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PubMed1990

A putative serine/threonine protein kinase encoded by the segment-polarity fused gene of Drosophila.

The segmented pattern of the Drosophila embryo depends on a regulatory cascade involving three main classes of genes. An early regulatory programme, set up before cellularization, involves direct transcriptional regulation mediated by gap and pair-rule genes. In a second phase occurring after cellularization, interactions between segment-polarity genes are involved in cell communication. Segment-polarity genes are required for pattern formation in different domains of each metamere and act to define and maintain positional information in each segment. The segment-polarity gene fused is maternally required for correct patterning in the posterior part of each embryonic metamere. It is also necessary later in development, as fused mutations lead to anomalies of adult cuticular structures and tumorous ovaries. Here we provide molecular evidence that this gene encodes a putative serine/threonine protein kinase, a new function for the product of a segmentation gene. This result provides further insight into segment-polarity interactions and their role in pattern formation.

Amino Acid Sequence↗
PubMed1997

The repeating segments of the F-actin cross-linking gelation factor (ABP-120) have an immunoglobulin-like fold.

The 120,000 M(r) gelation factor and alpha-actinin are among the most abundant F-actin cross-linking proteins in Dictyostelium discoideum. Both molecules are rod-shaped homodimers. Each monomer chain is comprised of an actin-binding domain and a rod domain. The rod domain of the gelation factor consists of six 100-residue repetitive segments with high internal homology. We have now determined the three-dimensional structure of segment 4 of the rod domain of the gelation factor from D. discoideum using NMR spectroscopy. The segment consists of seven beta-sheets arranged in an immunoglobulin-like (Ig) fold. This is completely different from the alpha-actinin rod domain which consists of four spectrin-like alpha-helical segments. The gelation factor is the first example of an Ig-fold found in an actin-binding protein. Two highly homologous actin-binding proteins from human with similar sequences to the gelation factor, filamin and a 280,000 M(r) actin-binding protein (ABP-280), share conserved residues that form the core of the gelation factor repetitive segment structure. Thus, the segment 4 structure should be common to this subfamily of the spectrin superfamily. The structure of segment 4 together with previously published electron microscopy data, provide an explanation for the dimerization of the whole gelation factor molecule.

Actins↗
PubMed2006

Segmental duplication density decrease with distance to human-mouse breaks of synteny.

Segmental duplications are large genomic segments of recent origin and nearly identical sequence. Segmental duplications account for up to 5% of the human genome and they are often involved in genomic rearrangements and human disease. We developed a rapid computational method to characterize segmental duplications in the mouse and the human genomes according to four sequence assemblies for each species. Segmental duplication content in the mouse genome assemblies has largely changed over the four releases (from 0.2 to 1.2%, 4.5 and 3.0%), while in the four human assemblies duplication content was 4.8, 3.5, 3.7 and 3.7%, respectively. This suggests that cataloguing and assembling duplications has been challenging in both genomes and any interpretation of comparative analyses of duplication content must keep this in perspective to avoid artifacts. Human and mouse segmental duplications are more frequent than expected in regions where there is a syntenic discontinuity and the duplication content in syntenic regions decreases significantly with distance from breakpoints of synteny. These observations indicate that in mouse and human the frequency of segmental duplications is strongly correlated with distance to human and mouse syntenic breaks or the most dynamic regions in evolution..

Animals↗
PubMed2002

Type 1 segmental cutaneous leiomyomatosis.

Cutaneous leiomyomas are rare benign tumours of the skin, which present in multiple disseminated, segmental or solitary forms. The pathogenesis of segmental cutaneous leiomyomatosis is not yet fully known. Most recently two types of segmental manifestation of autosomal dominant inherited diseases were postulated. Type 1 reflects heterozygosity for the underlying mutation with a clinical picture similar to that in a non-mosaic phenotype. In type 2, loss of heterozygosity leads to homo- or hemizygosity with a pronounced segmental manifestation of lesions in the affected segment. In our patient the lesions were restricted to one segment and therefore she most probably has a type 1 segmental cutaneous leiomyomatosis.

