Biomedical subjects

M A Walker

Publications and source records attributed to M A Walker.

At least 19 recordsLinked to original sources

PubMed2006

Refined mapping of the Pierce's disease resistance locus, PdR1, and Sex on an extended genetic map of Vitis rupestris x V. arizonica.

A framework genetic map based on genomic DNA-derived SSR, EST-derived SSR, EST-STS and EST-RFLP markers was developed using 181 genotypes generated from D8909-15 (female) x F8909-17 (male), the '9621' population. Both parents are half siblings with a common female parent, Vitis rupestris 'A. de Serres', and different male parents (forms of V. arizonica). A total of 542 markers were tested, and 237 of them were polymorphic for the female and male parents. The female map was developed with 159 mapped markers covering 865.0 cM with an average marker distance of 5.4 cM in 18 linkage groups. The male map was constructed with 158 mapped molecular markers covering 1055.0 cM with an average distance of 6.7 cM in 19 linkage groups. The consensus '9621' map covered 1154.0 cM with 210 mapped molecular markers in 19 linkage groups, with average distance of 5.5 cM. Ninety-four of the 210 markers on the consensus map were new. The 'Sex' expression locus segregated as single major gene was mapped to linkage group 2 on the consensus and the male map. PdR1, a major gene for resistance to Pierce's disease, caused by the bacterium Xylella fastidiosa, was mapped to the linkage group 14 between markers VMCNg3h8 and VVIN64, located 4.3 and 2.7 cM away from PdR1, respectively. Differences in segregation distortion of markers were also compared between parents, and three clusters of skewed markers were observed on linkage groups 6, 7 and 14.

Chromosome Mapping↗

PubMed2006

Genetic linkage map of the interspecific grape rootstock cross Ramsey (Vitis champinii) x Riparia Gloire (Vitis riparia).

The first genetic linkage map of grape derived from rootstock parents was constructed using 188 progeny from a cross of Ramsey (Vitis champinii) x Riparia Gloire (V. riparia). Of 354 simple sequence repeat markers tested, 205 were polymorphic for at least one parent, and 57.6% were fully informative. Maps of Ramsey, Riparia Gloire, and the F1 population were created using JoinMap software, following a pseudotestcross strategy. The set of 205 SSRs allowed for the identification of all 19 Vitis linkage groups (2n=38), with a total combined map length of 1,304.7 cM, averaging 6.8 cM between markers. The maternal map consists of 172 markers aligned into 19 linkage groups (1,244.9 cM) while 126 markers on the paternal map cover 18 linkage groups (1,095.5 cM). The expected genome coverage is over 92%. Segregation distortion occurred in the Ramsey, Riparia Gloire, and consensus maps for 10, 13, and 16% of the markers, respectively. These distorted markers clustered primarily on the linkage groups 3, 5, 14 and 17. No genome-wide difference in recombination rate was observed between Ramsey and Riparia Gloire based on 315 common marker intervals. Fifty-four new Vitis-EST-derived SSR markers were mapped, and were distributed evenly across the genome on 16 of the 19 linkage groups. These dense linkage maps of two phenotypically diverse North American Vitis species are valuable tools for studying the genetics of many rootstock traits including nematode resistance, lime and salt tolerance, and ability to induce vigor.

Chromosome Mapping↗

PubMed2006

Identification and molecular mapping of PdR1, a primary resistance gene to Pierce's disease in Vitis.

