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Neuropsychological and behavioural correlates of CSF biomarkers in dementia.

To improve clinical, neuropsychological and behavioural characterisation of the cerebrospinal fluid (CSF) biomarkers beta-amyloid((1-42)) protein (Abeta42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was set up. Patients with probable Alzheimer's disease (AD) (n=201), AD with cerebrovascular disease (CVD) (AD+CVD) (n=33), frontotemporal dementia (FTD) (n=27), dementia with Lewy bodies (DLB) (n=22) and healthy controls (n=148) were included. All patients underwent neuropsychological examination and behavioural assessment by means of a battery of behavioural assessment scales. CSF was obtained by lumbar puncture and levels of Abeta42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF Abeta42 levels and aggressiveness (Spearman: r=-0.223; p=0.002) and positive correlations with age at inclusion (r=0.195; p=0.006), age at onset (r=0.205; p=0.003) and MMSE scores (r=0.198; p=0.005) were found in AD. In AD+CVD, CSF Abeta42 levels were correlated with MMSE (r=0.482; p=0.006), Hierarchic Dementia Scale (r=0.503; p=0.017) and Boston Naming Test (r=0.516; p=0.012) scores. In controls, age was positively correlated with CSF tau (r=0.465; p<0.001) and P-tau181 levels (r=0.312; p<0.001). CSF tau and P-tau181 levels correlated significantly in all groups, whereas CSF Abeta42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF Abeta42 levels and aggressiveness were found in AD patients. CSF Abeta42 seems to be a stage marker for AD (+/-CVD) given the positive correlations with neuropsychological test results suggesting that CSF Abeta42 might be of help for monitoring disease progression. Different correlations between age and CSF biomarker levels were obtained in healthy controls compared to AD patients, indicating that AD-induced pathophysiological processes change age-dependent regulation of CSF biomarker levels.

Adolescent↗

Long-range temporal correlations in electroencephalographic oscillations: Relation to topography, frequency band, age and gender.

Presence of long-range temporal correlations in neuronal oscillations is thought to be beneficial for a reliable transfer of information in neuronal networks. In the present study long-range temporal correlations in electroencephalographic (EEG) neuronal oscillations were characterized with respect to their topography, frequency-band specificity (alpha and beta oscillations), gender and age. EEG was recorded in 91 normal subjects (age 20-65 years) in a resting condition. The amplitude of ongoing alpha and beta oscillations was extracted with band-pass filtering and Hilbert transform, and long-range temporal correlations were analyzed with detrended fluctuation analysis. The topography of long-range temporal correlations was comparable for alpha and beta oscillations, showing largest scaling exponents in the occipital and parietal areas. This topography was partially similar to that of the power distribution and a weak positive correlation was observed between long-range temporal correlations and power of neuronal oscillations. Long-range temporal correlations were stronger in alpha than beta oscillations, but only in a few electrode locations in the left hemisphere. In both frequency bands long-range temporal correlations were stronger in males than in females and were largely unaffected by the age of the subjects. It is hypothesized that the idling state of the occipital areas in the closed-eyes condition may explain both large power values and pronounced long-range temporal correlations in this region.

Action Potentials↗

Long-range temporal correlations in the spontaneous spiking of neurons in the hippocampal-amygdala complex of humans.

The spontaneous or background discharge patterns of in vivo single neuron is mostly considered as neuronal noise, which is assumed to be devoid of any correlation between successive inter-spike-intervals (ISI). Such random fluctuations are modeled only statistically by stochastic point process, lacking any temporal correlation. In this study, we have investigated the nature of spontaneous irregular fluctuations of single neurons from human hippocampus-amygdala complex by three different methods: (i) detrended fluctuation analysis (DFA), (ii) multiscale entropy (MSE), (iii) rate estimate convergence. Both the DFA and MSE analysis showed the presence of long-range power-law correlation over time in the ISI sequences. Moreover, we observed that the individual spike trains presented non-random structure on longer time-scales and showed slow convergence of rate estimates with increasing counting time. This power-law correlation and the slow convergence of statistical moments were eliminated by randomly shuffling the ISIs even though the distributions of ISIs were preserved. Thus the power-law relationship arose from long-term correlations among ISIs that were destroyed by shuffling the data. Further, we found that neurons which showed long-range correlations also showed statistically significant correlated firing as measured by correlation coefficient or mutual information function. The presence of long-range correlations indicates the history-effect or memory in the firing pattern by the associative formation of a neuronal assembly.