Adult↗
PubMed1997

Reproducibility and accuracy of interactive segmentation procedures for image analysis in cytology.

The segmentation of nuclear images is a crucial step in the development of procedures using image analysis for the cytological diagnosis of cancer. The purpose of this study is to evaluate the reproducibility and accuracy of several interactive segmentation methods which can be used in this context. Four methods were studied: a thresholding-based method enabling selection of intensity histogram contrast and brightness, manual tracing with a stylus, and arc- and ellipse-fitting routines. Features of nuclear size and shape were derived from nuclei segmented on repeated occasions by several individuals. Variance component models provided a statistical framework for evaluating the intraobserver and interobserver variability of these measurements in terms of their intraclass correlation coefficients. Of the methods tested, the arc-fitting segmentation method gave the most reproducible results, and thresholding the least. Reproducibility was generally very high both between individuals and for repeated segmentations by a single individual. Accuracies of area measurements for the various methods, as determined with respect to point counting, paralleled the reproducibilities of the methods. Sample size requirements were observed to be more dependent on the biological variability of the tissue sampled than on the particular segmentation method or on the number of individuals performing segmentation.

Cell Biology↗
PubMed2001

Assessment of concordance among genealogical reconstructions from various mtDNA segments in three species of Pacific salmon (genus Oncorhynchus).

Seven segments of mitochondrial DNA (mtDNA), comprising 97% of the mitochondrial genome, were amplified by polymerase chain reaction (PCR) and examined for restriction site variation using 13 restriction endonucleases in three species of Pacific salmon: pink (Oncorhynchus gorbuscha), chum (O. keta) and sockeye (O. nerka) salmon. The distribution of variability across the seven mtDNA segments differed substantially among species. Little similarity in the distribution of variable restriction sites was found even between the mitochondrial genomes of the even- and odd-year broodlines of pink salmon. Significantly different levels of nucleotide diversity were detected among three groups of genes: six NADH-dehydrogenase genes had the highest; two rRNA genes had the lowest; and a group that included genes for ATPase and cytochrome oxidase subunits, the cytochrome b gene, and the control region had intermediate levels of nucleotide diversity. Genealogies of mtDNA haplotypes were reconstructed for each species, based on the variation in all mtDNA segments. The contributions of variation within different segments to resolution of the genealogical trees were compared within each species. With the exception of sockeye salmon, restriction site data from different genome segments tended to produce rather different trees (and hence rather different genealogies). In the majority of cases, genealogical information in different segments of mitochondrial genome was additive rather than congruent. This finding has a relevance to phylogeographic studies of other organisms and emphasizes the importance of not relying on a limited segment of the mtDNA genome to derive a phylogeographic structure.

Animals↗
PubMedDate not supplied

Developmental constraints on an adaptive plasticity: reaction norms of pigmentation in adult segments of Drosophila melanogaster.

Variation of dark pigmentation according to developmental temperature was investigated in two geographic populations (France and India) with the isofemale line technique (20 lines for each population). The response curves called the reaction norms, were established in females for seven different segments: the mesothorax and abdomen segments 2-7 (Abd 2-7). In all cases the response curves were non-linear and had to be described either by a quadratic convex polynomial for thorax and Abd 2-5, or by a cubic polynomial for Abd 6 and 7. Among abdomen segments, increasing antero-posterior gradients were observed for several traits, including average pigmentation, overall phenotypic plasticity, the temperature of minimum pigmentation, and the curvature parameter of quadratic norms. Genetic correlations between abdomen segments were high when adjacent segments were considered, but became nil when more distant segments were correlated, suggesting that different pigmentation genes are expressed in the anterior and the posterior part of the abdomen. Characteristic values of reaction norms provided information either on trait value (i.e., the extension of pigmentation) or on plasticity. Correlations between plasticity and pigmentation were generally low and non-significant, suggesting their genetic independence. The overall darker pigmentation which is observed at low temperatures is assumed to be an adaptive plasticity. However, the differences which are evidenced among segments reveal strong interactions with developmental genes. These interactions are less likely to be a consequence of natural selection and are better interpreted as developmental constraints. The reaction norms analysis reveals the complexity of these interactions and should help, in the future, in the identification of the responsible thermosensitive genes.

