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Results for “Heterogeneity Mapping”

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PubMed2005

Using concept maps to optimize the composition of collaborative student groups: a pilot study.

AIM: The aim of this paper is to stimulate interest in the practical classroom application of concept mapping strategies as an approach that teachers can easily use to enhance collaborative learning. BACKGROUND: Concept mapping has been developed as a tool to support meaningful learning. However, much of the research literature fails to explain how concept maps might be most gainfully employed within the classroom. As a result, concept mapping is a tool that is under-used. METHODS: Students on a postgraduate teacher preparation programme for nurses were arranged in triads on the basis of the morphology of individually-produced concept maps for the topics of 'genetics' and 'pathogenic microbes'. They were arranged in heterogeneous triads to produce a consensus map for 'pathogenic microbes', and then in homogeneous triads to produce a consensus map for 'genetics'. The number of acceptable propositions found in their individual maps was compared with the number found in the consensus group maps, and gain scores were calculated for each participant. FINDINGS: Participants arranged in triads of individuals having very different knowledge structures were found to make a greater improvement than those arranged in triads composed of individuals with qualitatively similar knowledge structures. CONCLUSIONS: The study was undertaken with a very small sample and only looked at two topic areas. However, the findings support the idea that collaborative groups work most effectively when individuals within the group bring different perspectives to a problem, and that this perspective can be usefully identified within the classroom environment as variations in concept map morphology.

Concept Formation↗

PubMed1993

Genetic and antigenic analyses of influenza A (H1N1) viruses, 1986-1991.

Eighteen strains of human influenza A (H1N1) viruses isolated between August 1986 and January 1991 were analyzed in this study. Examination of the total viral genome of 12 strains by T1 mapping revealed that considerable genetic heterogeneity exists among these viruses. Partial sequencing of each of the non-HA RNA segments of 4 viruses having divergent T1 oligonucleotide maps indicated that only one was a reassortant virus that had genes from both the influenza A (H1N1) and (H3N2) subtypes. This reassortant obtained its PB2 gene from a virus of the H3N2 subtype and the other 7 RNA segments from an H1N1 parent. Sequencing studies of the HA1 domains of the hemagglutinin (HA) genes of these 18 strains revealed that although these viruses are antigenically similar to the reference strains A/Taiwan/1/86 and A/Singapore/6/86, 7 conserved amino acid substitutions that are shared by recently isolated H1N1 viruses have occurred in the main stream of evolution of the H1N1 subtype. Our data indicate that: (1) Genetic reassortment continues to contribute to genetic variability of H1N1 viruses. (2) Genetic variants of non-reassortant H1N1 viruses are co-circulating in the world. (3) The HA's of recent H1N1 viruses are related to those of the 1986 reference strains. (4) Although there has been little detectable antigenic variability, the HA genes of human epidemic influenza A (H1N1) viruses have continued to evolve at an evolutionary rate similar to that for the H1N1 and H3N2 viruses analyzed previously.

Amino Acid Sequence↗

PubMed2026

Exploring genomic regions regulating the liver transcriptome and energy homeostasis in pigs.