Action Potentials↗

Multiple correlations and Bonferroni's correction.

Correlation coefficients between biological measurements and clinical scales are often calculated in psychiatric research. Calculating numerous correlations increases the risk of a type I error, i.e., to erroneously conclude the presence of a significant correlation. To avoid this, the level of statistical significance of correlation coefficients should be adjusted. Threshold levels of significance for correlation coefficients were adjusted for multiple comparisons in a set of k correlation coefficients (k = 1, 5, 10, 20, 50, 100) by Bonferroni's correction. Significant correlation coefficients were then calculated according to sample size. The change in the threshold values of significance is larger when the number of correlations goes from 1 to 5 than when it goes from 50 to 100. A correlation coefficient, statistically significant at 5% when calculated alone, can be under the threshold level of significance when calculated even among a few other coefficients. Focusing on the most relevant variables or the use of multivariate statistics is advocated.

Data Interpretation, Statistical↗

[Girls are more successful than boys at the university. Gender group differences in models integrating motivational and aggressive components correlated with Test-Anxiety].

It is surprising to note the evolution of success rates in Belgian universities especially in the first Year. Men are less successful than women and the differences are escalating in an alarming way. Dropouts take the same direction and women now represent a majority of the students at the university. In a previous study, we assessed 616 students in the first Year at the university of Liège with Vasev, the English name of which was TASTE, a self report questionnaire constituted of 4 factors: anxiety, self confidence, procrastination and performance value; anxiety particularly concerned somatic expression of students before and during test evaluations; self confidence was a cognitive component close to self efficacy; procrastination was the behavioral component characterizing avoidance when students are confronted with the risk of failure; performance value referred to intrinsic and extrinsic motivations. French validation of TASTE led to an abbreviated version of 50 items (THEE) consisting of 5 factors, the four of TASTE and an additional one, very consistent, at first called depression because of its correlations with this dimension, then called sense of competence on account of its semantic content. Self-competence has been described in the literature of Achievement Motivation and corresponded to expectancy and ability beliefs in performance process which was also relevant to self-efficacy except the particularity of comparison with others, which was not included in the last construct. Self-competence has been considered as an important part of the Worry component of test anxiety. Some Authors didn't hesitate to view causality flowing from self-competence to test anxiety and have conceptualized the latter as a failure of the self where one's sense of competence has been undermined as a result of experienced failure. In our study, only that factor was equally scored in women and men whereas it was scored higher in failed students. In other respects anxiety and performance value were scored higher in women, self-confidence and procrastination higher in men. Because TASTE didn't discriminate the different components of motivation (performance value referred to intrinsic and extrinsic motivations without precise distinction) we decided to use the MPS (Multidimensional Perfectionism Scale) which gave the opportunity to distinguish SOP (Self Oriented Perfectionism) ie, the self-imposed unrealistic standards with inability to accept faults in order to know and master a subject, that corresponded to intrinsic motivation; SPP (Socially Prescribed Perfectionism) ie, the exaggerated expectancies of others which are subjectively believed as imposed and uncontrollable leading to anxiety, feelings of failure or helplessness, that corresponded to extrinsic motivation; POO (Perfectionism Oriented to Others) ie, the unrealistic demands expected from significant others, which especially characterized males. We assumed that women attached more importance to succeed and submitted more to society exigencies. That way extrinsic and intrinsic motivations were probably more combined unlike men who, dreading a loss of self esteem, tried to avoid failure responsibility in using self handicapping or aggressive behaviours, so separating motivation in an extrinsic part turned to performance value and an intrinsic one more concerned by self confidence and sense of competence with the result that the motivational balance was surely disrupted in case of high competition leading to failure or avoidance. In another previous study we established a structural model illustrating, according to gender, correlations between anxiety, sense of incompetence, self-oriented perfectionism and socially prescribed perfectionism. Self-oriented perfectionism was less correlated to socially prescribed perfectionism in boys than in girls; furthermore especially by those who had never failed, it was negatively correlated to sense of incompetence, thus leading to lower scores of anxiety