ChIP bias as a function of cross-linking time

The chromatin immunoprecipitation (ChIP) assay is widely used to capture interactions between chromatin and regulatory proteins in vivo. Formaldehyde cross-linking of DNA and proteins is a critical step required to trap their interactions inside the cells before immunoprecipitation and analysis. Yet insufficient attention has been given to variables that might give rise to artifacts in this procedure, such as the duration of cross-linking. We analyzed the dependence of the ChIP signal on the duration of formaldehyde cross-linking time for two proteins: DNA topoisomerase 1 (Top1) that is functionally associated with the double helix in vivo, especially with active chromatin, and green fluorescent protein (GFP) that has no known bona fide interactions with DNA. With short time of formaldehyde fixation, only Top1 immunoprecipation efficiently recovered DNA from active promoters, whereas prolonged fixation augmented non-specific recovery of GFP dramatizing the need to optimize ChIP protocols to minimize the time of cross-linking, especially for abundant nuclear proteins. Thus, ChIP is a powerful approach to study the localization of protein on the genome when care is taken to manage potential artifacts.     

Advanced modeling and identification techniques for metabolic processes

This paper will be devoted to demonstrating that a better understanding of complex metabolic processes requires a deep and reliable interpretation of much experimental data. Indeed this aim cannot be satisfied without the use of advanced modeling and identification techniques and their deep critical analysis. In fact, complete procedures should consider all the following steps: (1) definition of scopes, (2) prior information and hypotheses, (3) choice of experimental conditions, (4) derivation of possible classes of models, (5) parameter estimation, (6) errors evaluation, (7) validation and ordering of the identified models. This paper will mainly consider steps 4, 6, and 7 which are certainly the less assessed ones. However some real advances have been obtained in recent years which deserve to be more widely known and applied in practical problems. This paper will review such important contributions and will show, by means of applied examples, how they can be useful in avoiding ambiguities and incorrect interpretation of data and in evaluating the credibility of the inferred results.     

Signal attenuation as a function of integrator time constant and signal duration

In some laboratories, cyeblink electromyogram is rectified and smoothed before the analog signal is digitized. The relationship among the integrator time constant, the duration of the response, and the attenuation of the data was investigated by passing a number of signals at durations of 5, 10, 20, 50, and 100 ms into a contour-following integrator (Coulbourn model S76–01), which first rectifies and then smooths (integrates) the signal. Integrator time constants of 10, 42, 70, 144, and 300 ms were used. The output of the integrator was sampled (1,000 Hz) and stored on a Macintosh SE computer. The integrator attenuated the signal, and the amount of attenuation increased as the duration of the signal decreased and as the time constant of the integrator increased. For brief inputs, the integrator does not charge fully, so only the early portion of the charge limb is present, and this early portion is the steepest part of the charge limb. Therefore, the longer the time constant, the less likely that small or brief responses will be detected.     

Differential genetic etiology of reading component processes as a function of IQ

Results obtained from previous studies of word recognition, reading component skills, and reading composite measures suggest that genetic factors may be more important as a cause for reading disability among children with higher IQ scores than among those with lower IQ scores. To investigate the genetic etiology of reading disability further, measures of word recognition, phonological decoding, orthographic coding, and phoneme awareness were obtained from a total of 465 twin pairs with a positive school history of reading problems. The basic and extended DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data were employed to investigate the etiology of group deficits in reading and language skills, as well as to assess differential genetic etiology for the reading-related measures as a function of IQ. Data from 168 sibling pairs (drawn from the twins' families), including fraternal twin pairs and their siblings, as well as non-twin siblings of identical twins were subjected to single-marker analyses using the DF basic linkage model to examine evidence for linkage of a quantitative-trait locus (QTL) for reading and language deficits to the short arm of chromosome 6. Lastly, to investigate the possible differential influence of this QTL as a function of IQ, the sibling pair data were fitted to an extension of the DF basic linkage model. Results indicated that reading and language deficits are significantly heritable and that differential genetic influences as a function of IQ are evident for measures of word recognition and phonological decoding. Results obtained from linkage analyses confirmed the presence of a QTL on chromosome 6p that influences phonological and orthographic skills, as well as phoneme awareness measures, and suggest that this QTL may influence phoneme awareness differentially as a function of IQ: however, future analyses with considerably larger samples are needed to test the hypothesis of differential QTL influence more rigorously.     

Differential assortative mating found for academic and demographic variables as a function of time of assessment

The purpose of this study was to examine changes in spousal similarity that occur as a function of time of assessment and to assess the extent to which assortment is a function of initial versus realized similarity. Similarity for academic achievement test scores obtained when adults were in elementary and high-school grades was examined in approximately 170 couples. Similarity for occupational and educational traits achieved in adulthood and during marriage was also assessed. The data suggest small but significant assortative mating for test data obtained while husbands and wives were in elementary school. This is in contrast to the larger and significant spousal correlations observed for high-school test scores. Further adjustment procedures indicated that most of the significant high-school test score correlations remained, even after elementary school academic abilities were controlled for. Moreover, spousal correlations for academic-related variables assessed after marriage such as occupation and college education, were only slightly higher than high-school test score correlations and showed some shrinkage after controlling for school-aged academic performance. Some minor convergence was found for one of the variables assessed after marriage using a multiple regression procedure advocated by Price and Vandenberg (1980). The discontinuity in assortment found for elementary, high-school, and adult variables is related to the mate selection procedure and how it appears to be based on the phenotype best approximating that of an adult.     

Latent inhibition as a function of schizotypality and gender: implications for schizophrenia.

In three within-subject experiments, we demonstrated that preexposure to an irrelevant stimulus interfered with performance when that stimulus subsequently predicted the correct location of a target stimulus. This latent inhibition-like effect (LI) was manifest in response time measures, but not errors. As with other related paradigms, LI was a function of an interaction between schizotypy-level and gender. Low schizotypal females and high schizotypal males exhibited significant LI, while high schizotypal females and low schizotypal males failed to produce LI effects. The results, similar to findings with schizophrenic patients, suggest a sexual dimorphism of cognitive dysfunction in schizophrenia, particularly in regard to the processing of irrelevant stimuli.