In pigs, energy homeostasis has an impact on meat quality and health. In a Duroc pig population, 30 quantitative trait locus (QTL) regions associated with fatty acid (FA) composition in adipose tissue, plasma, liver and muscle were previously identified. Mapping of expression quantitative trait locus (eQTL) regions will provide a molecular hypothesis for genotype-phenotype interactions and may allow the identification of shared causal variants, key to increasing our understanding of the genetic regulation of FA composition and energy homeostasis. However, gene expression is impacted by environmental factors, while individual-level allelic imbalance (AI) can be more reliable and can be surveyed via allelic-specific expression (ASE) analysis. Furthermore, treatment of ASE as a quantitative trait allows the identification of allele-specific expression quantitative trait loci (aseQTLs), which are variants whose heterozygosity is linked to the AI of a nearby single-nucleotide polymorphism (SNP), pointing to regulatory elements. In this study, liver was selected as a key metabolic hub with an important role in the regulation of energy homeostasis, and 310 liver RNA sequencing samples were analysed using a combination of (1) eQTL mapping, (2) ASE analysis, and (3) aseQTL mapping methods. A total of 2 188 eQTL regions were identified, mostly cis-eQTL regions (73.17%). ASE analysis reported 1 964 ASE SNPs, associated with 633 genes. Finally, aseQTL mapping reported 64 172 aseQTL, associated with the AI of 31 genes. Colocalisation analysis combined with ASE analysis showed that the expression of FADS1 and FADS2 genes is associated with the polyunsaturated FA composition in several tissues, where microRNA regulation may be present. Finally, in the DGAT2 gene, annotated in a QTL region associated with multiple FAs in adipose tissue, ASE revealed allelic imbalance in the 3' untranslated region (UTR) of this gene. Allelic differential expression can be caused by a 13-bp insertion affecting messenger RNA stability, previously described, exemplifying how allelic imbalance is caused by a post-transcriptional regulatory mechanism undetectable by eQTL mapping. Furthermore, aseQTLs were associated with this gene, linked to a previously identified copy number variant not yet associated with DGAT2 expression. These results demonstrate how ASE analysis and aseQTL mapping can complement eQTL mapping, as they resolved a complex region affected by allelic heterogeneity, a main confounding effect of QTL mapping. In conclusion, the combination of eQTL mapping, ASE analysis and aseQTL mapping allowed the characterisation of the regulation of liver gene expression, improving our understanding of the genetic determinism of energy homeostasis.

Allele-specific expression↗

PubMed2005

Evidence of a genetic heterogeneity of familial hydatidiform moles.

We previously mapped a maternal recessive locus responsible for familial hydatidiform moles (HMs) to 19q13.4. The candidate region has recently been narrowed down to 1.1 megabases. Here, we report the segregation of alleles at 18 genetic markers, including nine new ones, from the HMs candidate region in a recently reported consanguineous family. In this family, five affected women had a total of seven HMs, three miscarriages, and three normal children. Linkage and haplotype analyses exclude linkage to 19q13.4 and indicate the presence of a second recessive locus responsible for familial molar pregnancies. The heterogeneity in the phenotype of the conceptuses of patients with familial HMs is in agreement with previous observations and seems to be a common feature of this condition. This indicates that the homozygous genetic defects leading to hydatidiform moles can be modulated by other genetic or environmental factors. The identification of these factors may unravel natural ways to treat these forms of reproductive wastage and reverse the infertility of women with recurrent moles.

Adult↗

PubMed2001

The ontogeny of the homing pigeon navigational map: evidence for a sensitive learning period.

Homing pigeons can learn a navigational map by relying on the heterogeneous distribution of atmospheric odours in the environment. To test whether there might be a sensitive period for learning an olfactory-based navigational map, we maintained a group of young pigeons in an aviary screened from the winds until the age of three to four months post-fledging. Subsequently, the screens were removed and the pigeons were exposed to the winds and the environmental odours they carry for three months. One control group of pigeons was held in a similar aviary but exposed to the winds immediately upon Hedging, while another control group of pigeons was allowed free-flight. When the pigeons from the three groups were released from two distant release sites at about six months of age post-fledging, the two control groups were found to be equally good at orientating and returning home, while the experimental pigeons held in the shielded aviary for the first three months post-fledging were unable to orientate homeward and they were generally unsuccessful in returning home. This result supports the hypothesis that environmental experience during the first three months post-fledging is critical for some aspect of navigational map learning and that navigational map learning displays sensitive period-like properties.

Animals↗

PubMed2004

Prospects for admixture mapping of complex traits.

Admixture mapping extends to human populations the principles that underlie linkage analysis of an experimental cross. For detecting genes that contribute to ethnic variation in disease risk, admixture mapping has greater statistical power than family-linkage studies. In comparison with association studies, admixture mapping requires far fewer markers to search the genome and is less affected by allelic heterogeneity. Statistical-analysis programs for admixture mapping are now available, and a genomewide panel of markers for admixture mapping in populations formed by West African-European admixture has been assembled. Some of the remaining technical challenges include the ability to ensure that the statistical methods are robust and to develop marker panels for other admixed populations. Where admixed populations and panels of markers informative for ancestry are available, admixture mapping can be applied to localize genes that contribute to ethnic variation in any measurable trait.