while in girls, by contrast, such a correlation didn't exist, thus involving higher anxiety. That way, on the one hand, intrinsic and extrinsic motivations by female students complementarily operated on the sense of incompetence and consequently on anxiety, the emotional component of test anxiety; on the other hand, by male students, intrinsic motivation had a negative correlation with the sense of incompetence and a lower correlation with extrinsic motivation, thereby shedding some light on the problem of anxiety level differences according to gender. More, that observation corresponded well to the model of self-worth where test anxiety was understood as a manifestation of perceived incompetence and as a defensive way to ward off negative self-evaluation; that model suited particularly well to boys and explained their attempts to maintain self-worth when risking academic failure. The present research assumes that independence or combination of motivation components is also correlated to different expressions of aggressiveness: hostility corresponding to threat and characterizing more girls while physical aggression is corresponding to personal challenge, a more masculine attribution. If fighting against the sense of incompetence actually characterizes men and consequently shows too the competitive aspects of performance strong enough to mobilize intrinsic motivation, what would be expected regarding the notion of threat suspected to be predominant in girls? The idea of using a questionnaire discriminating the specific dimensions of aggressiveness in fact the Aggression Questionnaire should meet the following purposes: At first establish a French version of that aggression questionnaire, perform the factorial analyses and internal consistency, compare them with other previous samples, then differentiate gender in general and in failure versus success situations. Finally include the different components of aggressiveness in the first described model and build a new one liable to define in boys the explicit pathways between test anxiety, perfectionism and aggressiveness. Statistical analyses have confirmed, in a 3 factor solution, the presence of emotional (anger), cognitive (hostility) and behavioural (physical aggression) components. Internal consistency is satisfactory. It is demonstrated that physical aggression characterizes boys (F=12.04, p=0.0001) while hostility (F=5.22, p=0.0015) and anger (F=0.49, p=0.0001) characterizes girls; furthermore it is noted that physical aggression characterizes more failed students (F=13.43, p=0.0003). Four models (see figures 2, 3, 4, 5) have been established, at first focused on the distinction of correlations between motivation and cognitive and emotional components on the samples of boys (n=268) and girls (348), then developed on the samples of successful students, male (n=193) and female (n=271). They describe the differentiated action of intrinsic and extrinsic motivations on the different components of aggressiveness and test-anxiety according to gender and without experience of failure. The dynamic process of the organizational factors is different according to gender and psychopathology resulting from the combinations of behaviors, cognitions and emotions would be assumed, prioritizing physical aggression and psychopathy by boys, anxiety and depression by girls. Anyway more explanation about the evolution of success rates of boys and girls in Belgian universities is proposed.

Adult↗

Correlation of plasma homocysteine and mitochondrial DNA content in peripheral blood in healthy women.

Hyperhomocysteinemia is an independent risk factor of cardiovascular disease and associated with insulin resistance, although their causal relationship remains unclear. A previous report has shown that high concentration of homocysteine damages mitochondrial gene expression, function and structure. As we found recently, the mitochondrial DNA (mtDNA) contents are inversely correlated with insulin resistance parameters. Thus there is possibility that plasma total homocysteine (tHcy) level is somewhat correlated with mtDNA content. Sixty healthy women (mean age 40.3+/-20.9 yr, range 18-78 yr) were recruited to investigate the correlation of plasma tHcy level and mtDNA content in peripheral blood. A significant negative correlation was found between plasma tHcy levels and mtDNA content (r=-0.507, P<0.01). Plasma tHcy and mtDNA content have an independent effect on each other and on insulin resistance (HOMA-insulin resistance (IR) score) respectively in multiple regression model. Plasma tHcy showed positive correlations with age (r=0.407), W/H ratio (r=0.370), total cholesterol (r=0.338), LDL-cholesterol (r=0.317) and insulin resistance (HOMA-IR score) (r=0.261); and a negative correlation with folate (r=-0.273). MtDNA content showed negative correlations with age (r=-0.407), BMI (r=-0.440), W/H ratio (r=-0.659), SBP (r=-0.350), total cholesterol (r=-0.340), triglyceride (r=-0.376), LDL-cholesterol (r=-0.349), fasting plasma insulin (r=-0.483), and insulin resistance (HOMA-IR score) (r=-0.423); and a positive correlation with folate (r=0.299). In this study, there was a significant inverse correlation between plasma tHcy level and mtDNA content. Further study will be warranted to elucidate the mechanism by which two factors are associated.

