Crossover Pattern Research Articles

Structured Parenting of Toddlers at High Versus Low Genetic Risk: Two Pathways to Child Problems

ObjectiveLittle is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for psychopathology. MethodThe sample included 290 linked sets of adoptive families and birth mothers and 95 linked birth fathers. Genetic risk was assessed via birth mother and birth father psychopathology (anxiety, depression, antisociality, and drug use). Structured parenting was assessed via microsocial coding of adoptive mothers' behavior during a cleanup task. Toddler behavior problems were assessed with the Child Behavior Checklist. ResultsControlling for tempera mental risk at 9 months, there was an interaction between birth mother psychopathology and adoptive mothers' par enting on toddler behavior problems at 18 months. The interaction indicated two pathways to child problems: structured parenting was beneficial for toddlers at high genetic risk but was related to behavior problems for toddlers at low genetic risk. This crossover interaction pattern was replicated with birth father psychopathology as the index of genetic risk. ConclusionsThe effects of structured parenting on toddler behavior problems varied as a function of genetic risk. Children at genetic risk might benefit from parenting interventions during toddlerhood that enhance structured par enting. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(11):1102–1109.

A positive but complex association between meiotic double-strand break hotspots and open chromatin in Saccharomyces cerevisiae

During meiosis, chromatin undergoes extensive changes to facilitate recombination, homolog pairing, and chromosome segregation. To investigate the relationship between chromatin organization and meiotic processes, we used formaldehyde-assisted isolation of regulatory elements (FAIRE) to map open chromatin during the transition from mitosis to meiosis in the budding yeast Saccharomyces cerevisiae. We found that meiosis-induced opening of chromatin is associated with meiotic DSB hotpots. The positive association between open chromatin and DSB hotspots is most prominent 3 h into meiosis, when the early meiotic genes DMC1 and HOP1 exhibit maximum transcription and the early recombination genes SPO11 and RAD51 are strongly up-regulated. While the degree of chromatin openness is positively associated with the occurrence of recombination hotspots, many hotspots occur outside of open chromatin. Of particular interest, many DSB hotspots that fell outside of meiotic open chromatin nonetheless occurred in chromatin that had recently been open during mitotic growth. Finally, we find evidence for meiosis-specific opening of chromatin at the regions adjacent to boundaries of subtelomeric sequences, which exhibit specific crossover control patterns hypothesized to be regulated by chromatin.

Hypertension as a cause of lower than expected death rates from coronary artery disease among blacks.

Coronary risk factors are more prevalent among blacks than whites in the United States. It is therefore paradoxical that age-adjusted death rates for coronary artery disease (CAD) are similar in the two racial groups. The major risk factor for CAD that is more common among blacks than whites is hypertension, which increases the risk of CAD by two- to fourfold, depending on the presence of smoking, hypercholesterolemia, or other factors. Two general hypotheses have been advanced to explain the lower than expected CAD rates among blacks: (1) the presence of some protective factors, such as increased levels of high density lipoprotein cholesterol (HDL); or (2) selective loss of CAD-prone black individuals due to other causes of mortality. Analysis of age-specific death rates from the vital statistics records strongly suggests that differential survival in the black and white populations, i.e., mortality selection, is the primary explanation of this phenomenon. We sought to test this hypothesis by examining an entirely independent data base. Data from the National Hospital Discharge Survey for the years 1973-1984 were evaluated to determine whether there were age-related differences in case-fatality rates between whites and blacks, and whether a crossover pattern in mortality could be discerned. The results demonstrate that in-hospital case-fatality rates for acute myocardial infarction (MI) were 10% to 70% higher for each of the 10-year age groups for blacks up to age 70 years, at which time a crossover occurred. The median age at which death due to MI occurred in blacks was approximately 5 years earlier than in whites.(ABSTRACT TRUNCATED AT 250 WORDS)

Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans

Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.

