Live sequence charts to model medical information

ABSTRACT: BACKGROUND: Medical records accumulate data concerning patient health and the natural history of disease progression. However, methods to mine information systematically in a form other than an electronic health record are not yet available. The purpose of this study was to develop an object modeling technique as a first step towards a formal database of medical records. METHOD: Live Sequence Charts (LSC) were used to formalize the narrative text obtained during a patient interview. LSCs utilize a visual scenario-based programming language to build object models. LSC extends the classical language of UML message sequence charts (MSC), predominantly through addition of modalities and providing executable semantics. Interobject scenarios were defined to specify natural history event interactions and different scenarios in the narrative text. Result A simulated medical record was specified into LSC formalism by translating the text into an object model that comprised a set of entities and events. The entities described the participating components (i.e., doctor, patient and record) and the events described the interactions between elements. A conceptual model is presented to illustrate the approach. An object model was generated from data extracted from an actual new patient interview, where the individual was eventually diagnosed as suffering from Chronic Fatigue Syndrome (CFS). This yielded a preliminary formal designated vocabulary for CFS development that provided a basis for future formalism of these records. CONCLUSIONS: Translation of medical records into object models created the basis for a formal database of the patient narrative that temporally depicts the events preceding disease, the diagnosis and treatment approach. The LSCs object model of the medical narrative provided an intuitive, visual representation of the natural history of the patient's disease.     

Salivary gland branching morphogenesis: a quantitative systems analysis of the Eda/Edar/NFκB paradigm

Background  

Ectodysplasin-A appears to be a critical component of branching morphogenesis. Mutations in mouse Eda or human EDA are associated with absent or hypoplastic sweat glands, sebaceous glands, lacrimal glands, salivary glands (SMGs), mammary glands and/or nipples, and mucous glands of the bronchial, esophageal and colonic mucosa. In this study, we utilized Eda ^Ta (Tabby) mutant mice to investigate how a marked reduction in functional Eda propagates with time through a defined genetic subcircuit and to test the proposition that canonical NFκB signaling is sufficient to account for the differential expression of developmentally regulated genes in the context of Eda polymorphism.     

Effect of AMF application on growth, productivity and susceptibility to Verticillium wilt of olives grown under desert conditions

The effect of arbuscular mycorrhizal fungi (AMF) on olive (Olea europaea) growth and development was followed for 4 years after transplanting in irrigated commercial orchards under arid conditions. Sites I and II were irrigated with saline water (EC?=?4.5 dS/m). In site I, the soil was infested with Verticillium dahliae and olive varieties ‘Picual’ (Verticillium susceptible) and ‘Barnea’ (relatively Verticillium tolerant) were tested. In site II, the soil was virgin soil (previously non-cultivated soil) and olive varieties ‘Souri’ and ‘Barnea’ were tested. Plants for all sites were inoculated in the nursery with Glomus intraradices alone or in a mixture with G. mosseae. Relative to non-inoculated trees, AMF colonization enhanced vegetative growth, expressed as tree height and trunk circumference, at all sites. At first commercial harvest, AMF-treated trees had higher fruit and oil yields than non-mycorrhitic controls. Under saline water irrigation, differences between inoculated and non-inoculated treatments were reduced in the slow-growing ‘Souri’ but remained apparent in the modern fast-growing ‘Barnea’. AMF colonization did not appear to improve tolerance of either ‘Picual’ or ‘Barnea’ to V. dahliae, and both were more susceptible than the non-inoculated controls. Thus inoculation of olive plants with AMF improves transplant growth and adaptation in arid areas during the first 3 years of growth and until the first commercial harvesting season.     

Citrus chlorophyllase dynamics at ethylene-induced fruit color-break: a study of chlorophyllase expression, posttranslational processing kinetics, and in situ intracellular localization

Fruit color-break is the visual manifestation of the developmentally regulated transition of chloroplasts to chromoplasts during fruit ripening and often involves biosynthesis of copious amounts of carotenoids concomitant with massive breakdown of chlorophyll. Regulation of chlorophyll breakdown at different physiological and developmental stages of the plant life cycle, particularly at fruit color-break, is still not well understood. Here, we present the dynamics of native chlorophyllase (Chlase) and chlorophyll breakdown in lemon (Citrus limon) fruit during ethylene-induced color-break. We show, using in situ immunofluorescence on ethylene-treated fruit peel (flavedo) tissue, that citrus Chlase is located in the plastid, in contrast to recent reports suggesting cytoplasmic localization of Arabidopsis (Arabidopsis thaliana) Chlases. At the intra-organellar level, Chlase signal was found to overlap mostly with chlorophyll fluorescence, suggesting association of most of the Chlase protein with the photosynthetic membranes. Confocal microscopy analysis showed that the kinetics of chlorophyll breakdown was not uniform in the flavedo cells. Chlorophyll quantity at the cellular level was negatively correlated with plastid Chlase accumulation; plastids with reduced chlorophyll content were found by in situ immunofluorescence to contain significant levels of Chlase, while plastids containing still-intact chlorophyll lacked any Chlase signal. Immunoblot and protein-mass spectrometry analyses were used to demonstrate that citrus Chlase initially accumulates as an approximately 35-kD precursor, which is subsequently N-terminally processed to approximately 33-kD mature forms by cleavage at either of three consecutive amino acid positions. Chlase plastid localization, expression kinetics, and the negative correlation with chlorophyll levels support the central role of the enzyme in chlorophyll breakdown during citrus fruit color-break.     