Adolescent↗

Effects of correlated and synchronized stochastic inputs to leaky integrator neuronal model.

We present an analysis of neuronal model behaviour with correlated synaptic inputs including the cases that correlated inputs are equivalent to exactly synchronized inputs and correlated inputs are not equivalent to exactly synchronized inputs. For the former case, it is found that the fully (synaptically) correlated inputs assumption (see Section 1 for definition), which is used in most, if not all, theoretical and experimental work in the past few years, results in a waste of resources and might be an unrealistic assumption; with an exactly balanced excitatory and inhibitory, and synaptically correlated input, the integrate-and-fire model simply behaves as a synchrony detector in certain parameter regions; the well-known diffusion model, upon which most theoretical work is based, fails to approximate the model with synaptically correlated Poisson inputs. A novel way to approximate synaptically correlated Poisson inputs is then presented;an optimization principle on neuronal models with partially (synaptically) correlated inputs is proposed, which enables us to predict microscopic structures in neuronal systems. For the latter case,with tightly synchronized inputs (see Section 1 for definition), the model behaviour depends on its integration time of input signals and could exhibit bursting discharge.for loosely synchronized inputs, we found that correlated inputs are equivalent to the post-spike voltage reset mechanism proposed in the literature.

Action Potentials↗

Correlation between cerebral blood flow and items of the Hamilton Rating Scale for Depression in antidepressant-naive patients.

BACKGROUND: The purpose of this study was to correlate the basal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) with the score for each of the 21 questions in the Hamilton Rating Scale for Depression (HRSD), in order to determine the cerebral regions associated with each item. METHODS: Fourteen antidepressant-naive patients with unipolar depression (DSM-IV criteria for MDD) participated in this study with a HRSD score of >/=20 points. CBF images obtained by SPECT were analyzed by SPM99 software. The significant correlation threshold for a priori regions (frontocortical and limbic regions) was a Z value of at least 2.25 and clusters formed by more than 10 voxels. RESULTS: Items 1, 6, 11 and 20 were positively correlated with right medial frontal gyrus; item 7 was negatively correlated with bilateral medial frontal gyrus. Items 2 and 10 were positively correlated with right anterior and medial cingulate, respectively. Item 5 was negatively correlated with the left amygdala. Item 9 was negatively correlated with bilateral insula, and item 16 with right insula. Items 12 and 14 were positively correlated with right and left precentral frontal gyrus, respectively. LIMITATIONS: The small sample size and only out-patients included in the study. CONCLUSIONS: The frontal cortex plays an important role in the expression of MDD symptoms. Not all the symptoms evaluated correlated with one single structure, which may explain the diverse results reported in the literature. These preliminary results support the necessity of further analyses by symptoms that could provide more specific information on the pathophysiology of MDD.

Adult↗

The relationship between rhythmic activities during a mental task and sleep spindles: a correlative analysis.

