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Preliminary investigation of the direct and moderating effects of family and individual variables on the adjustment of children and adolescents with diabetes.

Investigated the direct and stress-moderating effects of mother and child coping skills, child Type A behavior, and mother's report of disease-related family interruption on both psychological and physiological adjustment in 64 children with insulin-dependent diabetes. Using hierarchical multiple regression analyses, relevant demographic variables (age, gender, disease duration) were first evaluated for effects on the outcome measures, followed by the stress variable, the individual difference and family factors, and the interaction term. Several direct relationships between demographic, individual and family factors, and outcome were identified, as well as one moderating relationship. Implications for research design and future study of children and adolescents with diabetes are discussed.

Adaptation, Psychological↗

Individual variability in homocysteine response to folate depletion: an unusual case.

Research within the past decade has shown that even moderately elevated plasma homocysteine concentrations are associated with increased risk of vascular disease. A variety of genetic and nutritional factors can affect homocysteine concentrations, with folate nutriture being one of the most influential. Plasma homocysteine responses of healthy adults to folate depletion and repletion vary substantially, even when many nutritional and lifestyle factors are normalized in a metabolic unit. The case of a woman with a highly exaggerated homocysteine response to moderate folate depletion is presented. A variety of possible factors relating to homocystine metabolism are discussed, yet no convincing explanation for the unusual pattern is apparent. The case demonstrates that the homocysteine response to folate can be highly variable between individuals, and suggests that further research on the genetic determinants of the human folate requirement is warranted.

Adult↗

Intra-individual variability and influence of urine collection period on dextromethorphan metabolic ratios in healthy subjects.

The aim of the study was to evaluate intra-individual variability in metabolic ratios (MRs) of dextromethorphan (DM) in healthy volunteers and to compare the MRs in urine collected 0-4, 0-8 and 0-24 h post-dose. Urinary molar ratios of DM to dextrorphan (MR1) and of DM to methoxymorphinan (MR2) were obtained after a single oral 27.5 mg dose of DM hydrobromide to ten healthy male and four female Caucasians (ten extensive metabolizers (EM) and four poor metabolizers (PM) of DM) to probe activities of CYP2D6 and CYP3A, respectively. Seven EM and one PM received DM on three additional occasions within 2 months. For the seven EM, the intra-individual variability (CVw) in the MRs obtained in the three urine collections ranged from 11 to 93% (MR1) and from 8 to 77% (MR2). The mean CVw estimated separately for the 4, 8 and 24 h urines by two-way analysis of variance reached 58, 57 and 44% for the MR1 and 50, 42 and 31% for the MR2, respectively. For all 14 subjects, the log-transformed ratios (MR1) obtained in the 24 h urines were highly correlated with those in either the 8 h (rs = 0.967, P < 0.0001) or 4 h urines (rs = 0.946, P < 0.0001). Correlation between the log-transformed MR2s were weaker (24 h vs. 8 h: rs = 0.829, P < 0.0001, 24 h vs. 4 h: rs = 0.831, P < 0.0001). The MR1s in 4 h and 8 h urines were only 2 and 9% less than those in 24 h urines (median differences) and varied from 48 and 47% below to 85 and 55% above (95% -CI for the differences). However, the MR2s in the 4 h and 8 h urines were shifted towards higher values by 49 and 23% and the corresponding 95% -CI limits were: 16-164% (4 h vs. 24 h) and 30-119% (8 h vs. 24 h). In conclusion, MR1 values in the 4 h urine collection agree well with those in longer collections and their use in epidemiological studies can be recommended. The intra-individual variability of approximately 50% in the MR1 has to be taken into account in clinical studies with within-subject design. Accurate determination of the MR2 requires at least a 24 h period of urine collection.

Aryl Hydrocarbon Hydroxylases↗

Inter-individual and intra-individual variability in TNF-alpha production by human peripheral blood cells in vitro.