Response to Dawson and Arkes

The Authors Reply:— Drs. Dawson and Arkes are to be commended on their detailed analysis of our paper. However, as our response indicates, their analysis fails to affect the interpretation of the data we reported. Drs. Dawson and Arkes express concern that our study did not provide the opportunity for residents to list a differential diagnosis for the patient’s chest pain and that we interpreted cross-sectional data as if they were longitudinal data. What they fail to realize is that in the emergency setting, even with a differential diagnosis in mind, a physician must ultimately make a decision as to whether or not to recommend thrombolysis. At least five studies (not conducted by any of us) have demonstrated that African-American patients are less likely to receive thrombolysis under this circumstances. Our concern was not with the role of race in the recommendation of thrombolysis. Rather, we were interested in the degree to which racial bias as measured by a test of implicit race attitude (the IAT) would predict physicians’ recommendation of thrombolysis to black versus white patients. As is routine in such studies (and in the situations physicians commonly face), we designed the vignette to be ambiguous so as to test the direction of decisions that individual doctors would follow. Indeed, we found that IAT scores are correlated with treatment decisions, and that this correlation is opposite for black and white patients. Additionally, given that these are cross-sectional data, we carefully offered no causal claims in the article. Nor do we make any claim regarding the mechanism that produces this relationship. Regarding the use of terms such as “increasing time for association,” “racial preference,” “racial bias,” and “pro-white/pro-black scores,” we agree that these do not represent a sequence of synonyms. However, these terms are appropriate for the context in which they appear in the manuscript and did not seem to mislead our own internal reviewers, the JGIM peer reviewers, or the editors. Regarding our analyses, we understand why Dawson and Arkes were tempted to interpret the interaction plot the way they did. Across social and medical science it is common for scientists to graph interactions with plots depicting both the interaction variance and the main effect variance even though the statistical test of the interaction refers only to the pure (i.e., unique) interaction variance. As such, one is tempted to interpret the means (in the case of a bar graph) or the data points on a line graph (i.e., the four data points the authors refer to and for which a bar graph was provided). However, it is a mistake to interpret the means as part of the interaction when one is interested purely in the nature of the interaction. Interaction plots such as these are not pure interaction plots; they contain variance from main effects. To the extent that main effects are non-zero, an interaction graph will not appear to be a crossover interaction. Any pure interaction looks exactly the same; as a cross-over pattern (see Ralph Rosnow and Robert Rosenthal, 1991).1 Thus, a re-interpretation of our result on this basis is incorrect. Our data show that as physicians’ bias against blacks increased, recommendations decreased. This was the reverse for white patients. This was our modest conclusion, and the one we stand by. We cannot abide by Dawson and Arkes’ suggestion to interpret the behavior of doctors at specific points along the continuum. Finally, due to space limitations, we did not include a detailed discussion of alternative hypotheses. This limitation cannot affect the integrity of the study itself, and we appreciate that Dawson and Arkes have provided these on our behalf.

Validity and utility of subtyping anorexia nervosa

The purpose of this article is to review the available literature that addresses the predictive validity and utility of subtyping patients with anorexia nervosa (AN) into binge/purge and restrictor subtypes. Literature was reviewed including studies that compared individuals with subtype diagnoses on clinical and outcome variables as well as more recent research examining the frequency of diagnostic crossover. Several studies found that in general the binge/purge subtype patients have more psychopathology, tend to be older, and tend to have a worse outcome. More recent studies which have examined diagnostic crossover suggest that the rate of crossover from the restrictor subtype to the binge/purge subtype is substantial. Crossover from the binge/purge to the restrictor subtype appears to occur less commonly. There is also literature documenting crossover from AN to bulimia nervosa (BN) and a small literature looking at crossover from BN to AN. The results of this article suggest that although there is generally progression from restrictor AN to binge/purge AN to BN in a sizeable number of patients, other crossover patterns can be seen as well and the amount of crossover is quite large. This suggests a lack of predictive validity for subtypes.

Interacting quantum wires: A possible explanation for the 0.7 anomalous conductance

Abstract We investigate an effective one-dimensional conducting channel considering both the contact umklapp and the Coulomb electron–electron interaction. We show that, at low electronic density, the proximity to the Wigner crystal reproduces the anomaly in conductance at 0.7 G 0 . The crucial ingredient of our theory is the fact that the gate voltage acts as a bias controlling the intensity of the umklapp term. At large gate voltages, the umklapp vanishes and we obtain a conducting quantum wire with a perfect conductance. At low gate voltages, the Wigner crystal is pinned by the umklapp term, giving rise to an insulating behavior with vanishing conductance. This crossover pattern has a transition point which can be identified with the anomalous conductance around 0.7 G 0 . This picture is obtained within the framework of a renormalization group calculation. The conductance static regime is achieved by taking first the limit of finite length and then the limit of zero frequency.

