A region of maize chromosome 2 affects response to downy mildew pathogens

Quantitative trait loci (QTLs) for downy mildew resistance in maize were identified based on co-segregation with linked restriction fragment length polymorphisms or simple sequence repeats in 220 F2 progeny from a cross between susceptible and resistant parents. Disease response was assessed on F3 families in nurseries in Egypt, Thailand, and South Texas and after inoculation in a controlled greenhouse test. Heritability of the disease reaction was high (around 93% in Thailand). One hundred and thirty polymorphic markers were assigned to the ten chromosomes of maize with LOD scores exceeding 4.9 and covering about 1,265 cM with an average interval length between markers of 9.5 cM. About 90% of the genome is located within 10 cM of the nearest marker. Three putative QTLs were detected in association with resistance to downy mildew in different environments using composite interval mapping. Despite environmental and symptom differences, one locus on chromosome 2 had a major effect and explained up to 70% of the phenotypic variation in Thailand where disease pressure was the highest. The other two QTLs on chromosome 3 and chromosome 9 had minor effects; each explained no more than 4% of the phenotypic variation. The three QTLs appeared to have additive effects on resistance, identifying one major gene and two minor genes that contribute to downy mildew resistance.     

Normative nerve conductions in the tail of rhesus macaques (Macaca mulatta)

BACKGROUND: The aim of this study was to test the feasibility of using the tail of Macaca mulatta for neurophysiological testing of the peripheral nervous system. METHODS: Motor and sensory nerve conduction studies (NCS) of the tail were obtained by surface stimulation and recording. The technique utilized was novel. Unlike other NCS obtained from other peripheral nerves, this technique did not require any special neurophysiological expertise. RESULTS: The latency of the motor and sensory response was 2.5 +/- 0.71 and 1.1 +/- 0.27 ms respectively. The amplitude of the motor and sensory response was 8.1 +/- 5.1 mV and 14.6 +/- 9.4 microV respectively. Similar to human beings, there was a statistically significant relationship between age and motor amplitude, motor latency and sensory latency. CONCLUSIONS: Based on our results, a relatively simple, reproducible neurophysiological monitoring technique of the peripheral nervous system is possible.     

FE65 interaction with the ApoE receptor ApoEr2

The adaptor protein FE65 interacts with the beta-amyloid precursor protein (APP) via its C-terminal phosphotyrosine binding (PTB) domain and affects APP processing and Abeta production. Our previous data demonstrate that the apoE receptor ApoEr2 co-precipitated with APP and suggest that there are extracellular and intracellular interactions between these two transmembrane proteins. We hypothesized that FE65 acts as an intracellular link between ApoEr2 and APP. Co-immunoprecipitation experiments in COS7 cells demonstrated an interaction between ApoEr2 and FE65 that depended on the N-terminal PTB domain of FE65. Full-length FE65 increased co-immunoprecipitation of ApoEr2 and APP. Full-length FE65 also increased surface expression of ApoEr2, as determined by surface protein biotinylation and live cell surface staining. Constructs containing both the C- and N-terminal PTB domains of FE65 increased secreted APP, secreted ApoEr2, APP C-terminal fragment, and ApoEr2 C-terminal fragment, but constructs containing only single PTB domains did not affect APP or ApoEr2 processing. In addition, full-length FE65 decreased Abeta to a significantly greater extent than individual FE65 domains. These data suggest that FE65 can bind APP and ApoEr2 at the same time and affect the processing of each.     

Dissection of a metastatic gene expression signature into distinct components

Background

Metastasis, the process whereby cancer cells spread, is in part caused by an incompletely understood interplay between cancer cells and the surrounding stroma. Gene expression studies typically analyze samples containing tumor cells and stroma. Samples with less than 50% tumor cells are generally excluded, thereby reducing the number of patients that can benefit from clinically relevant signatures.

Results

For a head-neck squamous cell carcinoma (HNSCC) primary tumor expression signature that predicts the presence of lymph node metastasis, we first show that reduced proportions of tumor cells results in decreased predictive accuracy. To determine the influence of stroma on the predictive signature and to investigate the interaction between tumor cells and the surrounding microenvironment, we used laser capture microdissection to divide the metastatic signature into six distinct components based on tumor versus stroma expression and on association with the metastatic phenotype. A strikingly skewed distribution of metastasis associated genes is revealed.

Conclusion

Dissection of predictive signatures into different components has implications for design of expression signatures and for our understanding of the metastatic process. Compared to primary tumors that have not formed metastases, primary HNSCC tumors that have metastasized are characterized by predominant down-regulation of tumor cell specific genes and exclusive up-regulation of stromal cell specific genes. The skewed distribution agrees with poor signature performance on samples that contain less than 50% tumor cells. Methods for reducing tumor composition bias that lead to greater predictive accuracy and an increase in the types of samples that can be included are presented.     

Dichotomous organization of the external globus pallidus

Different striatal projection neurons are the origin of?a?dual organization essential for basal ganglia function. We have defined an analogous division of labor in the external globus pallidus (GPe) of Parkinsonian rats, showing that the distinct temporal activities of two populations of GPe neuron in?vivo are?underpinned by distinct molecular profiles and axonal connectivities. A first population of prototypic GABAergic GPe neurons fire antiphase to subthalamic nucleus (STN) neurons, often express parvalbumin, and target downstream basal ganglia nuclei, including STN. In contrast, a second population (arkypallidal neurons) fire in-phase with STN neurons, express preproenkephalin, and only innervate the striatum. This novel cell type provides the largest extrinsic GABAergic innervation of striatum, targeting both projection neurons and interneurons. We conclude that GPe exhibits several core components of?a dichotomous organization as fundamental as?that in striatum. Thus, two populations of GPe neuron?together orchestrate activities across all basal ganglia nuclei in a cell-type-specific manner.     

Use of an A-T-rich DNA clone for identification and detection of Peronosclerospora sorghi

A recombinant plasmid, pMLY12-1, screened from a Peronosclerospora sorghi library hybridizes only to DNA of P. sorghi, or to DNA from leaves infected with P. sorghi, not to DNA of P. sorghi Thailand isolate, P. philippinensis, P. sacchari, or P. maydis. The terminal sequences of the 1.3-kb insert, which appears to contain mitochondrial DNA, are 85% A and T. No polymorphisms were detected when the probe was hybridized to Southern blots containing DNA from P. sorghi pathotype 1, pathotype 3, or a Botswana isolate digested with any of the eight restriction endonucleases tested. The banding patterns were the same whether DNA was extracted directly from the fungus or from infected leaves.     

Histidine Uptake in Strains of Neurospora crassa with Normal and Mutant Transport Systems

Kinetic parameters for three systems of active histidine uptake by germinated conidia of Neurospora crassa have been measured. Each system appears to follow typical Michaelis-Menten kinetics when studied separately from the other systems. Under the conditions studied, the general amino acid transport system was found to account for the major portion of histidine uptake from low concentrations. Three types of transport mutants with altered growth inhibition patterns were selected in a histidine auxotroph. Growth of one mutant, type bas(a), could be inhibited by the addition of methionine to a histidine-supplemented medium, and another type, neu(a), could be inhibited by the addition of arginine. These mutants were shown to be lacking active histidine uptake by the basic amino acid and neutral amino acid transport systems, respectively. Another type of double mutant (his-3, neu(r)) could be inhibited only by the addition of very high concentrations of methionine in the presence of arginine and histidine, and the mutation appeared to have altered the specificity of the neutral amino acid permease.