A computer program for testing average partial association in three-way contingency tables (PARCAT).

PARCAT is a computer program which implements alternative tests for average partial association in three-way contingency tables within the framework of the product multiple hypergeometric probability model. Primary attention is directed at the relationship between two of the variables, controlling for the effects of a covariable. This approach is essentially a multivariate extension of the Cochran/Mantel-Haenszel test to sets of (s x r) tables. A set of scores such as uniform, ridits, or probits can be assigned to categories which are ordinally scaled. In particular, if ridit scores with midranks assigned for ties are utilized, this procedure is equivalent to a partial Kruskal-Wallis test when one variable is ordinally scaled, and is equivalent to a partial Spearman rank correlation test when both variables are ordinally scaled.     

Effects of tropomyosin internal deletions on thin filament function.

Striated muscle tropomyosin spans seven actin monomers and contains seven quasi-repeating regions with loose sequence similarity. Each region contains a hypothesized actin binding motif. To examine the functions of these regions, full-length tropomyosin was compared with tropomyosin internal deletion mutants spanning either five or four actins. Actin-troponin-tropomyosin filaments lacking tropomyosin regions 2-3 exhibited calcium-sensitive regulation in in vitro motility and myosin S1 ATP hydrolysis experiments, similar to filaments with full-length tropomyosin. In contrast, filaments lacking tropomyosin regions 3-4 were inhibitory to these myosin functions. Deletion of regions 2-4, 3-5, or 4-6 had little effect on tropomyosin binding to actin in the presence of troponin or troponin-Ca(2+), or in the absence of troponin. However, all of these mutants inhibited myosin cycling. Deletion of the quasi-repeating regions diminished the prominent effect of myosin S1 on tropomyosin-actin binding. Interruption of this cooperative, myosin-tropomyosin interaction was least severe for the mutant lacking regions 2-3 and therefore correlated with inhibition of myosin cycling. Regions 3, 4, and 5 each contributed about 1.5 kcal/mol to this process, whereas regions 2 and 6 contributed much less. We suggest that a myosin-induced conformational change in actin facilitates the azimuthal repositioning of tropomyosin which is an essential part of regulation.     

Intramolecular backfolding of the carboxyl-terminal end of MxA protein is a prerequisite for its oligomerization.

Mx proteins are large GTPases, which play a pivotal role in the interferon type I-mediated response against viral infections. The human MxA inhibits the replication of several RNA viruses and is organized in oligomeric structures. Using two different experimental approaches, the mammalian two-hybrid system and an interaction dependent nuclear translocation approach, three domains in the carboxyl-terminal moiety were identified that are involved in the oligomerization of MxA. The first consists of a carboxyl-terminal amphipathic helix (LZ1), which binds to a more proximal part of the same molecule. This intramolecular backfolding is a prerequisite for the formation of an intermolecular complex. This intermolecular interaction is mediated by two domains, a poorly defined region generated by the intramolecular interaction and a domain located between amino acids 363 and 415. Co-expression of wild-type MxA with various mutant fragments thereof revealed that the presence of the carboxyl-terminal region comprising the amphipathic helices LZ1 and LZ2 is necessary and sufficient to exert a dominant negative effect. This finding suggests that the functional interference of the carboxyl-terminal region is due to competition for binding of an as yet unidentified cellular or viral target molecules.     

Experimental use of fibrin glue to induce site-directed osteogenesis from cultured periosteal cells

The purpose of this study was to determine whether a combination of fibrin glue and cultured periosteal cells will result in new bone formation at heterotopic sites in nude mice. Growing cells and developing matrices surrounding periosteal explants from the diaphyses of radii of newborn calves were minced and mixed with fibrin glue in a syringe. The cell/matrix-fibrin glue admixture was then injected into the subcutaneous space on the dorsum of athymic nude mice. After 12 weeks of implantation, gross morphology and histologic investigations showed newly formed bone structures in all cell/matrix-fibrin glue admixtures, but none in fibrin glue injected alone and used as control samples. Osteopontin, a protein important in bone development, was identified by a Western blot assay of the cell/matrix-fibrin glue composite. This study supports the feasibility of initiating site-directed formation of bone structures at heterotopic tissue sites by means of injection of cultured periosteal cells and matrix in a fibrin glue carrier.     

Quality determination and the repair of poor quality spots in array experiments

Background  

A common feature of microarray experiments is the occurence of missing gene expression data. These missing values occur for a variety of reasons, in particular, because of the filtering of poor quality spots and the removal of undefined values when a logarithmic transformation is applied to negative background-corrected intensities. The efficiency and power of an analysis performed can be substantially reduced by having an incomplete matrix of gene intensities. Additionally, most statistical methods require a complete intensity matrix. Furthermore, biases may be introduced into analyses through missing information on some genes. Thus methods for appropriately replacing (imputing) missing data and/or weighting poor quality spots are required.     

A Taxonomic Search Engine: Federating taxonomic databases using web services

Background  

The taxonomic name of an organism is a key link between different databases that store information on that organism. However, in the absence of a single, comprehensive database of organism names, individual databases lack an easy means of checking the correctness of a name. Furthermore, the same organism may have more than one name, and the same name may apply to more than one organism.     

Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis

Introduction  

The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA).     

Developmental changes in the neurotransmitter properties of dissociated sympathetic neurons: a cytochemical study of the effects of medium

Sympathetic principal neurons were dissociated from the superior cervical ganglia of newborn rats and grown in several culture conditions shown previously to affect the transmitter status of the neurons. In three of these conditions the neurons are known to develop adrenergic functions over a 3- to 4-week period; in a fourth condition, they develop predominantly cholinergic functions. In this ultrastructural study, the transmitter status of the neurons during development in the several different media was examined after permanganate fixation which causes a granular precipitate in synaptic vesicles containing norepinephrine (small granular vesicles or SGV). It was found that as early as 4 days after plating, synapses and varicosities were present. In all four conditions, all of the terminals contained numerous SGV, indicating that the neurons both synthesize and store norepinephrine. Under “adrenergic” growth conditions, the terminals remained adrenergic in appearance during further development. Under “cholinergic” conditions, terminals of cholinergic appearance were present as early as 7 days and their incidence increased with time. Although the cholinergic terminals contained little or no endogenous norepinephrine, many were initially able to take up and store exogenous catecholamine. These results indicate that the dissociated sympathetic neurons of newborn rats which survive in culture acquired adrenergic transmitter functions early. Under “cholinergic” culture conditions, the neurons lose the ability to synthesize detectable quantities of norepinephrine; the ability to take up and store detectable quantities of exogenous catecholamines disappears more slowly.     

Solubilization of gellan gels by chelation of cations

Summary Chelation solubilization of gellan under mild conditions has been accomplished for the first time by exposure to either 10 mM sodium citrate buffer (pH 6.0) or to 1 mM sodium hexametaphosphate (pH 6.6). The citrate system was preferred for most applications since its is a ubiquitous cellular component, its solutions are autoclavable, and because viable plant tissues, fungi, and bacteria could be recovered from culture. Such recovery is not possible from more commonly used media such as agar.