Flexible neural mechanisms of cognitive control within human prefrontal cortex

A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) were examined that, in a prior study, exhibited contrasting temporal dynamics between older and younger adults during performance of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit a proactive control pattern (primarily cue-based activation), whereas in older adults a reactive control pattern was found (primarily probe-based activation). In the current study, we found that following a period of task-strategy training, these older adults exhibited a proactive shift within a subset of the PFC regions, normalizing their activity dynamics toward young adult patterns. Conversely, under conditions of penalty-based monetary incentives, the younger adults exhibited a reactive shift some of the same regions, altering their temporal dynamics toward the older adult baseline pattern. These experimentally induced crossover patterns of temporal dynamics provide strong support for dual modes of cognitive control that can be flexibly shifted within PFC regions, via modulation of neural responses to changing task conditions or behavioral goals.

Domain-specific regulation of recombination in Caenorhabditis elegans in response to temperature, age and sex.

It is generally considered that meiotic recombination rates increase with temperature, decrease with age, and differ between the sexes. We have reexamined the effects of these factors on meiotic recombination in the nematode Caenorhabditis elegans using physical markers that encompass >96% of chromosome III. The only difference in overall crossover frequency between oocytes and male sperm was observed at 16 degrees . In addition, crossover interference (CI) differs between the germ lines, with oocytes displaying higher CI than male sperm. Unexpectedly, our analyses reveal significant changes in crossover distribution in the hermaphrodite oocyte in response to temperature. This feature appears to be a general feature of C. elegans chromosomes as similar changes in response to temperature are seen for the X chromosome. We also find that the distribution of crossovers changes with age in both hermaphrodites and females. Our observations indicate that it is the oocytes from the youngest mothers-and not the oldest-that showed a different pattern of crossovers. Our data enhance the emerging hypothesis that recombination in C. elegans, as in humans, is regulated in large chromosomal domains.

Supercritical fluid extraction of shiitake oil: Curve modeling and extract composition

Lentinula edodes (Berk.) Pegler or shiitake is the second most cultivated mushroom in the world. Therapeutic characteristics like antioxidant and antimicrobial activities are attributed to shiitake, which is a source of proteins, carbohydrates, mineral and vitamins. In this work, supercritical fluid extraction of shiitake oil was investigated with the purpose of process modeling. Extraction curves were obtained at 303, 313 and 323 K, from 150 to 350 bar, and flow rate from 3.33 to 6.67 g/min. Process yields were up to 1.01% (w/w), with yield isotherms showing a crossover pattern between 150 and 200 bar. Different mass transfer models, based on mass balance of the extractor and empirical correlations, were used to describe the experimental data. The modeling shows a good fit with experimental data. Additionally, the oil composition was obtained by gas chromatography–mass spectrometry analysis, and the main components detected were palmitic acid, linoleic acid and ergosterol.

Centromere-linkage in the turbot (Scophthalmus maximus) through half-tetrad analysis in diploid meiogynogenetics

Seventy nine microsatellite markers selected across all linkage groups (LG) from a previous turbot genetic map were studied in a diploid meiogynogenetic family for centromere mapping using half-tetrad analysis. Significant deviations from Mendelian segregation were observed at 25% loci analyzed. The clustering of distorted loci at specific LGs, suggested the existence of genes of different deleterious effects. The lack of Mendelian segregation distortion at 1 day and 10 days post-hatching larvae at these loci precluded an explanation based on aberrant meiotic segregation. Heterozygote frequency distribution in gynogenetic offspring showed close to 50% values above 0.667, which suggested high chiasma interference in turbot. Complete interference appeared as the best fitting function when estimating centromere position. However, Kosambi and Haldane functions performed better at specific LGs as a consequence of the variable crossover pattern of centromere-distant markers among LG. Great concordance between half-tetrad data and the positions previously reported in the turbot map was observed. Most centromeres were localized with an error around or below 5 cM and closely linked markers exist now in 8 LGs. Centromere location was mostly in accordance with previous karyotypic information.

Pressure–heart rate product changes from childhood to adulthood in a biracial population — a crossover phenomenon: the Bogalusa Heart Study

Cardiovascular (CV) hemodynamic characteristics are major risk factors for heart disease. Cross-sectional surveys of 5,976 individuals (47% males; 63% Whites), aged 4 to 44 years, and a subset of 1,365 individuals examined both in childhood and in adulthood were examined for blood pressure and heart rate along with cardiovascular risk factors. In early childhood, Whites showed significantly faster heart rate than Blacks; at adolescence, blood pressure levels became greater in Blacks. The systolic blood pressure times heart rate, the double product, in childhood (Whites > Blacks) is reversed in adulthood (Blacks > Whites). A “crossover” at the young adult age occurs. The crossover was observed at around 20 years in females and 25 years in males. Multivariate analyses indicated age, race, and homeostasis model of insulin resistance were independently related to the double product. Further, there was a significant interaction between age and race. These hemodynamic parameters change with increasing age with a crossover pattern of the pressure-rate product between the different races in young adults. Changes in the double product suggest a greater sympathetic nervous system activation occurring in Blacks reaching adulthood. Although not measured, central vs. peripheral sympathetic–parasympathetic balance, which determine hemodynamic characteristics, is influenced by increasing obesity and carbohydrate-insulin metabolic changes in adulthood. Further, hemodynamic parameters create a cardiovascular burden over time producing subtle, subclinical disease of the cardiovascular system. Control of obesity in the population remains critical.