Adaptation, Physiological↗
PubMedDate not supplied

Why are arthropods segmented?

Segmentation as an attribute of organisms is being increasingly discussed in the recent literature because (1) new phylogenies suggest that organisms classically considered to be segmented may lie in separate clades; (2) the molecular basis of segmental development has been much studied; (3) various theories of bilaterian origins place weight on segmentation as a primitive character; (4) there has been recent stress on the importance of modularity as an evolutionary topic. However, the definition and extent of segmentation are highly ambiguous and usually typological. Here, segmentation is regarded as an attribute of organs, not organisms. The evolution of just one system, the arthropod epidermis, is examined on the basis of the fossil record and the extant euarthropods, tardigrades, and onychophorans. It may be seen to have become segmented in a complex pathway that necessitated shifts in function, redundancy, and changes in associated organs. This complexity must inevitably reflect on, and to an extent have primacy over, the genetic basis for the changes involved. Evolutionary functional morphology has been relatively little considered in the context of the evolution of development, but may play an important role in defining the framework within which this evolution occurs.

Animals↗
PubMed2003

Spontaneous recovery of myocardial asynergic segments following acute myocardial infarction. The role of post-extrasystolic potentiation echocardiography in the predischarge evaluation.

AIMS: Predischarge identification of viable myocardium with a spontaneous recovery over time can be helpful in decision-making process following acute myocardial infarction (AMI). An intriguing hypothesis is that identification of viability in myocardial asynergic segments with or without spontaneous recovery over time may require an inotropic stimulus of a different intensity. To test this we used post-extrasystolic potentiation (PESP), which represents an inotropic stimulation of a different intensity as a function of coupling interval. METHODS AND RESULTS: Myocardial viability was assessed by PESP echocardiography in 86 patients with a first uncomplicated AMI. Spontenous changes in contractile function of viable but asynergic segments at predischarge were evaluated by a follow-up resting echocardiogram 1 month later. Viable myocardium of left ventricular asxynergic segments with spontaneous recovery or persistence of dysfunction showed its first significant improvement for different values of coupling interval during PESP (409+/-18 vs 336+/-23ms (milliseconds), P<0.0001). An arbitrary cut-off value for RR interval >or=380ms, correctly identified 91% of myocardial segments undergoing spontaneous recovery, while 99% of asynergic myocardial segments with spontaneous recovery had a threshold coupling interval >or=380ms. CONCLUSION: At predischarge following AMI, asynergic but viable myocardial segments by PESP with spontaneous recovery of contraction over time require an inotropic stimulus of lesser intensity to acutely improve contraction pattern than viable and asynergic segments without this favourable outcome.

Adult↗
PubMed2001

A real-time ST-segment monitoring algorithm for implantable devices.

Continuous ST-segment monitoring by implantable devices may lead to clarification of the substrate of arrhythmias, clarification of the origin of nonspecific chest pain, and titration or preventative application of established anti-ischemic therapies. Although ST-segment monitoring algorithms are available for surface electrocardiogram, the computational demand of algorithms for implantable devices must be minimized for considerations of device longevity. The new algorithm first locates a fiducial point (FPT) at the dominant peak of each QRS complex. The ST-segment deviation (measured at 2 rate-adaptive delays after FPT, eg, FPT + 96 ms and FPT + 152 ms at 60 BPM) with respect to the isoelectric level (measured at the minimum slope preceding the QRS) is then measured. The following features are also quantified by simple operations: R-R interval, R-wave slope, R-wave amplitude, ST-segment slope, and noise content during the isoelectric segment. Inconsistencies in these features relative to their adaptive normal ranges are used to reject noisy or ectopic beats and sudden morphology changes. Finally, the ST-segment deviation over time is filtered to reject rates of change that are not likely attributable to human ischemia. Performance of the algorithm was evaluated on the European Society of Cardiology ST-T Database, which contains 180 hours of ambulatory electrocardiogram with 250 expert-annotated ischemic episodes. The sensitivity was 79% [74% 84%] (mean [95% CI]) and positive predictivity was 81% [76% 86%]. This performance is statistically equivalent to that of published electrocardiogram algorithms that were validated on the same dataset. Estimates of computational burden suggest that the algorithm could process two channels of electrogram continuously for more than 5 years with current implanted device technology. In conclusion, we have developed an algorithm for ST-segment monitoring that can be implemented in current implantable devices with sensitivity and positive predictivity that are comparable with the state-of-the-art.