In a previous study, we suggested that the characteristics of theta, alpha, and beta rhythms during a mental task were similar to those during sleep. Building upon the previous data, correlations between rhythmic activities during a mental task and during sleep were investigated in the present study. Patterns of correlation and no correlation between rhythmic activities during the mental task were similar to those during sleep for subjects with and without frontal midline theta (Fmtheta) activity. In the Fmtheta group, there were no correlations between rhythmic activities in the two situations, while in the non-Fmtheta subjects, theta and alpha rhythms showed a positive correlation with one another, and theta and beta rhythms correlated negatively during sleep. In both groups, there were many correlations between rhythmic activities during the mental task and those in Sleep Stage 2, while there were few correlations between rhythmic activities during the mental task and those in other sleep stages. These results suggest that the mechanism generating rhythmic activities during the appearance of rhythmic activities induced by a mental task may be closely related to those of rhythmic activities during sleep, and that the membrane potentials in reticular thalamic (RE) neurons during the appearance of rhythmic activities induced by a mental task may be nearly equivalent to that in Sleep Stage 2, and that the correlation pattern between the rhythmic activities in each group may be well explained by the appearance pattern of each rhythm in the previous report.

Adult↗

Correlation between rCBF and speech perception in cochlear implant users.

OBJECTIVE: Although cochlear implants (CIs) have provided the opportunity for bilaterally deaf individuals to recover their hearing abilities, the speech perception performances of the CI users varies considerably. To elucidate the cortical mechanisms of processing speech signals coded by CIs, we evaluated the correlation between the brain activity during speech activation and speech perception in CI users by PET. METHODS: Fourteen postlingually deaf CI users were examined. CI used in the patients was a 22-channel system and its speech-coding strategy was the Nucleus spectral peak (SPEAK) strategy. To evaluate the speech perception performances, we examined vowel perception, consonant perception and speech tracking performances in the Japanese language. Regional cerebral blood flow (rCBF) was measured during no sound stimulation and speech sound stimulation. PET data of the silent condition was subtracted from that of speech stimulation to determine changes in rCBF. In the search for changes in rCBF in the areas for auditory processing, three regions of interest (ROI) were selected; primary auditory area, auditory association area and Broca's area. The correlation between the rCBF changes in the ROIs and the speech perception performances was analyzed using Pearson's correlation coefficient. RESULTS: The patient's speech perception performances ranged widely. Although there were no significant correlations between the speech perception and the rCBF increases in the primary auditory area and Broca's area, there were positive correlations in the auditory association area. In the left auditory association area, the correlation coefficient of the vowel perception performance was 0.546 (P <0.05) and that of the speech-tracking test was 0.657 (P < 0.05). Regarding the consonant perception performance, the correlation coefficient was 0.743 (P < 0.01). There was a positive correlation only between the consonant perception performance and the rCBF increase (R = 0.576, P < 0.05) in the right auditory association area. These correlations are stronger in the left hemisphere than in the right hemisphere. CONCLUSIONS: It is suggested that the improvement of the auditory processing of speech in CI users with SPEAK strategy is accompanied by the recruitment of more neurons in the auditory association areas. The adult auditory cortices may still have plasticity or

Adult↗

Waking EEG power spectra in the rat: correlations with training performance.

Adult rats chronically implanted with supradural electrodes were telemetrically EEG recorded during a baseline session, a training session for a two-way active avoidance task, and a retention session. Rats were assigned to a fast learning (FL), slow learning (SL) and non learning (NL) group if they achieved criterion during the training session, the retention session, or in neither session. High-resolution EEG analyses indicated that intergroup differences were present in the low frequency range of waking baseline power spectra. Moreover, baseline delta emissions directly correlated with freezings, and inversely correlated with avoidances, while emissions at 7-10 Hz directly correlated with avoidances and inversely correlated with freezings. Interestingly, during the first training period, waking delta emission selectively increased in FL rats in concomitance with a marked performance improvement; instead, SL and NL rats displayed increments at 7-9 Hz. In addition, freezings scored during the first two training periods directly correlated with post-training waking emission at 2 Hz, and inversely correlated with emission at 7-10 Hz. Conversely, escapes and avoidances directly correlated with waking emission at 7-10 Hz. The data indicate that (i) waking baseline power spectra differ among behavioral groups, and correlate with behavioral performance the following day; (ii) selective modifications of waking power spectra occur in each behavioral group during training; and (iii) behavioral responses during training correlate with post-training waking power spectra. Notably, the delta increment selectively occurring in training FL rats is assumed to reflect online memory processing leading to better performance. The latter observation supports the primary involvement of delta waves in learning.

