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PubMed2003

Microtubule-associated epithelial protein E-MAP-115 is localized in the spermatid manchette.

A microtubule-associated protein E-MAP-115 has been originally isolated and characterized from HeLa cells. Because of its predominant expression in cultured cells of epithelial origin, it has been suggested to be involved in the regulation of cell polarization. The present immunocytochemical, Northern blot and in situ hybridization analysis of E-MAP-115 in the mouse and rat seminiferous epithelium indicates its distinct association with the spermatid manchette, a unique microtubular structure which appears in the cytoplasm of spermatids at step 8 when nuclear polarization and elongation starts. At steps 15-16 when manchette has been disassembled, immunoreactivity for E-MAP-115 disappeared. At immunoelectron microscopical level, E-MAP-15 was associated with the microtubules of the manchette. In the Western and Northern blot analysis, a distinct stage-dependent expression of a single E-MAP-115 polypeptide and two mRNA species (3.4 and 2.4 kb) could be identified. MTEST 60, a spermatid-specific transcript, showed a 100% homology over region of 68-193 bp of E-MAP-115 sequence. The reported specific localization of E-MAP-115 to the spermatid manchette strongly supports its role as a regulator of cell polarization. This, in turn, supports the hypotheses concerning the dynamic function of the manchette during spermiogenesis.

Animals↗
PubMed1997

Changes in brain function after manipulation of the cervical spine.

OBJECTIVE: To ascertain whether manipulation of the cervical spine is associated with changes in brain function. DESIGN: Physiological cortical maps were used as an integer of brain activity before and after manipulation of the cervical spine in a large (500 subjects), double-blind controlled study. SETTING: Institutional clinic Participants: Adult volunteers. INTERVENTION: Five hundred subjects were divided into six comparative groups and underwent specific manipulation of the second cervical motion segment. Blinded examiners obtained reproducible pre- and postmanipulative cortical maps, which were subjected to statistical analysis. MAIN OUTCOME MEASURES: Brain activity was demonstrated by reproducible circumferential measurements of cortical hemispheric blind-spot maps before and after manipulation of the second cervical motion segment. Twelve null hypotheses were developed. The critical alpha level was adjusted in accordance with Bonferroni's theorem to .004 (.05 divided by 12) to reduce the likelihood of wrongly rejecting the null hypothesis (i.e., committing a Type I error). RESULTS: Manipulation of the cervical spine on the side of an enlarged cortical map is associated with increased contralateral cortical activity with strong statistical significance (p < .001). Manipulation of the cervical spine on the side opposite an enlarged cortical map is associated with decreased cortical activity with strong statistical significance (p < .001). Manipulation of the cervical spine was specific for changes in only one cortical hemisphere with strong statistical significance (p < .001). CONCLUSIONS: Accurate reproducible maps of cortical responses can be used to measure the neurological consequences of spinal joint manipulation. Cervical manipulation activates specific neurological pathways. Manipulation of the cervical spine may be associated with an increase or a decrease in brain function depending upon the side of the manipulation and the cortical hemisphericity of a patient.

Adult↗
PubMed1988

Characterization of insulin-stimulated microtubule-associated protein kinase. Rapid isolation and stabilization of a novel serine/threonine kinase from 3T3-L1 cells.

A protein kinase, termed microtubule-associated protein (MAP) kinase, which phosphorylates microtubule-associated protein 2 (MAP-2) in vitro and is stimulated 1.5-3-fold in extracts from insulin-treated 3T3-L1 cells has been identified (Ray, L.B., and Sturgill, T.W. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1502-1506). Here, we describe chromatographic properties of MAP kinase and provide biochemical characterization of the partially purified enzyme. Isolation of the enzyme is facilitated by its unusually high affinity for hydrophobic interaction chromatography matrices. The molecular weight of the partially purified enzyme was determined to be 35,000 by gel filtration chromatography and 37,000 by glycerol gradient centrifugation. MAP kinase activity of chromatographic fractions correlated precisely with the presence of a 40-kDa phosphoprotein detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. MAP kinase has a Km of 7 microM for ATP and does not utilize GTP. Acetyl-CoA carboxylase, ATP citrate-lyase, casein, histones, phosvitin, protamine, and ribosomal protein S6 were all poor substrates relative to MAP-2. The enzyme is inhibited by fluoride and beta-glycerol phosphate but not by heparin. These properties of MAP kinase distinguish it from protein kinases previously described in the literature.

Animals↗
PubMed2000

Microtubule binding of the drosophila DMAP-85 protein is regulated by phosphorylation in vitro.