Algorithms↗
PubMed2002

ST-segment re-elevation unrelated to left ventricular ejection fraction or volume after anterior wall acute myocardial infarction treated with successful reperfusion.

Ventricular remodeling is a major determinant of the long-term prognosis of patients with acute myocardial infarction (AMI). No previous study examined the relation of ST-segment re-elevation to left ventricular (LV) volume and function in patients with successful reperfusion. We examined the relation of ST-segment re-elevation to LV function and volume indices in 51 patients with anterior wall AMI who underwent successful reperfusion by direct coronary angioplasty. A 12-lead electrocardiogram was recorded once a day until 7 days after the onset of AMI. ST-segment shift was measured and Sigma ST was defined as the sum of ST-segment elevation obtained from leads V2, V3, and V4. ST-segment re-elevation was defined as present when the difference between maximal and minimal Sigma ST (Delta ST) was >0.3mV. LV indices were obtained from left ventriculography performed approximately 1 month after the onset of AMI. ST-segment re-elevation was observed in 15 patients (29%). No significant differences were observed between the ST- re-elevation group and non-ST-re-elevation group in LV ejection fraction (49.4+/-14.0 vs. 51.2+/-11.5%), LV end-systolic volume index (35.8+/-13.1 vs. 33.8+/-12.5 mL/m(2)) or LV end-diastolic volume index (69.7+/-12.8 vs. 68.3+/-14.4 mL/m(2)). The difference between maximal and minimal Sigma ST (Delta ST) was not significantly correlated with any LV index examined. In conclusion, the present study revealed that ST-segment re-elevation after successful reperfusion in anterior wall AMI patients was not related to LV volume or function, indicating that ST-re-elevation is not a clinically meaningful indicator of LV remodeling.

Aged↗
PubMed2003

[Automatic classification of liver segments according to Couinaud: development of a new algorithm and evaluation spiral CT data].

PURPOSE: To develop a software tool that analyzes the anatomy of the portal vein branches and assigns segmental and subsegmental branches according to Couinaud's classification system and to evaluate its accuracy. MATERIALS AND METHODS: The algorithm was developed in C++ on a PC. The algorithm recognizes the three major branching patterns of the portal vein. Segmental and subsegmental branches are assigned to 8 segments following Couinaud and encoded by 8 colors. The software was evaluated using CT data sets of 39 patients. After the individual segmental anatomy of each patient was determined by an experienced radiologist, automatic classification was performed and the results were compared on a branch by branch basis. RESULTS: The numbering was accurate according to Couinaud's system in 358 of 409 segmental and subsegmental branches (88 %). The assignment failed in 51 of 409 branches due to unexpected anatomy or software problems. CONCLUSION: Automatic classification of portal vein branches and their appendant parenchyma is possible. The automatic designation of liver segments enables the three-dimensional visualization of the segmental anatomy. In the future, automatic analysis might facilitate the reporting and communication of CT findings.

Algorithms↗
PubMed2004

Evaluation of balanced steady-state free precession (TrueFISP) and K-space segmented gradient echo sequences for 3D coronary MR angiography with navigator gating at 3 Tesla.