Animals↗

Measurements of lumbopelvic lordosis using the pelvic radius technique as it correlates with sagittal spinal balance and sacral translation.

BACKGROUND CONTEXT: Maintenance of normal lumbar lordosis is important in the treatment of spinal disorders. Many attempts have been made to quantify normal sagittal spinal alignment and lordosis using a C7 plumb line and segmental angulations of the spinal vertebrae. Little attention has been given to pelvic compensation as it correlates to lumbar lordosis and overall sagittal spinal alignment. Better methods of measuring lordosis, which correlate with sagittal spinal balance and pelvic compensation, are needed in treating patients with spinal disorders. PURPOSE: To determine the correlation between lumbopelvic lordosis, pelvic rotation and sagittal spinal balance and standardize a method for measuring lumbopelvic lordosis, sacral translation, and sagittal spinal alignment. STUDY DESIGN: Sagittal alignments using the C7 plumb line, Cobb angles, sacral plumb line and the pelvic radius (PR) technique were used to measure standing 36-inch lateral radiographs of patients with various spinal disorders. PATIENT SAMPLE: A review of the records identified 62 patients with various spinal pathologies presenting to the (RGW) spine clinic that had standing lateral spine radiographs. Only radiographs that allowed positive identification of the C7 vertebral body, the entire thoracolumbar spine, the sacrum and both femoral heads were studied. These criteria allowed inclusion of 28 subjects in this study. The final population had 12 women and 16 men with an average age of 52 years (SD, 16.6 years; range, 20 to 84 years). OUTCOME MEASURES: No outcomes measures were used in this study. METHODS: Measurements for sagittal spinal balance and lumbopelvic lordosis were made on 36-inch standing lateral radiographs of adult patients. Measurements included the C7 plumb line, segmental angulations of spinal vertebrae (Cobb angles), sacral translation and the PR technique for lumbopelvic lordosis. Data were analyzed for significant correlation between lumbopelvic lordosis, sagittal spinal balance, sacral translation and total segmental lumbar lordosis using the Cobb method. RESULTS: Our population averaged 50 degrees of total segmental lumbar lordosis from L1 to S1 (SD, 14.3; maximum, 89.5; minimum, 17.9). Nearly 75% of total segmental lumbar lordosis measured from L1 to S1 can be accounted for through the L4 to S1 superior end plates and 47% through L5 to S1 superior end plates in our population. Total segmental lumbar lordosis correlated with total thoracic kyphosis (r=0.45, p=.008). Total segmental lumbar lordosis measured by the Cobb method significantly correlated with sagittal spinal balance (r=-0.35, p=.022) and sacral translation (r=0.41, p=.016). Measurements for lumbopelvic lordosis significantly correlated with sagittal spinal balance (r=-0.33, p=.042), sacral translation (r=-0.70, p=.00002) and total segmental lumbar lordosis (r=0.82, p<.000001). Measurements for sacral translation and sagittal spinal balance also correlated significantly (r=0.35, p=.034). CONCLUSIONS: Sacral translation, the C7 plumb line and lumbopelvic lordosis are useful measures for sagittal spinal balance. Lumbopelvic lordosis and sacral translation can be correlated to the sagittal spinal balance. Understanding these measurements and the range of lumbopelvic compensation can be extremely helpful in treating patients with spinal pathology and in avoidance of flatback deformity. Application of these measures would be especially helpful in the treatment of patients with spinal fusion, degenerative spondylosis, disc disease, fractures, and in the prevention of sagittal malalignment.

Adult↗

Sample-sample and wavenumber-wavenumber two-dimensional correlation analyses of attenuated total reflection infrared spectra of polycondensation reaction of bis(hydroxyethyl terephthalate).