The phosphorylation of microtubule-associated proteins (MAPs) is thought to be a key factor in the regulation of microtubule (MT) stability. Previously we isolated DMAP-85, a Drosophila MAP shown to be associated with stable MTs. In this work we show that DMAP-85 phosphorylated in cell-free early embryo extracts is released from MTs. MPM-2 antibodies recognize the phosphorylated protein. In vitro, DMAP-85 can be phosphorylated by the mitotic kinase Polo affecting its binding to MTs and creating MPM-2 epitopes on the protein. The results suggest that phosphorylation of DMAP-85 might affect its MT stabilizing activity during early mitotic cycles.

Animals↗
PubMed2006

Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. RESULTS: Over 500,000 public bovine expressed sequence tagged (EST) sequences were used to search for coding SNPs (cSNPs). A total of 15,353 SNPs were detected in the transcribed sequences studied, of which 6,325 were predicted to be coding SNPs with the remaining 9,028 SNPs presumed to be in untranslated regions. Of the cSNPs detected, 2,868 were predicted to result in a change in the amino acid encoded. In order to determine the actual number of non-synonymous polymorphic SNPs we designed assays for 920 of the putative SNPs. These SNPs were then genotyped through a panel of cattle DNA pools using chip-based MALDI-TOF mass spectrometry. Of the SNPs tested, 29% were found to be polymorphic with a minor allele frequency >10%. A subset of the SNPs was genotyped through animal resources in order to look for association with age of puberty, facial eczema resistance or meat yield. Three SNPs were nominally associated with resistance to the disease facial eczema (P < 0.01). CONCLUSION: We have identified 15,353 putative SNPs in or close to bovine genes and 2,868 of these SNPs were predicted to be non-synonymous. Approximately 29% of the non-synonymous SNPs were polymorphic and common with a minor allele frequency >10%. Of the SNPs detected in this study, 99% have not been previously reported. These novel SNPs will be useful for association studies or gene mapping.

Amino Acid Substitution↗
PubMed2005

Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases.

BACKGROUND: Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. METHODS AND RESULTS: In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases (P = 0.006) and earlier age of onset (P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases (P = 0.01) and tumor size (P = 0.01). CONCLUSION: Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity.

Journal Article↗
PubMed2005

Radial compression of microtubules and the mechanism of action of taxol and associated proteins.

Microtubules (MTs) are hollow cylindrical polymers composed of alphabeta-tubulin heterodimers that align head-to-tail in the MT wall, forming linear protofilaments that interact laterally. We introduce a probe of the interprotofilament interactions within MTs and show that this technique gives insight into the mechanisms by which MT-associated proteins (MAPs) and taxol stabilize MTs. In addition, we present further measurements of the mechanical properties of MT walls, MT-MT interactions, and the entry of polymers into the MT lumen. These results are obtained from a synchrotron small angle x-ray diffraction (SAXRD) study of MTs under osmotic stress. Above a critical osmotic pressure, P(cr), we observe rectangular bundles of MTs whose cross sections have buckled to a noncircular shape; further increases in pressure continue to distort MTs elastically. The P(cr) of approximately 600 Pa provides, for the first time, a measure of the bending modulus of the interprotofilament bond within an MT. The presence of neuronal MAPs greatly increases P(cr), whereas surprisingly, the cancer chemotherapeutic drug taxol, which suppresses MT dynamics and inhibits MT depolymerization, does not affect the interprotofilament interactions. This SAXRD-osmotic stress technique, which has enabled measurements of the mechanical properties of MTs, should find broad application for studying interactions between MTs and of MTs with MAPs and MT-associated drugs.

Animals↗
PubMed1992

Cloning and mapping of telomere-associated sequences from Hordeum vulgare L.

We present a novel approach to the efficient cloning of telomere-associated sequences and demonstrate its application to the cloning and mapping of these sequences from barley. The method is a modification of the Vectorette PCR technique and allows specific amplification and cloning of subtelomeric sequences. Telomere-associated sequences isolated from barley include hypervariable, repetitive sequences. Polymorphisms detected by subtelomeric markers behaved as Mendelian factors and were mapped to the most distal positions of barley chromosomes 1, 2, and 4.

Base Sequence↗
PubMed2005

Factors affecting statistical power in the detection of genetic association.

The mapping of disease genes to specific loci has received a great deal of attention in the last decade, and many advances in therapeutics have resulted. Here we review family-based and population-based methods for association analysis. We define the factors that determine statistical power and show how study design and analysis should be designed to maximize the probability of localizing disease genes.

Data Interpretation, Statistical↗
PubMed1988

High molecular weight microtubule-associated proteins bind to actin lattices (Hirano bodies).