BACKGROUND: Two assays--isolated peripheral blood mononuclear cells (PBMC) and a whole blood assay (WBA)--are commonly used to study TNF-alpha production by an individual in order to distinguish between high and low cytokine producers. We assessed the reliability and reproducibility of these assays. METHODS: The PBMC assays (n=5) were performed weekly over a period of 6 weeks and the WBAs (n=4) weekly over a 4-week period. Polymethylmethacrylate particles (approx. 6 x 10(2) particles/cell) and optimal concentrations of endotoxin (6.25 and 12.5 ng/ml) were used as the stimulatory agents in PBMC and WBAs, respectively. TNF-alpha production was measured by ELISA. RESULTS: There was a high degree of both intra- and inter-individual variability of TNF-alpha secretion, with unpredictable changes in the amount of the cytokine produced by cells from the same donor. This variability could not be eliminated by correcting for cell numbers. CONCLUSION: The PBMC and WBA models of TNF-alpha production by human peripheral blood cells cannot be used for the evaluation of inter-individual variability in cytokine secretion due to the high intra-individual variability observed. In the case of PBMC this is partly due to differences in the confluency of the cells between individuals.

Adult↗

Short-term intra-individual variability in heidelberg retina tomograph II.

We determined the short-term intra-individual variability for each parameter of the Heidelberg Retina Tomograph II (HRT II). Therefore we examined prospectively 20 healthy volunteers 3 times within 2 weeks. The variability was expressed as the coefficient of variation for each parameter. The short-term intra-individual variability in normal subjects was < or = 12% in all but 3 parameters. Rim Area was the least variable parameter (2 +/- 1%). Cup Volume had the highest variability (25 +/- 38%).

Adult↗

Synaptic Mitochondrial Oxidative Stress Contributes to Individual Variability in Age-Related Cognitive Inflexibility in Mice.

Aging is associated with impairments in cognitive flexibility, a key executive function supported by the medial prefrontal cortex (mPFC), yet the biological mechanisms underlying individual variability in age-related decline remain poorly understood. Here we investigated behavioral, ultrastructural, and proteomic correlates of cognitive inflexibility in mice across aging. Using a touchscreen-based attentional set-shifting task, we observed substantial individual variability in cognitive inflexibility among aged C57BL/6J mice. Volume electron microscopy of the mPFC revealed age-related reductions in synaptic density, but these structural changes did not correlate with cognitive performance. Instead, the proportion of synapses containing presynaptic mitochondria was inversely associated with cognitive flexibility in aged mice. To identify molecular correlates, we performed proteomic profiling of mPFC whole tissue and synaptosome fractions. Proteins associated with individual variability in cognitive inflexibility were largely distinct from those associated with chronological aging. Notably, synaptosomal proteins negatively correlated with cognitive performance were strongly enriched for mitochondrial pathways, including oxidative phosphorylation, mitochondrial translation, and the tricarboxylic acid cycle. Consistent with these findings, the mitochondria-targeted antioxidant MitoQ improved attentional set-shifting performance in aged mice without affecting initial learning. Proteomic analyses revealed that MitoQ reduced the abundance of synaptosomal mitochondrial proteins, particularly those involved in mitochondrial apoptotic signaling. Together, these results suggest that synaptic mitochondrial oxidative stress in the mPFC contributes to individual vulnerability to cognitive inflexibility. Targeting synaptic mitochondrial oxidative stress may therefore represent a promising strategy to preserve executive function during aging.

Animals↗

Inter- and intra-individual variability of ethanol pharmacokinetics over a long period of time.

In most research, the inter- and intra-individual variability of time profiles of ethanol concentration has been studied over a relatively short period of time. We present a study of inter- and intra-individual variability of ethanol pharmacokinetics in five healthy volunteers (social drinkers) over a period of around eight years. The volunteers received a dose of 0.7 g/kg (men) and 0.6 g/kg (women) of ethanol in the form of vodka diluted with mineral water. The blood ethanol concentrations in a series of samples were measured by gas chromatography. For pharmacokinetic calculations, a model with first-order absorption and Michaelis-Menten elimination was applied. A linear regression technique was used to calculate Widmark's coefficient. The area under the concentration-time curve (AUC) was calculated by trapezoid rule. A tendency for pharmacokinetic parameters to alter during the study time was observed, however, these changes were random and did not correlate with the duration of the study. The highest inter- and intra-subject variability of the half time of absorption was observed. The maximal elimination velocity and Michaelis-Menten constant were also very unstable; coefficients of variation were 55.8% and 79.0%, respectively. Other calculated pharmacokinetic parameters (AUC, beta60, V/F, Cmax) were characterized by a lower variability with a coefficient of variation around 36%. Back extrapolation of plasma ethanol concentration using mean value of beta60 for each subject showed that results could be underestimated up to 26% or overestimated up to 102%.