A major quantitative trait locus (QTL) controlling resistance to Pierce's disease (PD) of grape, caused by the bacterium Xylella fastidiosa (Xf), was identified on a Vitis linkage map and denoted as 'Pierce's disease resistance 1' (PdR1). Placement of the locus was accomplished by evaluating a family of full-sib progeny from a cross of two PD-resistant interspecific hybrids with resistance inherited from Vitis arizonica. Resistance was measured under greenhouse conditions by direct quantification of Xf numbers in stem tissues as well as by evaluation of disease symptoms based on leaf scorch and a cane maturation index (CMI). A large QTL (LOD 17.2) accounting for 72% of the phenotypic variance in bacterial numbers was localized to linkage group 14 of the male parent F8909-17. The approximate 95% confidence interval around the QTL peak extended 5.7 cM when using composite interval mapping. The other disease evaluation methods (leaf scorch and CMI, respectively) placed the resistance QTL to the same region on linkage group 14, although at wider 95% confidence intervals (6.0 and 7.5 cM), lower peak LOD scores (11.9 and 7.7) and accounting for less phenotypic variance (59 and 42%). This is the first report of an Xf resistance QTL mapped in any crop species. The relevance of the markers located in the region spanning the QTL will be discussed, addressing their usefulness for the development of PD-resistant grape cultivars.

Chromosome Mapping↗

PubMed2005

Inheritance of resistance to Xylella fastidiosa within a Vitis rupestris x Vitis arizonica hybrid population.

The inheritance of resistance to Xylella fastidiosa (Xf), the bacterium which causes Pierce's disease (PD) in grapevines, was evaluated within a factorial mating design consisting of 16 full-sib families with resistance derived from Vitis arizonica interspecific hybrids. Measurements of disease progression under greenhouse conditions were based on quantitative assessment of Xf populations in stem tissues and on three phenotypic scores: leaf scorch, a cane maturation index (CMI) and an index that incorporated shoot stunting into the cane maturation index (CMSSI). Measurement of bacterial populations yielded the highest broad-sense heritability for resistance on a genotype mean basis (0.97), indicating that this measure of resistance was the least effected by environmental variation. Narrow-sense heritability of PD resistance was moderately high and measured 0.52, 0.60, 0.63 and 0.37 for Xf populations, CMI scores, CMSSI scores and leaf scorch values, respectively. Complex segregation analysis using the computer program Statistical Analysis for Genetic Epidemiology (SAGE: ) strongly indicated the existence of a major gene for PD resistance, which accounted for 91% of the total genetic variance. Conversion of the quantitative data into qualitative resistance levels and evaluation via a chi-square analysis showed that 15 of the 16 families segregated in accordance with a single gene hypothesis with a dominant allele controlling PD resistance. These data indicate that the trait should be relatively easy to pass on from parents to progeny in a breeding program for the development of PD-resistant grape cultivars, particularly when selection is based on cane maturation scores or stem Xf populations.

Breeding↗

PubMed2005

The continued value of central histopathological review of testicular tumours.

AIMS: Central histopathological review of testicular tumours prior to definitive treatment can have an important impact on patient management. This study was designed to assess the continued value of central review in the light of increasing subspecialization and increased numbers of consultant histopathologists. MATERIALS AND RESULTS: The original and review reports of 291 testicular cancer specimens from 1998 to 2002 were analysed, looking particularly at major diagnosis, vascular invasion and the tumour elements within non-seminomatous germ cell tumours (NSGCT). When a diagnosis was altered any effect on subsequent patient management was assessed. There was a discrepancy in tumour type in 11 cases (4%) compared with 6% in 1992-1997. The commonest change was from seminoma to NSGCT or combined germ cell tumour (5/11). There was also diagnostic difficulty with spermatocytic seminoma (3/11). The clinical management of all 11 cases was influenced as a result of the review diagnosis. Discrepancies in vascular invasion were noted in 13 of the 126 NSGCTs (10%) compared with 20% in 1992-1997. Differences in NSGCT tumour elements, though clinically less important, were frequent in both groups. CONCLUSIONS: There continues to be a small number of significant and clinically important errors identified following central histopathological review of testicular tumours. This study highlights the value of central review and supports its continued practice in the management of testicular tumours.

Aged↗

PubMed2004

A genetic linkage map of grape, utilizing Vitis rupestris and Vitis arizonica.