Hirano bodies are filamentous, paracrystalline inclusions that are found in dendrites and cell bodies of neurons in Alzheimer's and other neurodegenerative diseases. Actin appears to be a major component of these structures. We present evidence that tropomyosin and high molecular weight microtubule-associated proteins (MAPs) are also components of Hirano bodies. Although an association between actin and MAPs has been noted in vitro, interactions in vivo have not heretofore been demonstrated. Since microtubules are not present in Hirano bodies, and anti-tubulin and anti-neurofilament antibodies do not bind to Hirano bodies, the association between MAPs and these inclusions is likely a result of interactions between MAPs and actin, and not MAPs and microtubules or neurofilaments.

Actins↗
PubMed2002

Novel linkage mapping approach using DNA pooling in human and animal genetics. I. Detection of complex disease loci.

DNA pooling is a potential methodology for genetic loci with small effect contributing to complex diseases and quantitative traits. This is accomplished by the rapid preliminary screening of the genome for the allelic association with the most common class of polymorphic short tandem repeat markers. The methodology assumes as a common founder for the linked disease locus of interest and searches for a region of a chromosome shared between affected individuals. The general theory of DNA pooling basically relies on the observed differences in the allelic distribution between pools from affected and unaffected individuals, including a reduction in the number of alleles in the affected pool, which indicate the sharing of a chromosomal region. The power of statistic for associated linkage mapping can be determined using two recently developed strategies, firstly, by measuring the differences of allelic image patterns produced by two DNA pools of extreme character and secondly, by measuring total allele content differences by comparing between two pools containing large numbers of DNA samples. These strategies have effectively been utilized to identify the shared chromosomal regions for linkage studies and to investigate the candidate disease loci for fine structure gene mapping using allelic association. This paper outlines the utilization of DNA pooling as a potential tool to locate the complex disease loci, statistical methods for accurate estimates of allelic frequencies from DNA pools, its advantages, drawbacks and significance in associate linkage mapping using pooled DNA samples.

Animals↗
PubMed1991

Latent learning in a swimming pool place task by rats: evidence for the use of associative and not cognitive mapping processes.

Using a latent learning paradigm, the experiments examine two hypotheses of how rats solve place navigation tasks. According to associative theory, experience with all relevant cues is required for accurate navigation. According to cognitive mapping theory, animals can generate novel trajectories from knowledge of spatial relations of objects in the environment. Rats that had been placed on a platform, which was submerged in a pool of opaque water and was moved each day, were tested later for their ability to find the platform using only surrounding room cues. One 30-sec exposure to a platform location was effective in improving performance. Improvement was greatest when tests were given within minutes of placement, but facilitation was obtained for as long as 4 hr. Improved performance was obtained as soon as rats acquired the procedural aspects of the task but did not increase with subsequent practice. Improved performance was also obtained when pre-trained rats were tested in a novel environment. Despite the advantage conferred by exposure to the target platform, test swims were not accurate, placement-induced improvement was not as great as that following a single swimming trial, and placement combined with a swim resulted in best performance. The results suggest that rats use associative learning processes rather than cognitive mapping to solve place problems in a swimming pool.

Animals↗
PubMed2006

Phase transitions in coupled map lattices and in associated probabilistic cellular automata.

Analytical tools are applied to investigate piecewise linear coupled map lattices in terms of probabilistic cellular automata. The so-called disorder condition of probabilistic cellular automata is closely related with attracting sets in coupled map lattices. The importance of this condition for the suppression of phase transitions is illustrated by spatially one-dimensional systems. Invariant densities and temporal correlations are calculated explicitly. Ising type phase transitions are found for one-dimensional coupled map lattices acting on repelling sets and for a spatially two-dimensional Miller-Huse-like system with stable long time dynamics. Critical exponents are calculated within a finite size scaling approach. The relevance of detailed balance of the resulting probabilistic cellular automaton for the critical behavior is pointed out.

Journal Article↗
PubMed1989

Phosphorylation of microtubule-associated protein 2 by MAP kinase primarily involves the projection domain.

Chymotryptic digestion was used to localize the sites in microtubule-associated protein 2 which are preferentially phosphorylated in vitro by MAP kinase, an insulin-stimulated serine/threonine kinase which efficiently utilizes high molecular weight MAPs as substrates. MAP kinase phosphorylates sites in the projection domain almost exclusively; less than 6% of the phosphate incorporated by MAP kinase was found in the tubulin binding domain. This site specificity is in marked contrast to that of the catalytic subunit of cAMP dependent protein kinase, and most other protein kinases phosphorylating MAP-2, which extensively phosphorylate the tubulin binding domain.