Adult↗

Are all dilemmas in gerontology being swept under the carpet of intra-individual variability?

It is considered that there are great differences among elderly individuals, because the intra-individual variability is great. The differences among specific individuals grow with their age, so when adults reach a very old age, it seems that there are great differences among them--some are able to do some work, the others are not so able-bodied, whereas among high school students there is usually little difference in their physical ability. The research that supports the above mentioned points, however, does not exist and this opinion came about as a result of deduction. The goal of this study is to examine the fluctuations in the elderly and prove that the genetic difference plays a bigger role than the variability, as the intra-individual (or the between-person) variability is present everywhere, not only in very old people.

Aged↗

Hypercholesterolemia in the rabbit induced by feeding graded amounts of low-level cholesterol. Methodological considerations regarding individual variability in response to dietary cholesterol and development of lesion type.

While a number of studies have presented detailed examinations of lesion development in the cholesterol-fed rabbit, individual variability in response to cholesterol feeding and type of lesion produced relative to the degree of cholesterol exposure is not well defined. This study analyzed such critical parameters in an attempt to further characterize the model and establish a baseline for future testing of treatments targeted at limiting atherosclerosis. For these experiments, male New Zealand White rabbits were fed atherogenic diets consisting of 0.05%, 0.10%, 0.15%, 0.20%, or 0.25% cholesterol dissolved in 6% peanut oil for 31 to 32 weeks. Raising dietary cholesterol from 0.05% to 0.15% resulted in a less than twofold stepwise increase in total plasma cholesterol (TPC) exposure (area under plasma cholesterol versus time curve), whereas further increases in cholesterol intake resulted in an exponential four- to fivefold increase in TPC exposure. Regression analysis of TPC exposure with aortic sudanophilia demonstrated a threshold of approximately 5000 cholesterol weeks; below this limit lesions were minimal, and above this value the degree of plaque correlated with TPC exposure. Furthermore, a wide biological variability occurred among rabbits with respect to individual responsiveness to dietary cholesterol. In the aorta, various types of plaques, from fatty streaks to atheromatous lesions, were observed, depending on the degree of cholesterol intake. Diets consisting of < 0.15% cholesterol resulted in the development of fatty streak lesions, while transitional lesions and atheromatous plaques were mostly found with higher cholesterol feeding. Coronary artery atherosclerosis was present in > 50% of animals fed diets > or = 0.15% cholesterol. Despite the level of TPC exposure, coronary lesions in epicardial vessels were generally the fibrous type, whereas intramyocardial arteries demonstrated predominantly intimal foam cells. In conclusion, by adjusting dietary cholesterol intake and selecting rabbits with a similar responsiveness to cholesterol, the overall cholesterol exposure can be more closely controlled to minimize the inherent individual variability among animals in this model. The nature of the target lesion must also be carefully considered, because the efficacy of some treatments may depend on the type of atherosclerotic plaque.

Animals↗

The Eating Attitudes Test (EAT) in Turkish university students: relationship with sociodemographic, social and individual variables.

OBJECTIVE: The primary purpose of this study was to establish the frequency of abnormal eating attitudes and behaviours, as measured by the Eating Attitude Test (EAT 40) in a sample of Turkish university students and to examine the relationship of such abnormalities to socio economic status, social and individual variables. METHOD: The EAT 40, two other questionnaires and a personal data sheet were administered to a sample of 253 female undergraduates at Bogazici and Marmara Universities in Istanbul, Turkey. RESULTS: Using the EAT 40 cut-off score of 30 established by (16) 7.9% of subjects were classified as having abnormal eating attitudes and behaviours. This subgroup of subjects was then compared with the remainder on all the other measures. No group differences were found for any of the SES variables. However, both social and individual variables were found to distinguish between groups in the predicted directions. DISCUSSION: Abnormal eating attitudes and behaviours are now as common in Turkish students as they are in many other comparable western and, increasingly, non-western societies. In the current student sample these attitudes and behaviours were found to be related to social factors such as the perceived traditionality of parents as well as to individual risk factors such as negative perfectionism.

Adolescent↗

[Structural bases of individual variability in the human brain].