Studies of hematoporphyrin and hematoporphyrin derivative equilibria in heterogeneous systems. Porphyrin-liposome binding and porphyrin aqueous dimerization

Two processes of porphyrins in heterogeneous systems containing aqueous and membrane phases have been studied with hematoporphyrin and hematoporphyrin derivative: Dimerization equilibrium in the aqueous phases and porphyrin-membrane binding equilibrium using liposomes as models for biological membranes. The interrelationship of aqueous aggregations and membrane binding was probed and the porphyrin aggregation state in the membrane, at equilibrium, was assessed. Fluorimetric techniques were employed. The dimerization equilibrium constants, at neutral pH and 37°C were found to be 2.8 · 10⁵ M⁻¹ and 1.9 · 10⁶ M⁻¹ for hematoporphyrin and its derivative, respectively. Over a porphyrin concentration range going from monomer-dominant to dimer-dominant systems, we have found that only monomers are bound to the membrane. The respective monomer-liposome binding constants, found to be independent of the initial monomer/dimer distribution in the aqueous phase, were determined to be 1.6 · 10³ M⁻¹ and 4.1 · 10³ M⁻¹ at neutral pH and 37°C for hematoporphyrin and its derivative, respectively. The monomer-liposome interaction was found to perurb the initial monomer/dimer distribution in the aqueous phase, so that the monomers residing at equilibrium in the membrane originate from both monomers and dimers in the aqueous phase.     

Significant host- and environment-dependent differentiation among highly sporadic fungal endophyte communities in cereal crops-related wild grasses

Endophytic fungi compose a significant part of plant microbiomes. However, while a small number of fungal taxa have proven beneficial impact, the vast majority of fungal endophytes remain uncharacterized, and the drivers of fungal endophyte community (FEC) assembly are not well understood. Here, we analysed FECs in three cereal crops-related wild grasses – Avena sterilis, Hordeum spontaneum and Aegilops peregrina – that grow in mixed populations in natural habitats. Taxa in Ascomycota class Dothideomycetes, particularly the genera Alternaria and Cladosporium, were the most abundant and prevalent across all populations, but there was also high incidence of basidiomyceteous yeasts of the class Tremellomycetes. The fungal community was shaped to large extent by stochastic processes, as indicated by high level of variation even between individuals from local populations of the same plant species, and confirmed by the neutral community model and Raup-Crick index. Nevertheless, we still found strong determinism in FEC assembly with both incidence and abundance data sets. Substantial differences in community composition across host species and locations were revealed. Our research demonstrated that assembly of FECs is affected by stochastic as well as deterministic processes and suggests strong effects of environment heterogeneity and plant species on community composition. In addition, a small number of taxa had high incidence and abundance in all of the 15 populations. These taxa represent an important part of the core FEC and might be of general functional importance.     

Correction method for null alleles in species with variable microsatellite flanking regions, a case study of the black-lipped pearl oyster Pinctada margaritifera

In bivalves, heterozygote deficiencies and departures from Hardy-Weinberg equilibrium (HWE) in microsatellite analysis are common and mainly attributed to inbreeding, genetic patchiness (Walhund effect), or null alleles. We checked for the occurrence of null alleles at 3 microsatellite loci in 3 populations of black-lipped pearl oyster, Pinctada margaritifera, using a step-by-step method to re-amplify homozygotes and null individuals with redesigned primer pair combinations. After amplification with original primer pairs, the 3 populations exhibited null alleles, absence of structure, and significant departure from HWE for all 3 loci due to heterozygote deficiencies. After 3 re-amplification steps, with modified primer sets, all loci were corrected for null alleles. Once corrected, all populations appeared at HWE, demonstrating that null alleles were responsible for the initial disequilibrium of the populations. Furthermore, analysis from corrected genotypes demonstrates significant genetic differentiation for one population from the other 2.     

The role of COBRA‐LIKE 2 function,as part of the complex network of interacting pathways regulating Arabidopsis seed mucilage polysaccharide matrix organization

The production of hydrophilic mucilage along the course of seed coat epidermal cell differentiation is a common adaptation in angiosperms. Previous studies have identified COBRA‐LIKE 2 (COBL2), a member of the COBRA‐LIKE gene family, as a novel component required for crystalline cellulose deposition in seed coat epidermal cells. In recent years, Arabidopsis seed coat epidermal cells (SCEs), also called mucilage secretory cells, have emerged as a powerful model system for the study of plant cell wall components biosynthesis, secretion, assembly and de muro modification. Despite accumulating data, the molecular mechanism of COBL function remains largely unknown. In the current research, we utilized genetic interactions to study the role of COBL2 as part of the protein network required for seed mucilage production. Using correlative phenotyping of structural and biochemical characteristics, unique features of the cobl2 extruded mucilage are revealed, including: ‘unraveled’ ray morphology, loss of primary cell wall ‘pyramidal’ organization, reduced Ruthenium red staining intensity of the adherent mucilage layer, and increased levels of the monosaccharides arabinose and galactose. Examination of the cobl2cesa5 double mutant provides insight into the interface between COBL function and cellulose deposition. Additionally, genetic interactions between cobl2 and fei1fei2 as well as between each of these mutants to mucilage‐modified 2 (mum2) suggest that COBL2 functions independently of the FEI‐SOS pathway. Altogether, the presented data place COBL2 within the complex protein network required for cell wall deposition in the context of seed mucilage and introduce new methodology expending the seed mucilage phenotyping toolbox.