Bridging the gap: the creation of continuity by men on the verge of retirement

ABSTRACTThe aim of this study is to examine the means by which men on the verge of retirement create continuity or bridges between their past and present in their autobiographical narratives. Based on Whitbourne's ‘lifespan construct model of adaptation’, 56 Israeli men on the verge of retirement were asked to relate their ‘life stories’ and ‘life scenarios’ (their vision of the future). Their bridging strategies were examined using qualitative structural analyses, focusing on the ‘crossovers’ to the future in the ‘life stories’, and those to the past in their ‘life scenarios’. The findings show three main bridging patterns in the life stories and three in the life scenarios. Each was associated with differences in the ways that the men were coping emotionally with the transition to retirement, and pointed to the different ways by which they used continuity to cope with the anxieties aroused by their impending retirement. After trying to account for the greater frequency of bridging attempts in the ‘scenarios’ than the ‘life stories’, the discussion elaborates on the different bridging strategies and their associated features. The findings suggest that the identification of crossover patterns in life stories and life scenarios may be a useful tool for assessing a person's coping abilities and adjustment to difficult transitions.

Development and Validation of Transtheoretical Model Measures for Bulgarian Adolescent Non-Smokers

The goal of this study was to develop, translate, and evaluate measures for decisional balance and situational temptations for Bulgarian adolescent nonsmokers and to test the predicted relationships with stages of change. Students in the last grades of high school (15–19 years old) recruited in 12 randomly selected schools participated in the study. Data from the 369 nonsmokers (61.8% female, mean age 16.4 years, 97.1% Bulgarian) were used in the measurement development. A two-factor model for decisional balance (CFI =. 94) and a hierarchical three-factor model for temptations (CFI =. 90) demonstrated the best fit. The predicted crossover pattern for decisional balance and decreasing trend for temptations across the stages of change was verified. Both measures demonstrated tau-equivalent invariance across gender, in addition to good psychometric properties. These results, with the caveat of the noted limitations, support the cross-cultural validity of these transtheoretical model (TTM) constructs and indicate that they can be used as a basis for development of smoking prevention interventions.

MLH1-focus mapping in birds shows equal recombination between sexes and diversity of crossover patterns

Using immunolocalization of the mismatch-repair protein MLH1 in oocytes and spermatocytes of the Japanese quail and the zebra finch, we estimated the average amount of recombination in each sex of both species. In each case the number of MLH1 foci is statistically equivalent in males and females and the resulting sex-averaged map lengths are 2800 cM in the Japanese quail and 2275 cM in the zebra finch. In the Japanese quail the MLH1 foci are regularly distributed along the macrobivalents and recombination rates per Mb pair are somewhat lower compared to the chicken. In the zebra finch the MLH1 foci on the macrobivalents are substantially reduced in number relative to the Japanese quail and they show remarkable localization in both sexes. It is proposed that the lack of sex-dependent differences in recombination might be an extended feature among birds and that the different recombination patterns observed here reflect different controls of crossing over in spite of similarities regarding karyotypic asymmetry and DNA content. We discussed possible causes of the differences between birds and mammals, which show sex-dependent recombination differences.

Lack of meiotic crossovers during oogenesis in an apparent 45,X Ullrich–Turner syndrome patient with three children

A woman with apparent 45,X Ullrich-Turner syndrome was ascertained after the birth of three girls, the last being growth retarded due to a del(X)(p22.11) of grand-paternal origin. In this woman no del(X)-chromosome was detectable in blood by FISH or PCR. Fibroblast cultures from four different biopsies of her skin varied from having 45,X only to mosaic 46,X,del(X) to 46,X,del(X) only. In one fibroblast culture, a few cells with two del(X) chromosomes were found, probably remnants of a paternal dicentric X that caused the condition. Her three daughters were born when she was 29, 31, and 39 years old, respectively, indicating that disomy for the distal half of Xp is not required for normal folliculogenesis. When studying the crossover pattern of her daughters' maternal X-chromosomes, it turned out that one daughter had an X that was exclusively grand-maternal, one daughter lacked crossovers on Xq, and one daughter lacked crossovers on Xp. This suggests that univalent X-chromosomes were present in the Ullrich-Turner patient's primordial egg cells, either because there was only a single X-chromosome present (a 45,X primary oocyte), or because the X-chromosome was a partially or completely unpaired in pachytene, indicating a problem with chromosome association and synapsis formation.

