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Results for “crossover”

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PubMed1994

Cleavage of double-crossover molecules by T4 endonuclease VII.

DNA double-crossover molecules containing two Holliday junctions have been prepared and treated with endonuclease VII, the resolvase from bacteriophage T4. One molecule contains antiparallel double-helical domains, and the other molecule contains parallel domains. The parallel double-crossover model system has been made tractable by closing the free ends of the molecule, to convert it to a catenane. The products resulting from the two substrates differ substantially. The molecule containing antiparallel helical domains is cleaved three nucleotides 3' to the crossover points, in a fashion similar to single Holliday junction analogs. The molecule containing parallel helical domains is cleaved, but the major points of scission are five nucleotides 5' to a branch point on the crossover strands and six nucleotides 3' to the same branch point on the non-crossover strands. The major sites of scission reflect features of molecular symmetry in each case, suggesting that the resolvase recognizes structural features. The cleavage results suggest that the antiparallel structure is the natural substrate, if the Holliday junction is unconstrained within the cell. It is straightforward to reconcile antiparallel Holliday junctions with the conventional parallel paradigm of recombination. Nevertheless, the cleavage of the parallel molecule shows that a parallel substrate could also be cleaved symmetrically by endonuclease VII (but with different products) if the molecule were constrained to assume that conformation within the cell.

Base Sequence↗

PubMed2001

Iron(III) spin-crossover compounds with a wide apparent thermal hysteresis around room temperature.

The magnetic properties of the spin-crossover compounds, [Fe(qsal)2]NCSe-MeOH (1) and [Fe(qsal)2]NCSe-CH2Cl2 (2), have been measured. We have discovered that both compounds 1 and 2 exhibit a wide thermal hysteresis loop of 140 K (T(1/2) upward arrow = 352 K and T(1/2) downward arrow = 212 K) and 180 K (T(1/2) upward arrow = 392 K and T(1/2) downward arrow = 212 K), respectively, in the first cycle. Thermogravimetric analysis shows that solvent molecules escape from compounds 1 and 2 around 340 and 395 K, respectively. This means that the hysteresis loops observed for the first cycle are only apparent ones. Following the first loop, they show a two-step spin-crossover in warming mode. The so-called "step 1" and "step 2" are centered around T(1/2(S1)) upward arrow = 215 K and T(1/2(S2)) upward arrow = 282 K, respectively. On the other hand, a one-step spin-crossover occurs at T(1/2) downward arrow = 212 K in cooling mode. The hysteresis widths can be estimated to be 3 K (step 1) and 70 K (step 2), assuming that the widths in steps 1 and 2 are defined as the differences between T(1/2(S1)) upward arrow and T(1/2) downward arrow, and T(1/2(S2)) upward arrow and T(1/2) downward arrow, respectively. The hysteresis width of 70 K in step 2 is one of the widest values reported so far for spin-crossover complexes. It is thought that the cooperativity operating in the complexes arises mainly from the intermolecular pi interactions between quinoline and phenyl rings. Using a previously reported model, we are able to simulate the hysteresis loop with a two-step spin-crossover in warming mode and a one-step transition in cooling mode.

Journal Article↗

PubMed1999

The crossover of strain from school principals to teachers and vice versa.

The study investigated crossover of stress and strain in the workplace on a sample of 47 school principals and 183 teachers in Israeli elementary schools. The main goal of this study was to examine whether the crossover effect found among couples in the family also exists in the workplace. A 2nd aim of the study was to unravel the mechanisms that account for the crossover process. Using structural equation modeling, the authors found a significant crossover of job-induced tension but not of burnout from principals to teachers and vice versa. Being undermined by their principals elevated teachers' burnout and job-induced tension. This is the 1st study to demonstrate crossover of strain in the workplace and to discuss the implications of contagious job-induced tension in work environments.

Administrative Personnel↗

PubMed1985

Crossover and noncrossover designs in four-point parallel line analgesic assays.