Black People↗

PubMed1996

Genetic mapping of quantitative trait loci controlling growth and wood quality traits in Eucalyptus grandis using a maternal half-sib family and RAPD markers.

Quantitative trait loci (QTL) mapping of forest productivity traits was performed using an open pollinated half-sib family of Eucalyptus grandis. For volume growth, a sequential QTL mapping approach was applied using bulk segregant analysis (BSA), selective genotyping (SG) and cosegregation analysis (CSA). Despite the low heritability of this trait and the heterogeneous genetic background employed for mapping, BSA detected one putative QTL and SG two out of the three later found by CSA. The three putative QTL for volume growth were found to control 13.7% of the phenotypic variation, corresponding to an estimated 43.7% of the genetic variation. For wood specific gravity five QTL were identified controlling 24.7% of the phenotypic variation corresponding to 49% of the genetic variation. Overlapping QTL for CBH, WSG and percentage dry weight of bark were observed. A significant case of digenic epistasis was found, involving unlinked QTL for volume. Our results demonstrate the applicability of the within half-sib design for QTL mapping in forest trees and indicate the existence of major genes involved in the expression of economically important traits related to forest productivity in Eucalyptus grandis. These findings have important implications for marker-assisted tree breeding.

Chromosome Mapping↗

PubMed2000

Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping.

Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.

Adolescent↗

PubMed2000

Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas.

BACKGROUND AND PURPOSE: Elevated relative regional cerebral blood volume (rCBV) reflects the increased microvascularity that is associated with brain tumors. The purpose of this study was to investigate the potential role of rCBV in the determination of recurrent/residual disease in patients with treated gliomas. METHODS: Thirty-one rCBV studies were performed in 19 patients with treated gliomas. All patients also had proton MR spectroscopy and conventional MR imaging. Regions of abnormality were identified on conventional MR images by two neuroradiologists and compared with rCBV and MR spectroscopic data. Metabolites and rCBV were quantified and compared in abnormal regions. RESULTS: In high-grade tumors, rCBV values were proportional to choline in regions of tumor and nonviable tissue. Although the presence of residual/recurrent disease was often ambiguous on conventional MR images, the rCBV maps indicated regions of elevated vascularity in all low-grade tumors and in 12 of 17 grade IV lesions. Regions of elevated and low rCBV corresponded well with spectra, indicating tumor and nonviable tissue, respectively. CONCLUSION: This study suggests that rCBV maps and MR spectroscopy are complementary techniques that may improve the detection of residual/recurrent tumor in patients with treated gliomas. Compared with the spectra, the rCBV maps may better reflect the heterogeneity of the tumor regions because of their higher resolution. The multiple markers of MR spectroscopy enable better discrimination between normal and abnormal tissue than do the rCBV maps.

Adult↗

PubMed2006

RLS3: fine-mapping of an autosomal dominant locus in a family with intrafamilial heterogeneity.

A new locus for restless legs syndrome (RLS3) was identified on chromosome 9p24-22. The authors analyzed transmission disequilibrium tests (TDTs) and affecteds-only linkage analysis in one large family of Bavarian origin, taking into account age at onset. P values were 0.0054 for marker D9S1810 for TDT and 0.0009 for the affecteds-only linkage analysis, providing a confirmation of RLS3. This study narrows the region containing the autosomal dominant RLS3 locus to 11.1 cM (16.6 Mbp).

Chromosome Disorders↗

PubMed1989

In situ localization of microtubule-associated protein mRNA in the developing and adult rat brain.

