval density and 14C-cypermethrin on the life history and population growth rate of the midge Chironomus ripariusJOURNAL OF APPLIED ECOLOGY, Issue 6 2003Helen L. Hooper Summary 1Chemical effects on organisms are typically assessed using individual-level endpoints or sometimes population growth rate (PGR), but such measurements are generally made at low population densities. In contrast most natural populations are subject to density dependence and fluctuate around the environmental carrying capacity as a result of individual competition for resources. As ecotoxicology aims to make reliable population projections of chemical impacts in the field, an understanding of how high-density or resource-limited populations respond to environmental chemicals is essential. 2Our objective was to determine the joint effects of population density and chemical stress on the life history and PGR of an important ecotoxicological indicator species, Chironomus riparius, under controlled laboratory conditions. Populations were fed the same ration but initiated at different densities and exposed to a solvent control and three concentrations of 14C-cypermethrin in a sediment,water test system for 67 days at 20 ± 1 °C. 3Density had a negative effect on all the measured life-history traits, and PGR declined with increasing density in the controls. Exposure to 14C-cypermethrin had a direct negative effect on juvenile survival, presumably within the first 24 h because the chemical rapidly dissipated from the water column. Reductions in the initial larval densities resulted in an increase in the available resources for the survivors. Subsequently, exposed populations emerged sooner and started producing offspring earlier than the controls. 14C-cypermethrin had no effect on estimated fecundity and adult body weight but interacted with density to reduce the time to first emergence and first reproduction. As a result, PGR increased with cypermethrin concentration when populations were initiated at high densities. 4Synthesis and applications. The results showed that the effects of 14C-cypermethrin were buffered at high density, so that the joint effects of density and chemical stress on PGR were less than additive. Low levels of chemical stressors may increase carrying capacity by reducing juvenile competition for resources. More and perhaps fitter adults may be produced, similar to the effects of predators and culling; however, toxicant exposure may result in survivors that are less tolerant to changing conditions. If less than additive effects are typical in the field, standard regulatory tests carried out at low density may overestimate the effects of environmental chemicals. Further studies over a wide range of chemical stressors and organisms with contrasting life histories are needed to make general recommendations. [source] Renal, vascular and cardiac fibrosis in rats exposed to passive smoking and industrial dust fibre amositeJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 11-12 2009Peter Boor Abstract Passive smoking is an independent risk factor for cardiovascular diseases. Industrial fibrous dust, e.g. the asbestos group member, amosite, causes lung cancer and fibrosis. No data are available on renal involvement after inhalational exposure to these environmental pollutants or of their combination, or on cardiovascular and renal toxicity after exposure to amosite. Male Wistar rats were randomized into four groups (n= 6): control and amosite group received initially two intratracheal instillations of saline and amosite solution, respectively. Smoking group was subjected to standardized daily exposure to tobacco smoke for 2 hrs in a concentration resembling human passive smoking. Combined group was exposed to both amosite and cigarette smoke. All rats were killed after 6 months. Rats exposed to either amosite or passive smoking developed significant glomerulosclerosis and tubulointerstitial fibrosis. Combination of both exposures had additive effects. Histomorphological changes preceded the clinical manifestation of kidney damage. In both groups with single exposures, marked perivascular and interstitial cardiac fibrosis was detected. The additive effect in the heart was less pronounced than in the kidney, apparent particularly in changes of vascular structure. Advanced oxidation protein products, the plasma marker of the myeloperoxidase reaction in activated monocytes/macrophages, were increased in all exposed groups, whereas the inflammatory cytokines did not differ between the groups. In rats, passive smoking or amosite instillation leads to renal, vascular and cardiac fibrosis potentially mediated via increased myeloperoxidase reaction. Combination of both pollutants shows additive effects. Our