Fifty-nine analgesic investigations designed as four-point parallel line crossover assays were examined. Sum of pain intensity differences (SPID) and total pain relief (TOTPAR) were the subjective response measures. Separate analyses with four-point crossover data and first-dose data (noncrossover) allowed comparison within each study of these two approaches. The crossover analysis allows for removal of the subject component of variance, which in these studies was a substantial fraction of the error variance (0.49 for SPID; 0.56 for TOTPAR). For this type of study, 2.4 times as many subjects would have to be recruited in a noncrossover design to obtain precision equivalent to that of the crossover design. Thus efficiency considerations argue for the crossover design in cases in which a treatment carryover effect may be assumed to be negligible.

Analgesics↗

PubMed2003

Carotid-carotid crossover bypass: is it a durable procedure?

PURPOSE: Reconstruction of a diseased common carotid artery may necessitate direct repair via aortic artery-based revascularization. However, carotid-carotid artery crossover grafting is an alternative extra-anatomic option that obviates the need for median sternotomy. We analyzed our results with carotid-carotid artery crossover bypass surgery. METHODS: Data were analyzed for all patients undergoing carotid-carotid crossover bypass surgery from 1995 to 2000. Data on patient demographics, indications for surgery, perioperative morbidity and mortality, and graft patency were retrieved from a vascular surgery data base and hospital records. Stroke-free survival and graft patency were determined with life table methods. RESULTS: Over 5 years, 24 carotid-carotid artery crossover bypass procedures were performed to treat both symptomatic (n = 19, 79%) and asymptomatic (n = 5, 17%) disease. Nine procedures (38%) were performed in men, 3 (13%) in patients with diabetes, 12 (50%) in active smokers, and 2 in patients with a history of Takayasu arteritis. Patient mean age was 63 years (range, 38-79 years). Twenty-three patients (96%) received polytetrafluoroethylene conduit grafts, and the remaining patients received vein grafts. Ten (42%) patients underwent concomitant endarterectomy. There were no perioperative deaths. One patient (4%) had asymptomatic early occlusion, one had transient neurologic deficit (4%), one (4%) required additional surgery because of bleeding, and one (4%) had a perioperative cerebrovascular accident (stroke). Three (17%) asymptomatic late occlusions were identified at 11, 57, and 64 months, respectively. Mean follow-up was 30 months (range, 1-70 months). Primary patency was 88%, and secondary patency was 92% at 3 years. Stroke-free survival was 94% at 4 years. CONCLUSION: Carotid-carotid artery crossover bypass surgery is a safe and durable procedure. Its use precludes the need for median sternotomy and provides acceptable stroke-free survival.

Adult↗

PubMed2005

Hydrophobic hydration from small to large lengthscales: Understanding and manipulating the crossover.

Small and large hydrophobic solutes exhibit remarkably different hydration thermodynamics. Small solutes are accommodated in water with minor perturbations to water structure, and their hydration is captured accurately by theories that describe density fluctuations in pure water. In contrast, hydration of large solutes is accompanied by dewetting of their surfaces and requires a macroscopic thermodynamic description. A unified theoretical description of these lengthscale dependencies was presented by Lum, Chandler, and Weeks [(1999) J. Phys. Chem. B 103, 4570-4577]. Here, we use molecular simulations to study lengthscale-dependent hydrophobic hydration under various thermodynamic conditions. We show that the hydration of small and large solutes displays disparate dependencies on thermodynamic variables, including pressure, temperature, and additive concentration. Understanding these dependencies allows manipulation of the small-to-large crossover lengthscale, which is nanoscopic under ambient conditions. Specifically, applying hydrostatic tension or adding ethanol decreases the crossover length to molecular sizes, making it accessible to atomistic simulations. With detailed temperature-dependent studies, we further demonstrate that hydration thermodynamics changes gradually from entropic to enthalpic near the crossover. The nanoscopic lengthscale of the crossover and its sensitivity to thermodynamic variables imply that quantitative modeling of biomolecular self-assembly in aqueous solutions requires elements of both molecular and macroscopic hydration physics. We also show that the small-to-large crossover is directly related to the Egelstaff-Widom lengthscale, the product of surface tension and isothermal compressibility, which is another fundamental lengthscale in liquids.

Biophysical Phenomena↗

PubMed2003

Crossover interference in humans.