PURPOSE: To test the feasibility of k-space segmented gradient-echo pulse sequences for free-breathing coronary magnetic resonance angiography (cMRA) on a clinical 3T system. MATERIALS AND METHODS: T2-prepared, fat-suppressed turbo field echo (TFE, turboFLASH, SFPGR) as well as balanced TFE (b-TFE, trueFISP, FIESTA, segmented SSFP) sequences with navigator gating for prospective motion correction were applied on a 3T system equipped with a six-element phased-array cardiac coil. In 15 healthy volunteers, the right coronary artery (RCA) was examined with TFE and b-TFE sequences. Due to examination time limitations, the left coronary artery (LM/LAD) was examined exclusively with the TFE sequence in ten volunteers. Image quality was graded on a five point scale (0 = not visualized to 4 = excellent). The length, diameter and sharpness of the vessels and the contrast-to-noise ratios (CNR) were measured. RESULTS: 98 % of all major segments (proximal/middle/distal) of the RCA could be seen with the TFE sequence and 82 % with the b-TFE sequence. The image quality for the three segments was graded higher for the TFE sequence (2.7/2.7/1.5) than for the b-TFE sequence (1.9/1.6/0.9) with P: (< or = 0.001/< or = 0.004/< or = 0.056). The kappa of the interobserver variability was 0.75 for the TFE sequence and 0.8 for the b-TFE sequence. The measured vessel lengths were longer for the TFE sequence (95 +/- 22 mm) than for the b-TFE sequence (80 +/- 40 mm; P < or = 0.115). No significant changes (P < or = 0.074, P < or = 0.145) in diameter and vessel sharpness of the RCAs were observed between the TFE (2.4 +/- 0.3 mm, 60 % +/- 5) and b-TFE sequences (2.4 +/- 0.3 mm, 62 % +/- 6). The CNR was higher for the TFE sequence (10.1 +/- 3.4) than for the b-TFE sequence (6.6 +/- 2.1; P < or = 0.014). All ten main and proximal segments of the LM/LAD, which were examined exclusively with the TFE sequence, were visible with grade 2.5 and 2.1. The middle segment was visible in seven cases with grade 1.3. In three cases, the distal segment was visible with grade 0.5. The vessel length was 78 +/- 27 mm and the CNR 11.9 +/- 2.4. CONCLUSION: The conventional TFE technique has demonstrated good feasibility for cMRA at 3T. In its operational availability at 3T, the b-TFE sequence is inferior to the TFE sequence.

Adult↗
PubMed1995

[Immunopathogenesis of allergic bronchial asthma. Detection of activated CD25-CD4 lymphocytes and release of cytokines in the bronchoalveolar space following segmental allergen challenge].

The aim of this study was to investigate the fundamental processes underlying the inflammatory response to allergen in mild non-symptomatic asthmatics, using a new model entailing endobronchial segmental provocation. Ten asymptomatic asthmatic volunteers (8 male, 2 female; mean age 28.2 [24-41] years) were challenged employing the segmental allergen provocation technique. 250 PNU in 5 ml 0.9% NaCl solution of either birch (n = 8) or grass (n = 2) pollen were instilled into one segment. As control, only the solvent was instilled into a segment of the contralateral lung. Bronchoalveolar lavage (BAL) with 100 ml prewarmed saline was performed 10 min and 18 h after allergen provocation. The cellular distribution and activation state in BAL fluid and peripheral blood was analysed by immunofluorescence and flow cytometry. The concentration of various cytokines was determined in the BAL fluid using ELISA and bioassays. In blood, segmental allergen provocation led to an increase both in numbers of neutrophils (3833 cells/microliters vs 6830 cells/microliters; P < 0.005) and activated IL-2R expressing (CD25+) CD4+ T cells (3.6% vs 4.8% of all CD4+ lymphocytes; P < 0.05). No change was observed in eosinophils and other leukocytes and lymphocyte subsets. In contrast, a significant 30-fold increase in eosinophils (0.39 x 10(6) vs 11.5 x 10(6) cells/100 ml; P < 0.01) and a twofold increase in CD25+ CD4+ T cells (P < 0.05) were found in BAL samples 18 h after segmental allergen challenge, when compared to the control segment. Analysis of the cytokine profile revealed significantly increased levels of several cytokines. Allergen challenge of extrinsic asthmatic subjects causes differentiation of activated CD25+ CD4+ lymphocytes which may contribute to the pathogenesis of the asthmatic inflammation through the release of various cytokines.

Adult↗
PubMed1985

Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer.

In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors less than or equal to 4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease-free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P less than 0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P less than 0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.