Animals↗
PubMed1993

Restriction map of a virulence-associated plasmid of Rhodococcus equi.

The restriction cleavage map of a virulence-associated plasmid pREAT701 of Rhodococcus equi was constructed with EcoRI and HindIII by means of cloning the restriction fragments, cross Southern hybridization with each fragment, and hybridization with probes generated by modified inverse PCR. The genetic region responsible for expression of virulence-associated 15- to 17-kilodalton antigens was determined.

Blotting, Southern↗
PubMed1980

Immunofluorescence localization of HeLa cell microtubule-associated proteins on microtubules in vitro and in vivo.

Rabbit antisera were prepared against the two major groups of microtubule-associated proteins (MAPs) from HeLa cells, proteins of approximately 210,000 molecular weight (210k MAPs), and 125,000 mol wt (125k MAPs). These antisera were characterized by a sensitive antigen detection technique that employs immunofluorescence to localize cross-reactive material in polyacrylamide gels. Antisera prepared against the 210k MAPs showed no cross-reactivity with extract proteins of other molecular weights or with bran MAPs, but did react with proteins of 210,000 mol wt and with a minor HeLa MAP of approximately 255,000 mol wt. Antibodies prepared against the 125k HeLa MAPs, likewise, reacted specifically with proteins of 125,000 mol wt, showing no cross-reactivity with other HeLa extract proteins or porcine brain MAPs. Immunofluorescence with the 210k and 125k MAP antisera was used to demonstrate the association of each of the MAPs with fixed HeLa microtubules in vitro. In addition, immunofluorescence with these antisera revealed a physical association of 210k and 125k MAPs with a Colcemid-sensitive fiber network in fixed interphase and mitotic HeLa cells. Thus, using specific, well-characterized antisera to the two major groups of HeLa MAPs, we have shown that these proteins are components of microtubules in HeLa cells.

Fluorescent Antibody Technique↗
PubMed1992

Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization.

Bovine brain microtubule protein, containing both tubulin and microtubule-associated proteins, undergoes ADP-ribosylation in the presence of [14C]NAD+ and a turkey erythrocyte mono-ADP-ribosyltransferase in vitro. The modification reaction could be demonstrated in crude brain tissue extracts where selective ADP-ribosylation of both the alpha and beta chains of tubulin and of the high molecular weight microtubule-associated protein MAP-2 occurred. In experiments with purified microtubule protein, tubulin dimer, the high molecular weight microtubule-associated protein MAP-2, and another high molecular weight mirotubule-associated protein which may be a MAP-1 species were heavily labeled. Tubulin and MAP-2 incorporated [14C]ADP-ribose to an average extent of approximately 2.4 and 30 mol of ADP-ribose/mol of protein, respectively. Assembly of microtubule protein into microtubules in vitro was inhibited by ADP-ribosylation, and incubation of assembled steady-state microtubules with ADP-ribosyltransferase and NAD+ resulted in rapid depolymerization of the microtubules. Thus, the eukaryotic enzyme can ADP-ribosylate tubulin and microtubule-associated proteins to much greater extents than previously observed with cholera and pertussis toxins, and the modification can significantly modulate microtubule assembly and disassembly.

ADP Ribose Transferases↗
PubMed2006

Linkage mapping of gene-associated SNPs to pig chromosome 11.

Single nucleotide polymorphisms (SNPs) were discovered in porcine expressed sequence tags (ESTs) orthologous to genes from human chromosome 13 (HSA13) and predicted to be located on pig chromosome 11 (SSC11). The SNPs were identified as sequence variants in clusters of EST sequences from pig cDNA libraries constructed in the Sino-Danish pig genome project. In total, 312 human gene sequences from HSA13 were used for similarity searches in our pig EST database. Pig ESTs showing significant similarity with HSA13 genes were clustered and candidate SNPs were identified. Allele frequencies for 26 SNPs were estimated in a group of 80 unrelated pigs from Danish commercial pig breeds: Duroc, Hampshire, Landrace and Large White. Eighteen of the 26 SNPs genotyped in the PiGMaP Reference Families were mapped by linkage analysis to SSC11. The EST-based SNPs published here are new genetic markers useful for linkage and association studies in commercial and experimental pig populations. This study represents the first gene-associated SNP linkage map of pig chromosome 11 and adds new comparative mapping information between SSC11 and HSA13. Furthermore, our data facilitate future studies aimed at the identification of interesting regions on pig chromosome 11, positional cloning and fine mapping of quantitative trait loci in pig.

Animals↗