Crossing-over between homologous chromosomes facilitates proper disjunction of chromosomes during meiosis I. In many organisms, gene functions that are essential to crossing-over also facilitate the intimate chromosome pairing called "synapsis." Many organisms--including budding yeast, humans, zebrafish, Drosophila, and Arabidopsis--regulate the distribution of crossovers, so that, most of the time, each chromosome bundle gets at least one crossover while the mean number of crossovers per chromosome remains modest. This regulation is obtained through crossover interference. Recent evidence suggests that the organisms that use recombination functions to achieve synapsis have two classes of crossovers, only one of which is subject to interference. We statistically test this two-pathway hypothesis in the CEPH data and find evidence to support the two-pathway hypothesis in humans.

Animals↗

PubMed1993

Physical mapping of meiotic crossover events in a 200-kb region of Neurospora crassa linkage group I.

We propose a general restriction fragment length polymorphism-based strategy to analyze the distribution of meiotic crossover events throughout specific genetic intervals. We have isolated 64 recombinant chromosomes carrying independent meiotic crossover events in the genetic interval eth-1-un-2 on linkage group I of Neurospora crassa. Thirty-eight crossover events were physically mapped with reference to a 200-kb region cloned by chromosome walking, using N. crassa lambda and cosmid libraries. Crossovers were homogeneously distributed at intervals of 5.0 +/- 2.3 kb along the entire cloned interval. The ratio of physical to genetic distance appears to be higher in the region than in the overall N. crassa genome, suggesting that recombinational activity is less in large chromosomes than in small ones. The present work provides a method for defining the centromeric-telomeric orientation of single cloned DNA fragments. Their physical distance can also be estimated with respect to linked loci, provided that crossover events are distributed homogeneously in the interval. This strategy overcomes typical difficulties in defining the position and direction of chromosome walking steps on conventional linkage maps.

Chromosome Mapping↗

PubMed2001

Negative crossover interference in maize translocation heterozygotes.

Negative interference describes a situation where two genetic regions have more double crossovers than would be expected considering the crossover rate of each region. We detected negative crossover interference while attempting to genetically map translocation breakpoints in maize. In an attempt to find precedent examples we determined there was negative interference among previously published translocation breakpoint mapping data in maize. It appears that negative interference was greater when the combined map length of the adjacent regions was smaller. Even positive interference appears to have been reduced when the combined lengths of adjacent regions were below 40 cM. Both phenomena can be explained by a reduction in crossovers near the breakpoints or, more specifically, by a failure of regions near breakpoints to become competent for crossovers. A mathematical explanation is provided.

Chromosome Mapping↗

PubMed2003

Crossover interference in Saccharomyces cerevisiae requires a TID1/RDH54- and DMC1-dependent pathway.

Two RecA-like recombinases, Rad51 and Dmc1, function together during double-strand break (DSB)-mediated meiotic recombination to promote homologous strand invasion in the budding yeast Saccharomyces cerevisiae. Two partially redundant proteins, Rad54 and Tid1/Rdh54, act as recombinase accessory factors. Here, tetrad analysis shows that mutants lacking Tid1 form four-viable-spore tetrads with levels of interhomolog crossover (CO) and noncrossover recombination similar to, or slightly greater than, those in wild type. Importantly, tid1 mutants show a marked defect in crossover interference, a mechanism that distributes crossover events nonrandomly along chromosomes during meiosis. Previous work showed that dmc1Delta mutants are strongly defective in strand invasion and meiotic progression and that these defects can be partially suppressed by increasing the copy number of RAD54. Tetrad analysis is used to show that meiotic recombination in RAD54-suppressed dmc1Delta cells is similar to that in tid1; the frequency of COs and gene conversions is near normal, but crossover interference is defective. These results support the proposal that crossover interference acts at the strand invasion stage of recombination.

Cell Cycle Proteins↗

PubMed2003

The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast.

Current models for meiotic recombination require that crossovers derive from the resolution of a double-Holliday junction (dHJ) intermediate. In prokaryotes, enzymes responsible for HJ resolution are well characterized but the identification of a eukaryotic nuclear HJ resolvase has been elusive. Indirect evidence suggests that MUS81 from humans and fission yeast encodes a HJ resolvase. We provide three lines of evidence that Mus81/Mms4 is not the major meiotic HJ resolvase in S. cerevisiae: (1) MUS81/MMS4 is required to form only a distinct subset of crossovers; (2) rather than accumulating, dHJ intermediates are reduced in an mms4 mutant; and (3) expression of a bacterial HJ resolvase has no suppressive effect on mus81 meiotic phenotypes. Our analysis also reveals the existence of two distinct classes of crossovers in budding yeast. Class I is dependent upon MSH4/MSH5 and exhibits crossover interference, while class II is dependent upon MUS81/MMS4 and exhibits no interference. mms4 specifically reduces crossing over on small chromosomes, which are known to undergo less interference. The correlation between recombination rate and degree of interference to chromosome size may therefore be achieved by modulating the balance between class I/class II crossovers.