We have used cDNA probes specific for three of the major brain microtubule-associated proteins (MAPs), MAP1, MAP2, and MAP5, to study the timing of appearance, relative abundance, and intracellular compartmentalization of MAP gene transcripts in developing rat brain. The MAP1 probe hybridizes throughout the brain, in both grey and white matter. MAP2 mRNA is detected only in grey matter and appears in cerebral neurons only after they have ceased dividing and have migrated to the cortical plate. The MAP5 cDNA hybridizes throughout the embryonic brain, but by P12, MAP5 mRNA distribution is restricted to relatively immature areas. MAP2 mRNA, found in dendrites in the developing brain, persists in some adult dendrites. MAP5 mRNA, like beta-tubulin mRNA, is found only in the cell bodies of developing neurons, indicating that the protein must be transported from the soma into processes. MAP1 mRNA is found only in the proximal regions of cortical pyramidal cell dendrites in both developing and adult brain. The diverse distributions of MAP gene transcripts emphasize the importance of these proteins in generating heterogeneity of microtubule function and indicate that MAP compartmentalization within neurons is regulated in part by differential mRNA transport.

Aging↗

PubMed1995

Presence and regulation of Raf-1-K (Kinase), MAPK-K, MAP-K, and S6-K in rat nephron segments.

Renal nephron segments are heterogeneous, and receptors for endothelin (ET)-1, ET-3, Angiotensin II (AII), epidermal growth factor (EGF), and insulin-like growth factor I distribute differently along the nephron segments. Recently, growth factors and vasoactive substances are reported to stimulate mitogen-activated protein kinase (MAP-K). In this study, we showed that mRNA and proteins of MEK-K, Raf-1-K, MAPK-K, MAP-K (p42 and p44), and S6-K are expressed ubiquitously in intact nephron segment. We demonstrated that four tiers of a cascade composed of the Raf-1-K, MAP-K, MAP-K, and S6-K are stimulated by ET-1 and ET-3 in rat intact glomeruli (Glm) via primarily B-type ET receptors and PKC. The stimulatory effect of EGF and IGF-I to MAP-K activity is inhibited by a tyrosine kinase inhibitor in Glm. IGF-I significantly stimulates MAP-K activity and EGF and All moderately stimulate MAP-K activity in the proximal convoluted tubule (PCT). EGF significantly increased MAP-K cascades and ET-1 and ET-3 slightly increased MAP-K cascades in the medullary thick ascending limb (MTAL). EGF significantly stimulated MAP-K cascades, and ET-1 and ET-3 moderately stimulate MAP-K cascades in the outer medullary collecting duct (OMCD) and the inner medullary collecting duct (IMCD). MAPK-K and S6-K are similarly stimulated by these agonists in each segment. This study shows that MAP-K cascades are expressed in every nephron segment. ET-1, ET-3, All, EGF, and IGF-I stimulate MAP-K cascades heterogeneously along the nephron segment. It was concluded that MAP-K cascades play an important role in the regulation of renal function.

Animals↗

PubMed2004

FTIR imaging of wheat endosperm cell walls in situ reveals compositional and architectural heterogeneity related to grain hardness.

Endosperm cell walls of cultivars of wheat (Triticum aestivum L.) selected for their endosperm texture (two soft and two hard) were analysed in situ by Fourier transform infrared (FTIR) microspectroscopy. FTIR imaging coupled with statistical analysis was used to map the compositional and structural heterogeneity within transverse sections from which cell contents had been removed by sonication. In the majority of grains analysed, two distinct populations of endosperm cells could be identified by spectral features that were related to cell morphology and age, regardless of cultivar. The main cell-wall component responsible for these differences was the polysaccharide arabinoxylan. In a few samples, this heterogeneity was absent, for reasons that are not understood, but this was not correlated to endosperm texture or growth conditions. Within the same population of endosperm cells, cell walls of hard endosperm could be distinguished from those of soft endosperm by their spectral features. Compared to hard cultivars, the peripheral endosperm of soft cultivars was characterised by a higher amount of polymer, whose spectral feature was similar to water-extractable arabinoxylan. In contrast, no specific compound has been identified in the central endosperm: structural differences within the polysaccharides probably contribute to the distinction between hard and soft cultivars. In developing grain, a clear difference in the composition of the endosperm cell walls of hard and soft wheat cultivars was observed as early as 15 days after anthesis.