Religious attendance and mortality: Implications for the black-white mortality crossover

This study investigates the relationships among religious attendance, mortality, and the black-white mortality crossover. We build on prior research by examining the link between attendance and mortality while testing whether religious involvement captures an important source of population heterogeneity that contributes to a crossover Using data from the Established Populations for Epidemiologic Studies of the Elderly, we find a strong negative association between attendance and mortality. Our results also show evidence of a racial crossover in mortality rates for both men and women. When religious attendance is modeled in terms of differential frailty, clear gender differences emerge. For women, the effect of attendance is race- and age-dependent, modifying the age at crossover by 10 years. For men, however; the effect of attendance is not related to race and does not alter the crossover pattern. When other health risks are modeled in terms of differential frailty, wefind neither race nor age-related effects. Overall, the results highlight the importance of considering religious attendance when examining racial and gender differences in age-specific mortality rates.

Evidence of Meiotic Crossover Control in Saccharomyces cerevisiae Through Mec1-Mediated Phosphorylation of Replication Protein A

Replication protein A (RPA) is the major single-stranded DNA-binding protein in eukaryotes, essential for DNA replication, repair, and recombination. During mitosis and meiosis in budding yeast, RPA becomes phosphorylated in reactions that require the Mec1 protein kinase, a central checkpoint regulator and homolog of human ATR. Through mass spectrometry and site-directed mutagenesis, we have now identified a single serine residue in the middle subunit of the RPA heterotrimer that is targeted for phosphorylation by Mec1 both in vivo and in vitro. Cells containing a phosphomimetic version of RPA generated by mutation of this serine to aspartate exhibit a significant alteration in the pattern of meiotic crossovers for specific genetic intervals. These results suggest a new function of Mec1 that operates through RPA to locally control reciprocal recombination.

Grain-Size Sorting in Meander Bends Containing Large Woody Debris

Few studies have investigated the effects of large woody debris (LWD) on patterns of grain-size sorting in meander bends. In unobstructed meander bends, a characteristic pattern of sediment sorting has been observed in which the coarse and fine particles "cross over" through a bend. This field-based study examines the influence of LWD on spatial patterns of grain-size sorting in three meander bends of a low-energy stream in northern Illinois. The results of this study indicate that, in some cases, LWD substantially modifies patterns of grain-size sorting in low-gradient meander bends. Grain-size patterns in one study bend generally correspond with those observed in studies of other meander bends, but patterns in the two other bends are lacking the clear, characteristic crossover pattern of coarse and fine sediments. The detailed nature of the modifications appears to be highly dependent on the particular arrangement of LWD in a bend.

SNP microarray analysis for genome-wide detection of crossover regions

There is a great deal of interest in understanding the non-random distribution of recombination events over the human genome, because it has important implications for using linkage disequilibrium (LD) to identify human disease genes. So far, only a few recombination hotspots in the human genome have been characterised and the identification of new crossover hotspots will contribute to a better understanding of the mechanisms that govern their formation and distribution. This study shows that high-density single nucleotide polymorphism (SNP) arrays, together with the presented analysis method, are an appropriate tool for generating a whole-genome recombination pattern and for detecting new crossover regions with enhanced recombination frequency. Based on the genotype data of 16 members of a Caucasian three-generation family, we identified 825 crossover regions. The average recombination frequency of females and males was 0.77 and 0.56 cM/Mb, respectively. We detected 24 crossover regions showing elevated recombination activity, which comprised known hotspots, like the MHC II region, confirming the non-random distribution of recombination events along the genome. Interestingly, 29.2% of the identified crossover hotspot regions overlapped with regions flanked by segmental duplications published by Bailey et al. (Science 297:1003-1007, 2002) suggesting that segmental duplications and crossover hotspot regions are mechanistically linked. By extrapolating the results of the present study, we conclude that it might be feasible, at least in part, to estimate to what extent the block-like pattern of LD exactly relies on the genome-wide crossover pattern using the next generation high-density SNP microarrays.