A genetic linkage map of grape was constructed, utilizing 116 progeny derived from a cross of two Vitis rupestris x V. arizonica interspecific hybrids, using the pseudo-testcross strategy. A total of 475 DNA markers-410 amplified fragment length polymorphism, 24 inter-simple sequence repeat, 32 random amplified polymorphic DNA, and nine simple sequence repeat markers-were used to construct the parental maps. Markers segregating 1:1 were used to construct parental framework maps with confidence levels >90% with the Plant Genome Research Initiative mapping program. In the maternal (D8909-15) map, 105 framework markers and 55 accessory markers were ordered in 17 linkage groups (756 cM). The paternal (F8909-17) map had 111 framework markers and 33 accessory markers ordered in 19 linkage groups (1,082 cM). One hundred eighty-one markers segregating 3:1 were used to connect the two parental maps' parents. This moderately dense map will be useful for the initial mapping of genes and/or QTL for resistance to the dagger nematode, Xiphinema index, and Xylella fastidiosa, the bacterial causal agent of Pierce's disease.

Base Sequence↗

PubMed2003

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Animals↗

PubMed2003

A postmortem study of the mediodorsal nucleus of the thalamus in schizophrenia.

Four studies have reported that the mediodorsal nucleus of the thalamus (MD) is smaller and contains fewer neurons in schizophrenia. The MD is a key node in a circuit proposed to be dysfunctional in the disorder. However, one study did not find a MD volume loss in schizophrenia, and all the studies to date are relatively small. Given the importance of establishing unequivocally the presence of MD pathology, we have carried out a study of the volume and number of neurons in the left and right MD in 21 patients with schizophrenia and 27 healthy comparison subjects. We also measured the size of MD neurons, and estimated total thalamic volume. We found no difference in the volume of the MD, the number of MD neurons, or the size of MD neurons in either hemisphere in schizophrenia. Neither was total thalamic volume altered. There are no obvious methodological or clinical factors to explain our failure to replicate the finding of MD involvement in schizophrenia. Hence our negative observations, in the largest sample yet investigated, cast doubt on the robustness and/or the generalisability of MD neuropathology in schizophrenia.

Adult↗

PubMed2003

Size of hippocampal pyramidal neurons in schizophrenia.

BACKGROUND: Meta-analyses of hippocampal size have indicated that this structure is smaller in schizophrenia. This could reflect a reduction in the size of constituent neurons or a reduced number of neurons. AIMS: To measure the size of hippocampal pyramidal neurons in the brains of people with and without schizophrenia. METHOD: Pyramidal neuron size in hippocampal subfields was estimated stereologically from sections taken at 5 mm intervals throughout the whole length of right and left hippocampi from the brains of 13 people with schizophrenia and 16 controls. Results were assessed using repeated-measures analysis of covariance looking for a main effect of diagnosis and gender, and interactions of these with side. RESULTS: We were unable to detect significant differences related to diagnosis, gender or side for any hippocampal subfield for this series of cases. CONCLUSIONS: For this series of brains, hippocampal cell size is unchanged in schizophrenia.

Analysis of Variance↗

PubMed2002

The unilateral swollen lower limb: etiology, investigation, and management.

The swollen lower limb, a common finding in routine clinical practice, is clinically challenging. The cause underlying this problem is often multifactorial, and its management may involve different specialties. It is important, though difficult, to avoid unnecessary and expensive investigations. The aim of this article is to provide an overview of the management of this problem by addressing the common causes, methods of assessment, diagnosis, and therapeutic options.

Journal Article↗

PubMed2001

Synthesis of a novel C-10 spiro-epoxide of paclitaxel.

New analogues of paclitaxel (1a, active constituent of Taxol) were synthesized containing an epoxide at the C-10 position. The introduction of the epoxide was carried out by selective removal of the C10-acetate followed by protection of the C2'- and C7-hydroxyl groups. After oxidation to yield a ketone at the C10-position, this intermediate was reacted with dimethylsulfonium ylide. Deprotection and further manipulations provide the C10-spiro epoxide of paclitaxel (1b) and the corresponding C7-MOM ether (1c).