Cell Wall↗

PubMed1990

Comparative analysis of vaccinia virus promoter activity in fowlpox and vaccinia virus recombinants.

A quantitative and qualitative comparison of vaccinia virus (VV) promoter activity in fowlpox virus (FPV) and VV recombinants was performed. The VV PL11 late promoter was used to express beta-galactosidase from the E. coli LacZ gene in FPV (FPV-LacZ) and VV (VV-LacZ) recombinants. Time courses of FPV-LacZ beta-galactosidase expression in chicken embryo skin (CES) cells demonstrated temporal regulation of the PL11 promoter with maximum enzyme activity nine- and four-fold lower than those obtained in VV-LacZ infected 143B and CES cells, respectively. The level of beta-galactosidase activity per LacZ DNA gene copy was determined for each recombinant and found to be greater for VV-LacZ than FPV-LacZ. The VV P7.5 early/late promoter was used to express the E. coli xanthine-guanine phosphoribosyl transferase (Ecogpt) gene in FPV and VV recombinants. Northern blot analysis showed early Ecogpt RNA transcripts to be of defined lengths. Transcript size estimations mapped the termination sites to regions containing sequences associated with VV early transcript termination, providing supportive evidence for a common poxvirus early transcript termination signal. Late LacZ and Ecogpt transcripts were heterogeneous in length. S1 nuclease mapping of the 5'-ends of early and late Ecogpt RNA transcripts produced by FPV and VV recombinants showed transcription initiation occurred at the same sites in both poxviruses and corresponded to the regions previously identified as the early and late start sites of the P7.5 promoter. These results would indicate a high level of conservation in the expression and regulation of genes by poxviruses.

Animals↗

PubMed1998

Epitope mapping of human centromere autoantigen centromere protein C (CENP-C); heterogeneity of anti-CENP-C response in rheumatic diseases.

OBJECTIVE: To analyze the autoantigenic epitopes of centromere protein C (CENP-C) recognized by anti-centromere antibodies (ACA). METHODS: A series of truncated peptides of human CENP-C were expressed in Escherichia coli and immunoblotting analysis was performed with 45 ACA positive sera obtained from patients with different types of autoimmune diseases. RESULTS: Although 9 epitopes were scattered over the entire molecule, the N terminus was immunodominant for IgG and IgM classes and the C terminus was dominant for IgG class. Both epitopes were separately located within the instability and centromere targeting domains in vivo, or the oligomerization-accessible and homodimerization domains in vitro, respectively. In contrast, minor epitopes were clustered at the internal DNA binding domain. A number of patterns of immunoreactivities against 3 representative antigenic sites by IgG or IgM class antibodies were found. CONCLUSION: The results indicated the existence of different anti-CENP-C responses in rheumatic diseases and a possible correlation between antigenic regions and functional sites in the CENP-C antigen.

Autoantigens↗

PubMed1988

Epitope mapping with a recombinant human 68-kDa (U1) ribonucleoprotein antigen reveals heterogeneous autoantibody profiles in human autoimmune sera.

Several cDNA fragments encoding parts of the (U1)RNP specific 68-kDa autoantigen were expressed in Escherichia coli and the fusion proteins were used as substrate for localization of the autoreactive epitopes. We have identified a region of approximately 30 amino acids reacting with more than 90% (16 of 17) of all human anti-p68 sera tested, regions which carry only a few and a region with no autoepitopes. Comparative analysis of epitopes recognized on partially degraded fusion proteins indicated that the anti-p68 autoimmune response is polyclonal. It involves generation of antibodies to several epitopes including one in a region with retroviral gag protein homology speculated to play a role in the initiation of the autoimmune response. Each of the 17 sera tested contained a different set of autoantibody specificities. These data are not consistent with random mutation as a sole mechanism of anti-p68 autoantibody induction and argue for an Ag-driven autoimmune response.