Breast Neoplasms↗
PubMed2000

Exercise-induced ST-segment depression and systolic dysfunction in patients with nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: ST-segment depression is common in patients with hypertrophic cardiomyopathy (HCM). However, it is not clear whether exercise-induced ST-segment depression in patients with HCM and patent coronary arteries is associated with changes in left ventricular function. METHODS: Left ventricular function was continuously evaluated in 53 patients with nonobstructive HCM during supine ergometer exercise with a radionuclide ventricular function monitor equipped with a cadmium telluride detector. On the basis of the ST-segment changes during exercise, the patients were divided into 2 groups: group N had no ST-segment depression, and group D had >/=0.1 mV ST-segment depression. RESULTS: Exercise duration, blood pressure, heart rate, and rate-pressure product during exercise did not differ between the 2 groups. End-diastolic volume at rest and at peak exercise did not differ between groups D and N. In contrast, the end-systolic volume in group N decreased during exercise, whereas in group D it increased. As a result, the left ventricular ejection fraction in group D decreased from 70% +/- 7% to 59% +/- 15% (P <.0001), whereas ejection fraction in group N increased from 65% +/- 8% to 71% +/- 11% (P =.0002). There was a strong correlation between exercise-induced ST-segment depression and changes in ejection fraction from rest to peak exercise (P <.0001). CONCLUSIONS: These results suggest that the exercise-induced ST-segment depression seen in patients with nonobstructive HCM is associated with systolic dysfunction during exercise.

Adolescent↗
PubMed2001

New method of on-line quantification of regional wall motion with automated segmental motion analysis.

We have recently developed an automated segmental motion analysis (A-SMA) system, based on an automatic "blood-tissue interface" detection technique, to provide real-time and on-line objective echocardiographic segmental wall motion analysis. To assess the feasibility of A-SMA in detecting regional left ventricular (LV) wall motion abnormalities, we performed 2-dimensional echocardiography with A-SMA in 13 healthy subjects, 22 patients with prior myocardial infarction (MI), and 9 with dilated cardiomyopathy (DCM). Midpapillary parasternal short-axis and apical 2- and 4-chamber views were obtained to clearly trace the blood-tissue interface. The LV cavity was then divided into 6 wedge-shaped segments by A-SMA. The area of each segment was calculated automatically throughout a cardiac cycle, and the area changes of each segment were displayed as bar graphs or time-area curves. The systolic fractional area change (FAC), peak ejection rate (PER), and filling rate (PFR) were also calculated with the use of A-SMA. In the control group, a uniform FAC was observed in real time among 6 segments in the short-axis view (60% +/- 10% to 78% +/- 9%), or among 5 segments in either the 2-chamber (59% +/- 12% to 75% +/- 16%) or 4-chamber view (58% +/- 13% to 72% +/- 12%). The variations of FAC, PER, and PFR were obviously decreased in infarct-related regions in the MI group and were globally decreased in the DCM group. We conclude that A-SMA is an objective and time-saving method for assessing regional wall motion abnormalities in real time. This method is a reliable new tool that provides on-line quantification of regional wall motion.

Adult↗
PubMed2007

Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination.

During the recombination of variable (V) and joining (J) gene segments at the T cell receptor alpha locus, a ValphaJalpha joint resulting from primary rearrangement can be replaced by subsequent rounds of secondary rearrangement that use progressively more 5' Valpha segments and progressively more 3' Jalpha segments. To understand the mechanisms that target secondary T cell receptor alpha recombination, we studied the behavior of a T cell receptor alpha allele (HYalpha) engineered to mimic a natural primary rearrangement of TRAV17 to Jalpha57. The introduced ValphaJalpha segment was shown to provide chromatin accessibility to Jalpha segments situated within several kilobases downstream and to suppress germ-line Jalpha promoter activity and accessibility at greater distances. As a consequence, the ValphaJalpha segment directed secondary recombination events to a subset of Jalpha segments immediately downstream from the primary rearrangement. The data provide the mechanistic basis for a model of primary and secondary T cell receptor alpha recombination in which recombination events progress in multiple small steps down the Jalpha array.

Alleles↗