data should be confirmed in subjects exposed to these environmental pollutants, in particular if combined. [source] Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP-2JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2002Takahito Yuasa The roles of Sonic hedgehog (Shh) and Bone morphogenetic protein-2 (Bmp-2) in osteoblast differentiation were investigated using in vitro cell systems. Recombinant amino-terminal portion of SHH (rSHH-N) dose dependently stimulated ALP activity in C3H10T1/2 and MC3T3-E1 cells. rSHH-N induced expression of Osteocalcin mRNA in C3H10T1/2 cells. A soluble form of the receptor for type IA BMP receptor antagonized rSHH-N-induced ALP activity in C3H10T1/2 and MC3T3-E1 cells, indicating that BMPs are involved in SHH-induced osteoblast differentiation. Simultaneous supplement with rSHH-N and BMP-2 synergistically induced ALP activity and expression of Osteocalcin mRNA in C3H10T1/2 cells. Pretreatment with rSHH-N for 6 h enhanced the response to BMP-2 by increasing ALP activity in C3H10T1/2 and MC3T3-E1 cells. Stimulatory effects of rSHH-N and additive effects with rSHH-N and BMP-2 on ALP activity were also observed in mouse primary osteoblastic cells. Transplantation of BMP-2 (1 ,g) into muscle of mice induced formation of ectopic bone, whereas transplantation of r-SHH-N (1,5 ,g) failed to generate it. These results indicate that Shh plays important roles in osteoblast differentiation by cooperating with BMP. © 2002 Wiley-Liss, Inc. [source] Inheritance of song and stridulatory peg number divergence between Chorthippus brunneus and C. jacobsi, two naturally hybridizing grasshopper species (Orthoptera: Acrididae)JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2005C. I. SALDAMANDO Abstract Knowledge of the genetic basis of divergence in mating signal characters that contribute to reproductive isolation is critical to understanding speciation. Here, we describe a semi-automated system for characterizing grasshopper acoustic signals. We used this system to study the genetic basis of divergence in three male calling song components [echeme (EL), syllable (SL) and phrase (PL) lengths] between Chorthippus brunneus and C. jacobsi, two species of grasshoppers that hybridize in northern Spain. We also studied the number of pegs in the stridulatory file. For all characters, additive effects accounted for most of the genetic differentiation between species. However, the three song components also showed small but significant epistatic effects. No sex linkage was detected. Wright,Castle,Lande estimates of the minimum numbers of genetic factors underlying song and peg number divergence were low: peg number (ne = 5.87 ± 5.84), SL (ne = 2.37 ± 4.79) and PL (ne = 0.87 ± 0.86). On the other hand, EL appeared to be controlled by many genes. These results suggest that divergence in SL and PL might be driven by sexual selection whereas EL might not be under selection. This is consistent with experimental results on female song preference in related species. However, the fact that few factors appear to underlie the differences in peg number is surprising. Peg number is not closely related to song characteristics. It often varies between closely related grasshopper species and it has been assumed to be a neutral character. The biometrical approaches used here tend to underestimate the number of factors influencing a trait but provide valuable background for subsequent quantitative trait loci analyses. [source] Evaluation of Garam Masala Spices and Phosphates as Antioxidants in Cooked Ground BeefJOURNAL OF FOOD SCIENCE, Issue 5 2006Mihir N. Vasavada ABSTRACT:, This study determined antioxidant effects and sensory attributes of individual ingredients (black pepper, caraway, cardamom, chili powder, cinnamon, cloves, coriander, cumin, fennel, ginger, nutmeg, salt, star anise) of an Indian spice blend (garam masala) in cooked ground beef. Thiobarbituric acid (TBA) values were measured as an indicator of rancidity for cooked samples on 1-, 8-, or 15-d refrigerated storage. Cooked samples were evaluated by a trained panel (n= 13) for the intensity of rancid odor/flavor, beef flavor, and spice flavor and correlated with TBA values of same day samples. We also investigated possible additive effects between spice antioxidants and iron binding (type II) antioxidants on lipid oxidation by measuring TBA values. All spices had antioxidant effects on cooked ground beef, compared to controls. Among spices, cloves were the most effective in controlling lipid oxidation, with TBA values of 0.75, after 15-d refrigerated storage. All spices at their recommended levels lowered rancid odor and flavor in cooked ground beef, compared to controls. As expected, most spices also imparted