The paper shows considerable differences in the cytoarchitectonical organization of cortical fields 44, 45, and 4, 6 in the brain of different persons. The profile fields of pyramidal neurons in layers III and V substantially differ from each other for the cortical fields under investigation. The specific features of the total fractions of neurons and glia in the cortical fields in different brains are outlined. The density of neuronal location is an important criterion for individual variability. The magnitude of individual variability manifests itself the right and left hemispheres by different ways.

Adult↗

Inter-individual variability in the oxidation of 1,2-dibromoethane: use of heterologously expressed human cytochrome P450 and human liver microsomes.

1,2-Dibromoethane (1,2-DBE) is mainly used as an additive in leaded gasoline and as a soil fumigant and it is a suspected carcinogen in humans. In this study, the oxidative bioactivation of 1,2-DBE to 2-bromoacetaldehyde (2-BA) was studied using heterologously expressed human cytochrome P450 (P450) isoenzymes and human liver microsomes. Out of ten heterologously expressed human P450 isoenzymes (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1, CYP2C8, CYP2C9, CYP2C18, CYP3A4 and CYP3A5), only human CYP2A6, CYP2B6 and CYP2E1 metabolized 1,2-DBE, albeit with strongly differing catalytic efficiencies. The apparent Km and Vmax values were 3.3 mM and 0.17 pmol/min per pmol P450 for CYP2A6, 9.7 mM and 3.18 pmol/min per pmol P450 for CYP2B6 and 42 microM and 1.3 pmol/min per pmol P450 for CYP2E1, respectively. In all of 21 human liver samples studied, 1,2-DBE was oxidized with activities ranging from 22.2 to 1027.6 pmol/min per mg protein, thus showing a 46-fold inter-individual variability. The kinetics of the oxidative metabolism of 1,2-DBE to 2-BA in human liver microsomes were linear, indicating the involvement of primarily one single P450 isoenzyme. There was a tendency towards a positive correlation between the oxidative metabolism of 1,2-DBE in the human liver microsomes and the 6-hydroxylation of chlorzoxazone, a selective substrate for CYP2E1. Furthermore, the oxidative metabolism of 1,2-DBE was inhibited by the specific CYP2E1 inhibitors disulfiram (DS) and diethyldithiocarbamate (DDC). In contrast, a poor correlation was found between the immunochemically quantified amount of CYP2E1 and the microsomal chlorzoxazone 6-hydroxylation or the 1,2-DBE oxidation. The results indicate that CYP2E1 is probably the major P450 isoenzyme involved in the oxidative hepatic metabolism of 1,2-DBE in humans. The inter-individual variability in the oxidative bioactivation of 1,2-DBE in humans, largely due to inter-individual variability in the catalytic activity of hepatic CYP2E1, may have important consequences for the risk assessment for human exposure to 1,2-DBE.

Acetaldehyde↗

Inter-individual variability in the torque-related patterns of responses for mechanomyographic amplitude and mean power frequency.

The purpose of this study was to examine the inter-individual variability for the patterns of responses for mechanomyographic (MMG) amplitude and mean power frequency (MPF) versus isometric torque in lower-strength (LS) and higher-strength (HS) individuals. Twelve participants (mean +/- S.D. age = 25 + 4 years) performed two isometric maximal voluntary contractions (MVCs) before and after completing nine submaximal step muscle actions (15%, 25%, 35%, 45%, 55%, 65%, 75%, 85%, and 95% MVC) of the right leg extensors. MMG signals were recorded from the vastus lateralis muscle, and MMG amplitude and MPF values were computed for each corresponding percentage of the MVC. Polynomial regression analyses indicated that the composite MMG amplitude versus isometric torque relationship was best fit with a linear model (r(2) = 0.980) for the LS group and a cubic model (r(2) = 0.994) for the HS group. The composite MMG MPF versus isometric torque relationships were best fit with linear models for both the LS (r(2) = 0.529) and HS (r(2)=0.591) groups. However, only 66% of the individuals exhibited the same linear MMG amplitude patterns as the composite relationship for the LS group, whereas only 33% of the individual relationships were cubic for the HS group. Only one subject exhibited a positive linear (r(2) = 0.681) relationship for the MMG(MPF) versus isometric torque relationship for either the LS or HS groups. These findings suggested that strength differences do not affect the patterns of responses for MMG amplitude or MPF. The lack of consistency between the individual and composite patterns of responses suggested some degree of inter-individual variability. Therefore, future studies should examine the individual patterns of response to draw conclusions about motor control strategies.