Crossing Over, Genetic↗

PubMed2005

Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot.

Little is known about the factors that influence the frequency and distribution of meiotic recombination events within human crossover hotspots. We now describe the detailed analysis of sperm recombination in the NID1 hotspot. Like the neighbouring MS32 hotspot, the NID1 hotspot is associated with a minisatellite, suggesting that hotspots predispose DNA to tandem repetition. Unlike MS32, crossover resolution breakpoints in NID1 avoid the minisatellite, producing a cold spot within the hotspot. This avoidance may be related to the palindromic nature of the minisatellite interfering with the generation and/or processing of recombination intermediates. The NID1 hotspot also contains a single nucleotide polymorphism (SNP) close to the centre, which appears to directly influence the frequency of crossover initiation. Quantitative gene conversion assays show that this SNP affects the frequency of gene conversion and crossover to a very similar extent, providing evidence that conversions and crossovers are triggered by the same recombination initiating events. The recombination-suppressing allele is over-transmitted to recombinant progeny, and provides the most dramatic example to date of recombination-mediated meiotic drive, of a magnitude sufficient to virtually guarantee that the recombination suppressor will eventually replace the more active allele in human populations.

Base Sequence↗

PubMed2006

Polymorphism in the activity of human crossover hotspots independent of local DNA sequence variation.

Meiotic crossovers in the human genome cluster into highly localized hotspots identifiable indirectly from patterns of DNA diversity and directly by high-resolution sperm typing. Little is known about factors that control hotspot activity and the apparently rapid turnover of hotspots during recent evolution. Clues can, however, be gained by characterizing variation in sperm crossover activity between men. Previous studies have identified single nucleotide polymorphisms within hotspots that appear to suppress crossover activity and which may be involved in hotspot attenuation/extinction. We now analyse a closely spaced pair of hotspots (MSTM1a, MSTM1b) on chromosome 1q42.3, the former being a candidate for a young hotspot that has failed to leave a significant mark on haplotype diversity. Extensive surveys of different men revealed substantial polymorphism in sperm crossover frequencies at both hotspots, but with very different patterns of variation. Hotspot MSTM1b was active in all men tested but with widely differing crossover frequencies. In contrast, MSTM1a was active in only a few men and appeared to be recombinationally inert in the remainder, providing the first example of presence/absence polymorphism of a human hotspot. Haplotype analysis around both hotspots identified active and suppressed men sharing identical haplotypes, establishing that these major variations in the presence/absence of a hotspot and in quantitative activity are not caused by local DNA sequence variation. These findings suggest a role for distal regulators or epigenetic factors in hotspot activity and provide the first direct evidence for the rapid evolution of recombination hotspots in humans.

Chromosome Mapping↗

PubMed2001

Cross-facial nerve grafting as an adjunct to hypoglossal-facial nerve crossover in reanimation of early facial paralysis: clinical and electrophysiological evaluation.

Reanimation of a spontaneous and synchronous smile, and sufficient depressor mechanism of the lower lip presents a surgical challenge in facial paralysis. Hypoglossal-facial nerve crossover and cross-facial nerve grafting are the best options if the mimetic muscles around the mouth are still viable in patients in whom the facial nerve was sacrificed at the brainstem. Although good muscle tone and facial motion have been obtained by hypoglossal-facial nerve crossover, smile is dependent on conscious tongue movement. Cross-facial nerve grafting provides a voluntary and emotion-driven smile, but requires two coaptation sites, which leads to substantial axonal loss and a long regeneration time. This method was not successful in activating the depressor mechanism. The first stage is the classic "baby-sitting" procedure, in which the bulk of the mimetic muscles was maintained by the rapid reinnervation of the hypoglossal-facial nerve crossover during the regeneration period of the cross-facial nerve graft, and temporalis muscle transfer to the eyelids is performed. During the second stage, the cross-facial nerve graft that used the thickest zygomaticobuccal branch on the healthy side was coapted with the corresponding branches on the paralyzed side. The hypoglossal-facial nerve crossover continued to innervate the depressor muscles. Good spontaneous smile and sufficient depressor mechanism were achieved by cross-facial nerve grafting and hypoglossal-facial nerve crossover respectively, and these techniques are demonstrated by the authors clinically and electrophysiologically.