distinctive flavors to cooked ground beef. There was a positive correlation (0.77) between TBA values on 15-d refrigerated storage and rancid odor/flavor. Type II antioxidants (iron-binding phosphate compounds) were more effective than individual type I antioxidants (spices and butylated hydroxytoluene; BHT) for maintenance of low TBA values in cooked ground beef during storage. Additive effects were observed with rosemary + milk mineral or sodium tripolyphosphate (STP) compared to rosemary alone. [source] Mixture Interpretation: Defining the Relevant Features for Guidelines for the Assessment of Mixed DNA Profiles in Forensic Casework,JOURNAL OF FORENSIC SCIENCES, Issue 4 2009Bruce Budowle Ph.D. Abstract:, Currently in the United States there is little direction for what constitutes sufficient guidelines for DNA mixture interpretation. While a standardized approach is not possible or desirable, more definition is necessary to ensure reliable interpretation of results is carried out. In addition, qualified DNA examiners should be able to review reports and understand the assumptions made by the analyst who performed the interpretation. Interpretation of DNA mixture profiles requires consideration of a number of aspects of a mixed profile, many of which need to be established by on-site, internal validation studies conducted by a laboratory's technical staff, prior to performing casework analysis. The relevant features include: criteria for identification of mixed specimens, establishing detection and interpretation threshold values, defining allele peaks, defining nonallele peaks, identifying artifacts, consideration of tri-allelic patterns, estimating the minimum number of contributors, resolving components of a mixture, determining when a portion of the mixed profile can be treated as a single source profile, consideration of potential additive effects of allele sharing, impact of stutter peaks on interpretation in the presence of a minor contributor, comparison with reference specimens, and some issues related to the application of mixture calculation statistics. Equally important is using sensible judgment based on sound and documented principles of DNA analyses. Assumptions should be documented so that reliable descriptive information is conveyed adequately concerning that mixture and what were the bases for the interpretations that were carried out. Examples are provided to guide the community. Interpretation guidelines also should incorporate strategies to minimize potential bias that could occur by making inferences based on a reference sample. The intent of this paper is to promote more thought, provide assistance on many aspects for consideration, and to support that more formalized mixture interpretation guidelines are developed. [source] Simulated driving performance following prolonged wakefulness and alcohol consumption: separate and combined contributions to impairmentJOURNAL OF SLEEP RESEARCH, Issue 3 2000Arnedt The separate and combined effects of prolonged wakefulness and alcohol were compared on measures of subjective sleepiness, simulated driving performance and drivers' ability to judge impairment. Twenty-two males aged between 19 and 35 years were tested on four occasions. Subjects drove for 30 min on a simulated driving task under conditions determined by the factorial combination of 16 and 20 h of wakefulness and blood alcohol concentrations of 0.00 and 0.08%. The simulated driving session took place 30 min postingestion; subjects in the two alcohol conditions participated in a second 30-min driving session 90-min postingestion. Subjects made simultaneous ratings of their impairment while driving and retrospective ratings at the end of each test session. Subjective sleepiness measures were completed before and after each driving session. The combination of 20 h of prolonged wakefulness and alcohol produced significantly lower ratings of subjective sleepiness and driving performance that was worse, but not significantly so, than would be expected from the additive effects of each condition alone. Driving performance was always worse in the second driving session, during the elimination phase of alcohol metabolism, despite blood alcohol concentrations being lower than during the first driving session. There was a modest association between perceived and actual impairments in driving performance following prolonged wakefulness and alcohol. The findings suggest that the combination of prolonged wakefulness and alcohol consumption produced greater decrements in simulated driving performance than each condition alone and that drivers have only a modest ability to appreciate the magnitude of their impairment. 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