Acceleration↗

Comparative analysis of in vitro and in vivo pharmacokinetic parameters related to individual variability of GTS-21 in canine.

To clarify the cause of the canine individual variability in plasma concentration after oral administration of GTS-21, we evaluated in vitro the metabolism to 4-OH-GTS-21 in liver microsomes of the same individuals from in vivo pharmacokinetic study. First, we applied to the Michaelis-Menten kinetic parameters to a dispersion model, and compared hepatic availability (F(H)) and hepatic clearance (CL(H)) values from in vitro with bioavailability (F), hepatic plasma flow (Q(PH)), and plasma clearance (CL(P)) values from in vivo. The ratios of CL(H) to Q(PH) were ranged 0.74 to 0.94, suggesting that GTS-21 is a hepatic plasma flow-limiting drug. A significant correlation of F(H) and F in the four dogs (r=0.995, p=0.005) indicates that the variability is predominantly caused by GTS-21 O4-demethylase activity. Second, we specified the cytochrome P450 (CYP) enzymes that are involved with the metabolism by chemical inhibition. alpha-Naphthoflavone, furafylline, quinidine, quinine, and troleandomycin significantly inhibited GTS-21 O4-demethylase activity. Thus CYP1A, CYP2D15, and CYP3A12 were involved with O4-demethylation. The variability in control activity decreased on addition of alpha-naphthoflavone and furafylline. Third, we quantified the contents of CYP1A and CYP3A12 by enzyme-linked immunosorbent assay. The content of CYP1A was consistent with GTS-21 O4-demethylase activity. We concluded that canine liver CYP1A causes the individual variability in GTS-21 plasma concentration after oral administration.

Journal Article↗

Intra-individual variability in nighttime urine production and functional bladder capacity estimated by home recordings in patients with nocturnal enuresis.

PURPOSE: We evaluated the intra-individual variability and reproducibility of nighttime urine production on wet nights and functional bladder capacity estimated by long-term home recordings of monosymptomatic nocturnal enuresis. In particular, the intention was to evaluate the validity of 1 versus 2 weeks of recording when estimating urine volume on wet nights and 1 versus 2 weekends of recording when estimating functional bladder capacity. MATERIALS AND METHODS: We analyzed 120, 2-week home recordings of nighttime urine volume from patients with monosymptomatic nocturnal enuresis 6 to 16 years old (mean age 9.1) with at least 3 wet nights per week. Most patients were nonresponders or partial responders to desmopressin. Nighttime urine volume was estimated by weighing diapers before and after sleep, and measuring morning urine volume. Of the home recordings 62 included frequency volume charts for 2 weekends, which were evaluated for functional bladder capacity defined as the largest voided volume observed. RESULTS: No significant overall week-to-week differences were observed in average urine volume on wet nights and functional bladder capacity. There was a large intra-individual variability in all measured variables, which was most pronounced for functional bladder capacity and least pronounced for urine volume on wet nights. With regard to repeatability, the limits of agreement of urine volume on wet nights were -32% and 36% (95% confidence interval) as opposed to -54% and 48% for functional bladder capacity. CONCLUSIONS: In this study intra-individual week-to-week estimates of average urine volume on wet nights demonstrated acceptable variability and repeatability in contrast to functional bladder capacity. A reliable estimate of urine volume on wet nights could be obtained by 7 nights of home recording, whereas 4 days of daytime recording were necessary when estimating functional bladder capacity. Similar studies of patients who respond to desmopressin are needed.

Adolescent↗

Estimating digestion rate and the problem of individual variability, exemplified by a scyphozoan jellyfish.