Polycondensation reaction of bis(hydroxyethylterephthalate) was monitored in situ by attenuated total reflection (ATR)/infrared (IR) spectroscopy. The obtained spectra are analyzed by means of generalized two-dimensional (2D) sample-sample and wavenumber-wavenumber correlation spectroscopies. The sample-sample correlation analysis reveals the correlations among the concentration features of the components, and the wavenumber-wavenumber correlation analysis elucidates the relations among the spectral features. Before the experimental data are analyzed by the 2D correlation spectroscopies, a synthetic two-component spectral model composed of the first and the last experimental spectra, is examined. The results of an analysis of the real data are related to those obtained from the synthetic data. It is found that the sample-sample correlation analysis of the IR data of polycondensation explains the concentration variance in the system and classifies two groups of the samples. The wavenumber-wavenumber correlations are derived upon the results of the sample-sample correlations and explained in terms of the spectral variations of three components. The convolute patterns in both types of correlations are attributed to the weak presence of ethylene glycol.

Journal Article↗

Genetic and phenotypic correlations among size-related traits, and heritability variation between body parts in Drosophila buzzatii.

Recent studies have shown that body size is a heritable trait phenotypically correlated with several fitness components in wild populations of the cactophilic fly Drosophila buzzatii. To obtain further information on size-related variation, heritabilities as well as genetic and phenotypic correlations among size-related traits of several body parts (head, thorax and wings) were estimated. The study was carried out on an Argentinean natural population in which size-related selection was previously detected. The genetic parameters were estimated using offspring-parent regressions (105 families) in the laboratory G2 generation of a sample of wild flies. The traits were also scored in Wild-Caught Flies (WCF). Laboratory-Reared Flies (LRF) were larger and less variable than WCF. Although heritability estimates were significant for all traits, heritabilities were higher for thorax-wing traits than for head traits. Phenotypic and genetic correlations were all positive. The highest genetic correlations were found between traits which are both functionally and developmentally related. Genetic and phenotypic correlations estimated in the lab show similar correlation pattern (r = 0.49; P = 0.02, Mantel's test). However, phenotypic correlations were found to be typically larger in WCF than in LRF. The genetic correlation matrix estimated in the relatively homogeneous lab environment is not simply a constant multiplicative factor of the phenotypic correlation matrix estimated in WCF.

Animals↗

Preoperative proton-MR spectroscopy of gliomas--correlation with quantitative nuclear morphology in surgical specimen.

A comparison between data from proton-MR spectroscopy (1HMRS) and quantitative histomorphology of tumor cell nuclei in gliomas has not been reported up to now. Therefore, the question must be answered, if there are any significant correlations between histomorphology of gliomas and quantitative data from 1HMRS concerning tissue metabolites. Surgical glioma specimen (glioblastomas, astrocytomas, oligodendrogliomas) from 46 patients with tumor grades II-IV according to WHO have been evaluated by means of a digital image analysis system using Ki-67-immunostained paraffin sections. Nuclear density, Ki-67-proliferation index, nuclear area and shape variables (roundness factor, Fourier-amplitudes) have been determined from 200 randomly selected tumor cell nuclei in each tumor specimen. These data have been correlated with preoperative data from 1HMRS. A positive correlation between Fourier-amplitudes, choline peak and lipide peak was observed, as well as a negative correlation between these variables and the nuclear roundness factor. This result indicates higher choline and lipide peaks with increasing irregularity of nuclear outlines. Proliferation index Ki-67 was positively correlated with the lipide peak, nuclear density showed a positive correlation with the choline peak. Glioblastomas (n = 29) showed an additional positive correlation between mean nuclear size and total creatine. Anaplastic gliomas (n = 12) showed a positive correlation between lactate peak and the standard deviation of the nuclear roundness factor. Further multivariate analyses have shown, that for the present collective of 46 cases, histometric variables have a higher significance than spectroscopic data for the differentiation of the different tumor grades. These results verify a significant correlation between preoperative data from 1HMRS and histomorphology of tumor cell nuclei in gliomas, supporting the biological significance of both histomorphometry and 1HMRS for the evaluation of these tumors.

Brain Neoplasms↗

Genetic mechanisms of floral trait correlations in a natural population.