Antibodies, Antinuclear↗

PubMed2005

Three-dimensional recovery time dispersion map by 64-channel magnetocardiography may demonstrate the location of a myocardial injury and heterogeneity of repolarization.

BACKGROUND: QT dispersion reveals heterogeneities in the repolarization time in the three-dimensional (3D) structure of the ventricular myocardium. In this study, we report on a 3D function map of recovery time (RT) dispersions as measured by 64-channel magnetocardiography (MCG). METHODS: MCG were simultaneously recorded in 29 controls and 21 patients with previous myocardial infarction (MI). The 3D current density was calculated from 64-channel MCG data in the Bz component using a space filter. The heart outline, reconstructed from the integrated the current density, revealed both the atrium and ventricle. The RT for the intervals between QRS onset and the time of the maximum dT/dt of T wave, and the peak to the end of the T wave (T(peak)-negative dT/dt) were automatically measured by means of a computer from 3D MCG data. The corrected RT (RTc) and corrected T(peak)-negative dT/dt were then calculated using Bazett's formula. The 3D RTc and the corrected T(peak)-negative dT/dt dispersion map were superimposed on the heart outline generated by MCG. RESULTS: The RTc was significantly longer for the MI group than in the control group (67+/-25 ms1/2 vs. 16+/-6 ms1/2) (p<0.0001). The corrected T(peak)-negative dT/dt dispersions in each patient was also significantly longer for the MI group than in the control group (35+/-27 ms1/2 vs. 10+/-5 ms1/2) (p<0.0001). Furthermore, the 3D RTc and T(peak)-negative dT/dt dispersion maps corresponded with the space location of MI, as defined by Tc-99m tetrofosmin myocardial imaging CONCLUSIONS: 3D RTc and T(peak)-negative dT/dt dispersion maps in the ST segment, obtained by 64-channel MCG may be used demonstrate the location of a myocardial injury and heterogeneities of repolarization.

Adult↗

PubMed2000

New quantitative methods of ventricular repolarization analysis in patients with left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is accompanied by specific changes in ventricular electrophysiology, which are potentially arrhythmogenic. Nevertheless, the electrocardiographic diagnostic signs for LVH have a relatively low predictive power for arrhythmic events and sudden death. We thought that other parameters derived from the surface ECG, not apparent at visual inspection, might be detected by specific analysis of electrocardiographic digital recordings. The purpose of our work was to analyze the surface distribution of repolarization potentials and search for subtle alterations not revealed by the usual electrocardiographic processing, which are likely to reflect ventricular repolarization heterogeneity. METHODS: Body surface potential maps were recorded from 62 chest leads in 16 patients with LVH due to aortic stenosis and in 35 normal subjects. By applying a principal component analysis of the ST-T waves, we computed the similarity index. The value of the similarity index is inversely proportional to the variability of T wave morphology and a low value is considered a marker of repolarization heterogeneity. RESULTS: The similarity index was significantly lower in LVH patients than in normals both in 62 leads (0.73 +/- 0.067 vs 0.77 +/- 0.044, p = 0.03) and in 12 unipolar leads (V1- V8, V3R, VR, VL, VF) extracted from the map (0.77 +/- 0.075 vs 0.81 +/- 0.045, p = 0.03). Moreover, we computed the "late repolarization deviation index", which quantifies the instantaneous variations of surface potential distribution from peak to end of the T wave. This index was significantly higher in LVH patients than in controls (in 62 leads 0.07 +/- 0.05 vs 0.028 +/- 0.016, p = 0.005; in 12 leads 0.064 +/- 0.052 vs 0.024 +/- 0.020, p = 0.008). CONCLUSIONS: The values of similarity index and of late repolarization deviation index found in LVH patients suggest a higher than normal degree of repolarization heterogeneity, not detected by the usual electrocardiographic analysis. Since both indices maintained statistical significance when calculated on the 12 leads derived from our map lead system, they could be reliably computed from digital recordings of the 12 conventional leads.

Adult↗