Short-term (h) and long-term (days) individual variability and the effects of momentary change in feeding intensity on digestion time were studied in the scyphomedusa Aurelia aurita as a basis for developing a method to experimentally measure the digestion rate with a high precision. Ten individual medusae showed only small, non-significant differences in average digestion time (range, 2.1-2.5 h at 10 degrees C) over a 9-day experiment, whereas variability within and between days and between individuals at a given occasion was high. When medusae were manually kept at a constant feeding intensity, stomach fullness showed high variability both between individuals and within an individual over time. With a feeding intensity of, respectively, 1, 2, 4 and 8 prey h(-1) over a 5-h experimental period, stomach fullness of most individuals corresponded to a theoretical digestion time of 1-3 h, whereas single meals of the same size usually gave somewhat higher digestion time. Medusae subject to a switching from a low to a high feeding intensity tended to increase the variability, but most individuals showed a digestion time of 1-3 h. An opposite switching tended to increase the digestion time and its variability. It is concluded that the digestion time of A. aurita is randomly variable over time within given limits for a given food and environmental condition. This variability is non-synchronised in the population, causing high variability between individuals, and changes in the feeding intensity cause additional variability. However, the average digestion time of A. aurita in a physically and nutritionally stable environment is robust, and changes in the feeding intensity give predictable effects. The use of field collected data on stomach contents and laboratory determined digestion times is therefore an attractive method to calculate predation rate, but the inherent high variability in digestion time must be taken into consideration when designing the digestion experiments. Based on these findings a simple experimental method to determine the digestion time of aquatic animals is outlined and evaluated. The digestion time is simply given as the ratio between number of prey in stomach and total number of prey eaten, times the incubation time, assuming that the feeding intensity is constant.

Journal Article↗

Individual variability in symptoms, ischemic threshold and cardiovascular efficiency during exercise testing in patients with effort angina.

This study assessed both group and individual variability of ECG exercise stress test in patients with effort angina. Forty-five untreated patients with typical effort angina, without evidence of spontaneous angina, with a positive exercise stress test (ST depression greater than 0.2 mV) and angiographically documented coronary artery disease were studied. Four multistage exercise stress tests were performed, two in the morning and two in the afternoon, on two consecutive days. Forty-four patients completed the protocol for a total of 176 exercise stress tests. For each exercise stress test the following parameters were analyzed: time to 0.15 mV ST segment depression (time to ischemia); rate-pressure product at ischemia (ischemic threshold); slope and intercept of the linear regression between rate-pressure product and time of exercise. Silent effort ischemia was largely prevalent: 21 patients (48%) experienced chest pain in all four tests, but only seven showed a consistent time relationship between pain and ECG changes. Symptomatic patients did not appear different from the asymptomatic ones in terms of clinical and angiographic data. When group data were analyzed for each parameter the four exercise stress tests appeared reproducible. In contrast, when individual variability of each parameter was computed as the percentage difference between range (maximum--minimum) and maximal value obtained in the series of four exercise stress tests, a large variability was detected. Variability of time to ischemia, was 27.2 +/- 17.4%. This resulted from a random combination of variability in ischemic threshold (19.1 +/- 9.2%), slope (28.4 +/- 12.8%) and intercept (22.7 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Inter-individual variability of gene expression detected by biochips].

BACKGROUND: For gene expression profiling in leukemia patients we use array technologies in our laboratory. The assays are based on the comparison of patient and control expression profiles. Expression profile of the control sample should be representative but there is a problem of inter-individual variability in population, because also healthy persons display differences in gene transcription activity. Aim of the study was to characterize expression profiles of controls and to determine variability rate. METHODS AND RESULTS: The control group comprised 15 "healthy" persons (9 peripheral bloods, 2 bone marrows, 4 cord bloods) from various age categories (0 to 56 years). Expression profiles were detected using Atlas Human Cancer cDNA Expression Arrays (Clontech) with 588 gene probes. Total RNAs were isolated from leukocytes and were reverse transcribed into cDNA. Out of 588 tested genes on average 24% were detected. Inter-individual variability of gene expression profiles of leukocytes from the same tissue did not exceed 25%. Majority of the genes, with significant changes in leukemia patients, was expressed at similar level in the control group, with the exception of bone marrow and cord blood samples that demonstrated higher expression of PCNA, MMP8, MMP9 genes. In bone marrow high PCNA expression could result from active cell proliferation in this tissue. Strong expressions of MMP8 and MMP9 might be associated with the presence of cell precursors because there were not detected in peripheral blood leukocytes. Expression of some genes was tissue specific or followed "ontogenetic" trend. CONCLUSIONS: The inter-individual expression variability has to be taken into account in expression comparative analyses. In order to minimize the influence of existing variability we use mixed control samples and statistical data processing.

Adult↗