Antineoplastic Agents, Phytogenic↗

PubMed2001

Simple sequence repeat analysis of a clonally propagated species: a tool for managing a grape germplasm collection.

The USDA germplasm repositories help to preserve the genetic variability of important crop species by collecting and maintaining representative cultivars and related germplasm. Simple sequence repeat markers with high allelic diversity were used to type 41 grapevines from 40 accessions. All vines were either seedless table grape cultivars or cultivars with names similar to table grape cultivars. The proportion of shared alleles was selected as the most appropriate statistical measure of genetic distance for this population. In conjunction with morphological traits, known synonyms were confirmed and a previously unknown synonym was discovered. An alleged synonym in the literature was disproved by the DNA data. The data were consistent with known parentage, where such data were available. Two mislabeled vines in the USDA collection were identified. UPGMA grouped the cultivars loosely into three groups: a group of nine mostly Middle Eastern cultivars, a group of 22 accessions mostly from Russia and Afghanistan that were morphologically similar to 'Thompson Seedless', and a third very loose group of 11 accessions consisting mostly of eastern European wine grape cultivars. The limitations and usefulness of this type of analysis are discussed.

Alleles↗

PubMed2001

Biology and management of grape phylloxera.

Grape phylloxera, Daktulosphaira vitifoliae (Homoptera: Phylloxeridae), is a worldwide pest of grapevines. Its life cycle has sexual and asexual portions with forms that feed from leaf and root galls. Not all forms occur throughout the insect's range. Root forms predominate on Vitis vinifera cultivars; leaf forms predominate on other Vitis species characteristic of the American native range. Other conditions influence expression of the life cycle. Hosts and conditions similarly affect life table performance. Damage to grapevines is by secondary soilborne pathogens attacking the feeding site and by physiological interaction of the insect with the grapevine, though the latter has not been well studied. Resistant rootstocks derived from native American Vitis are the primary control tool. The insect varies genetically and relative to performance on hosts. Use of insecticides is limited in effect, and other control methods are not proven. More research on the biology, ecology, and management of phylloxera is needed.

Animals↗

PubMed2001

Schizophrenia and the frontal lobes: post-mortem stereological study of tissue volume.

BACKGROUND: It has been suggested that there is frontal lobe involvement in schizophrenia, and that it may be lateralised and gender-specific. AIMS: To clarify the structure of the frontal lobes in schizophrenia in a post-mortem series. METHOD: The volume of white matter and cortical components of the frontal lobes was measured in brains of controls and patients with schizophrenia using planimetry and the Cavalieri principle. The components measured were: superior frontal gyrus, middle frontal gyrus, a composite of inferior frontal gyrus and orbito-frontal cortex, as well as total frontal lobe cortex and white matter. In addition, the anterior cingulate gyrus was measured. RESULTS: No diagnosis, gender, diagnosis x side, diagnosis x gender or diagnosis x gender x side interactions were observed in the volume of any of the components, the grey matter as a whole or the white matter. No evidence for volumetric inter-group differences was found for the anterior cingulate gyrus. CONCLUSIONS: Such structural abnormalities as are present in the frontal lobes are more subtle than straightforward alterations in tissue volume; they may include changes in shape and the pattern of gyral folding.

Adult↗

PubMed2001

Seasonal capacity of attached and detached vineyard roots to support grape phylloxera (Homoptera: Phylloxeridae).