Genetic correlations among traits are important in evolution, as they can constrain evolutionary change or reflect past selection for combinations of traits. Constraints and integration depend on whether the correlations are caused by pleiotropy or linkage disequilibrium, but these genetic mechanisms underlying correlations remain largely unknown in natural populations. Quantitative trait locus (QTL) mapping studies do not adequately address the mechanisms of within-population genetic correlations because they rely on crosses between distinct species, inbred lines or selected lines (see ref. 5), and they cannot distinguish moderate linkage disequilibrium from pleiotropy because they commonly rely on only one or two episodes of recombination. Here I report that after nine generations of enforced random mating (nine episodes of recombination), correlations between six floral traits in wild radish plants are unchanged, showing that pleiotropy generates the correlations. There is no evidence for linkage disequilibrium despite previous correlational selection acting on one functionally integrated pair of traits. This study provides direct evidence of the genetic mechanisms underlying correlations between quantitative traits in a natural population and suggests that there may be constraints on the independent evolution of pairs of highly correlated traits.

Biological Evolution↗

The frequency and proliferative potential of megakaryocytic colony-forming cells (Meg-CFC) in cord blood, cytokine-mobilized peripheral blood and bone marrow, and their correlation with total CFC numbers: implications for the quantitation of Meg-CFC to predict platelet engraftment following cord blood transplantation.

CFC numbers have shown to correlate with success of engraftment and speed of neutrophil recovery following cord blood (CB) transplantation. To investigate whether the number of Meg-CFC in a CB stem cell preparation might correlate with time to platelet engraftment, we evaluated the frequency of Meg-CFC among all CFC types in 134 CB, 21 adult bone marrow (BM) and 52 cytokine-mobilized peripheral blood (PB) stem cell preparations. The correlation of Meg-CFC with the total number of CFC and mixed cell-CFC was also assessed. The frequency of Meg-CFC was highest in CB and correlated significantly with total CFC numbers (mean 20.8%, correlation coefficient (r) 0.84, P = 0.0001) compared with Meg-CFC from mobilized PB (mean 13.1%, r = 0.29, P = 0.07) and BM (mean 4%, r = 0. 39, P = 0.13). In addition, mixed-cell CFC numbers in CB were highly correlated with the total number of Meg-CFC (r = 0.7, P = 0.0001). No such correlations were found with mobilized PB or BM. We conclude that, based on the high degree of correlation between Meg-CFC and non-Meg-CFC numbers in CB, no additional information concerning time to platelet engraftment would be gained by routinely performing Meg-CFC assays in addition to non-Meg-CFC assays. The fact that CB Meg-CFC and mixed-cell CFC are strongly correlated suggests that CB Meg-CFC are more primitive than their counterparts in BM and PB and may reflect the number of stem cells in CB. Bone Marrow Transplantation (2000).

Adult↗

Correlational selection and the evolution of genomic architecture.

We review and discuss the importance of correlational selection (selection for optimal character combinations) in natural populations. If two or more traits subject to multivariate selection are heritable, correlational selection builds favourable genetic correlations through the formation of linkage disequilibrium at underlying loci governing the traits. However, linkage disequilibria built up by correlational selection are expected to decay rapidly (ie, within a few generations), unless correlational selection is strong and chronic. We argue that frequency-dependent biotic interactions that have 'Red Queen dynamics' (eg, host-parasite interactions, predator-prey relationships or intraspecific arms races) often fuel chronic correlational selection, which is strong enough to maintain adaptive genetic correlations of the kind we describe. We illustrate these processes and phenomena using empirical examples from various plant and animal systems, including our own recent work on the evolutionary dynamics of a heritable throat colour polymorphism in the side-blotched lizard Uta stansburiana. In particular, male and female colour morphs of side-blotched lizards cycle on five- and two-generation (year) timescales under the force of strong frequency-dependent selection. Each morph refines the other morph in a Red Queen dynamic. Strong correlational selection gradients among life history, immunological and morphological traits shape the genetic correlations of the side-blotched lizard polymorphism. We discuss the broader evolutionary consequences of the buildup of co-adapted trait complexes within species, such as the implications for speciation processes.

Animals↗