Adult↗

PubMed1996

Confounding and exposure trends in case-crossover and case-time-control designs.

As with ordinary studies, both case-crossover and case-time-control studies can suffer from confounding, including confounding by indication. In a case-crossover analysis, confounding by fixed (constant) characteristics is eliminated by pairing of cases to themselves, at the possible cost of introducing bias due to time trends in exposure. A case-time-control analysis can correct case-crossover results only for bias due to such time trends. If an uncontrolled confounder (such as disease severity) is present, the use of time controls can introduce new confounding, and the case-time-control results may end up either more or less confounded than the ordinary and case-crossover results. The relative confounding in the different approaches depends on details of the relations among the unmeasured confounder, the study exposure, the study disease, and any trend in these variables or their effects. Like an ordinary study, a case-time-control study must assume absence of unmeasured confounders, whether fixed or time-varying. Like a case-crossover study, it must also assume absence of carryover effects and can be more prone to misclassification bias than an ordinary study.

Bias↗

PubMed1997

A comparison of case-crossover and case-control designs in a study of risk factors for hemorrhagic fever with renal syndrome.

The case-crossover design is a new method for studying acute effects of transient exposures, in which cases serve as their own controls. To assess the validity, strengths, and weaknesses of the design, we used both the case-crossover method and the traditional case-control method of multivariate analysis with data collected from 196 cases and 295 hospital controls to study risk factors for hemorrhagic fever with renal syndrome in Korean soldiers. Both case-control and case-crossover methods showed that living in primitive field conditions, exposure to dust, and exposure to rodents were risk factors; use of insecticides or insect repellents was protective. Odds ratios from the case-crossover method were generally somewhat higher for risk factors and lower for protective factors. The case-crossover technique has great potential as a powerful, cost-effective way to assess risk factors for conditions such as infectious diseases and injuries, while avoiding some of the bias and logistical problems of traditional study designs.

Adult↗

PubMed2001

Referent selection in case-crossover analyses of acute health effects of air pollution.

The case-crossover design was proposed for the study of a transient effect of an intermittent exposure on the subsequent occurrence of a rare acute-onset disease. This design can be an alternative to Poisson time series regression for studying the health effects of fine particulate matter air pollution. Characteristics of time-series of particulate matter, including long-term time trends, seasonal trends, and short-term autocorrelations, require that referent selection in the case-crossover design be considered carefully and adapted to minimize bias. We performed simulations to evaluate the bias associated with various referent selection strategies for a proposed case-crossover study of associations between particulate matter and primary cardiac arrest. Some a priori reasonable strategies were associated with a relative bias as large as 10%, but for most strategies the relative bias was less than 2% with confidence interval coverage within 1% of the nominal level. We show that referent selection for case-crossover designs raises the same issues as selection of smoothing method for time series analyses. In addition, conditional logistic regression analysis is not strictly valid for some case-crossover designs, introducing further bias.

Acute Disease↗

PubMed1986

Reaction time crossover as a marker of schizophrenia and of higher functioning.

A factor analysis of reaction time crossover data of 53 schizophrenic patients, 45 first-degree relatives, and 38 controls, previously reported by De Amicis and Cromwell, was performed in order to shed light upon the relationship of crossover to aging, mean reaction time, and general socioeconomic functioning. The aging factor shared variance with getting married and having children, but not with reaction time crossover. Crossover was also found to be independent of reaction time speed among first-degree relatives and control subjects; however, it was correlated with reaction time speed among actively symptomatic schizophrenic patients. Additionally, the relationship of crossover to socioeconomic functioning was found to be negative among the patients, positive among the relatives, and nonexistent among control subjects. Results are discussed in terms of previous reports of higher than normal functioning found in relatives of schizophrenic patients.

Aging↗