Field experiments were conducted to evaluate population densities and survival, developmental rate, and fecundity of grape phylloxera, Daktulosphaira vitifoliae (Fitch), as influenced by root attachment or detachment from mature, field-grown, Vitis vinifera L. grapevines through the growing season. Experiments were performed using artificial infestations of California biotype A grape phylloxera. Thirty-day bioassays on attached- and detached-roots were repeated monthly from May to September in 1997 (cultivar 'Carignane') and April to September in 1998 (cultivar 'Thompson Seedless'). The bioassays showed that attached roots had lower population densities than detached roots in all months of both years. Densities varied by month, tending to be higher in spring than in summer. Of the population parameters studied, survival was most influenced by attachment condition, being higher on detached than on attached roots by up to 25-fold. These results imply the importance of vine-related mortality factors to grape phylloxera population density. Influence of root attachment condition on developmental rate and fecundity was not uniform across bioassay months for either year; however, in the four out of 21 assays where there was a significant difference it favored detached roots by twofold. Fruit harvest resulted in higher survival in the July assay but not for assays in August and September; however, neither developmental rate nor fecundity was affected by harvest in any ofthe assays. We conclude that mortality rather than nutritional factors are most limiting for field populations on susceptible vines. This work suggests that detachment of roots as occurs with root girdling by root pathogens may increase grape phylloxera populations on infested, susceptible vines. These results imply that excised root bioassays over-estimate grape phylloxera virulence and underestimate rootstock resistance.

Animals↗

PubMed2001

Ecological and genetic aspects of grape phylloxera Daktulosphaira vitifoliae (Hemiptera: Phylloxeridae) performance on rootstock hosts.

Performance and genetic variability of clonal lineages derived from one Californian and one German population of grape phylloxera, Daktulosphaira vitifoliae Fitch were studied on their natal grape rootstock host and on three novel hosts over four generations in an aseptic dual culture system. The ability of D. vitifoliae to adapt to new hosts was measured by changes in fitness (rm) over four generations. The performance of a given clonal lineage changed over successive generations, depending upon the host plant and the phylloxera group. Analysis of amplified fragment length polymorphism-polymerase chain reaction (AFLP-PCR) banding patterns from 40 individual parthenogenetic D. vitifoliae revealed equal levels of genetic variation both among the four clonal lineages analysed and within the different generations of one lineage. Analysis of molecular variance (AMOVA) showed no significant differences between the D. vitifoliae lineages reared on different host plants, nor was a correlation between host performance and genotype found.

Adaptation, Physiological↗

PubMed2000

A two-component pericyclic reaction for synthesis of substituted benzofurans and aryl-quaternary carbon bonds.

The reaction shown is presumed to be a new [3,3]-sigmatropic rearrangement involving an O-arylsulfoxonium species or related sulfurane. It allows a sulfoxide and a phenol to be joined and rearranged in one operation at or below room temperature, coupling an aromatic to a quaternary carbon and creating benzofurans or articulated dihydrobenzofurans in a number of examples.

Journal Article↗

PubMed2000

A null mutation in HLA-G is not associated with preeclampsia or intrauterine growth retardation.

Modulation of the expression of genes of the major histocompatibility complex (MHC) in tissues at the maternal-fetal interface almost certainly plays a role in successful development of the semi-allogeneic fetus. While expression of the classical class I genes (HLA-A, B, C) is low to non-existent at this site, the non-classical molecule, HLA-G, is expressed uniquely in fetal cells at the maternal-fetal interface. The recent demonstration that homozygotes for a deletion mutation in exon 3 (1597DeltaC) of HLA-G do not express the full-length HLA-G1 isoforms indicates a potential reduction in expression of this isoform in heterozygotes. If the full-length isoform of HLA-G (i.e. HLA-G1) contributes to proper invasion of maternal spiral arteries by extravillous cytotrophoblast, then 1597DeltaC heterozygotes could be at increased risk for disorders of trophoblast invasion. Two populations, infants with intrauterine growth retardation (IUGR) and infants of preeclamptic (PE) mothers, were genotyped for the 1597DeltaC polymorphism. The frequency of 1597DeltaC in these samples was not significantly different from healthy controls, suggesting that heterozygotes for this deletion mutation are not at significantly increased risk for PE or IUGR (P = 0.727 and 0.803, respectively).

Adolescent↗