Applying FAIR Principles to Plant Phenotypic Data Management in GnpIS.

GnpIS is a data repository for plant phenomics that stores whole field and greenhouse experimental data including environment measures. It allows long-term access to datasets following the FAIR principles: Findable, Accessible, Interoperable, and Reusable, by using a flexible and original approach. It is based on a generic and ontology driven data model and an innovative software architecture that uncouples data integration, storage, and querying. It takes advantage of international standards including the Crop Ontology, MIAPPE, and the Breeding API. GnpIS allows handling data for a wide range of species and experiment types, including multiannual perennial plants experimental network or annual plant trials with either raw data, i.e., direct measures, or computed traits. It also ensures the integration and the interoperability among phenotyping datasets and with genotyping data. This is achieved through a careful curation and annotation of the key resources conducted in close collaboration with the communities providing data. Our repository follows the Open Science data publication principles by ensuring citability of each dataset. Finally, GnpIS compliance with international standards enables its interoperability with other data repositories hence allowing data links between phenotype and other data types. GnpIS can therefore contribute to emerging international federations of information systems.

Mining Plant Genomic and Genetic Data Using the GnpIS Information System.

GnpIS is an information system designed to help scientists working on plants and fungi to decipher the molecular and genetic architecture of trait variations by facilitating the navigation through genetic, genomic, and phenotypic information. The purpose of the present chapter is to illustrate how users can (1) explore datasets from phenotyping experiments in order to build new datasets for studying genotype × environment interactions in traits, (2) browse into the results of other genetic analysis data such as GWAS to generate or check working hypothesis about candidate genes or to identify important alleles and germplasms for breeding programs, and (3) explore the polymorphism in specific area of the genome using InterMine, JBrowse tools embedded in the GnpIS information system.

Chondrocyte deformation induces mitochondrial distortion and heterogeneous intracellular strain fields.

Chondrocyte mechanotransduction is poorly understood but may involve cell deformation and associated distortion of intracellular structures and organelles. This study quantifies the intracellular displacement and strain fields associated with chondrocyte deformation and in particular the distortion of the mitochondria network, which may have a role in mechanotransduction. Isolated articular chondrocytes were compressed in agarose constructs and simultaneously visualised using confocal microscopy. An optimised digital image correlation technique was developed to calculate the local intracellular displacement and strain fields using confocal images of fluorescently labelled mitochondria. The mitochondria formed a dynamic fibrous network or reticulum, which co-localised with microtubules and vimentin intermediate filaments. Cell deformation induced distortion of the mitochondria, which collapsed in the axis of compression with a resulting loss of volume. Compression generated heterogeneous intracellular strain fields indicating mechanical heterogeneity within the cytoplasm. The study provides evidence supporting the potential involvement of mitochondrial deformation in chondrocyte mechanotransduction, possibly involving strain-mediated release of reactive oxygen species. Furthermore the heterogeneous strain fields, which appear to be influenced by intracellular structure and organisation, may generate significant heterogeneity in mechanotransduction behaviour for cells subjected to identical levels of deformation.

Immunisation of fish by bath immersion using ultrasound.

Ultrasonic irradiations (USI) as a means to open routes in the skin, thus facilitating the transdermal delivery of vaccines that will improve the effectiveness of vaccination by immersion, are reviewed in this paper. Based on our recent results in goldfish and carp it could be summarized that: (i) USI significantly improved the antigen uptake and enhanced antibody response; (ii) the requirements for high antigen concentrations, which are needed for simple bath immersion, could be considerably reduced in presonicated fish; (iii) after bath immersion, the antigen was slowly released from the skin to the blood in which its presence could still be detected 24 hours later. This retardation of the antigen in the skin was suggested to be due to a possible interaction with cells of the local immune system, in which it is processed and recognized. It is concluded that the recent advances in biotechnology of immunization with recombinant DNA and the use of DNA vaccines, together with the improvement of their administration using USI, provide interesting prospects for the further application of vaccines against viral and even parasitic diseases of fish.

Augmentation of cardiac output and carotid blood flow by chest and abdomen phased compression cardiopulmonary resuscitation.

Phased compression cardiopulmonary resuscitation, whereby the chest and abdomen are compressed sequentially, is a new approach to the classical cardiopulmonary resuscitation technique, which is based on the compression of the chest alone. Six dogs with cardiac arrest were treated by external chest and abdominal compression using a rigid plexiglas suit lined with flexible perithoracic and periabdominal bladders. Fast inflation and deflation of the two independent bladders, together with forced ventilation of the lung, generated phased pressure pulses. The physiological variables monitored throughout the experiment included central venous, left ventricular, and central arterial pressures, carotid blood flow, cardiac output, and acid base balance. The phased compression technique was performed with phased time lags of 0, 150, 300, 400, 600, 700, and 850 ms between the abdominal and thoracic pressure pulses. A random sequence of the different phased compression modes, each lasting for 3-10 minutes, was applied during the prolonged resuscitation procedure that lasted for up to 70 minutes. By starting the abdominal compression 300-400 ms before the thoracic compression the carotid flow index improved by 77% (from 13% with simultaneous compression to 23% with phased compression) and the cardiac output index increased by 65% (from 7.8% with simultaneous compression to 12.5%). The results provide insight into the chest pump concept and the role of intrathoracic and intra-abdominal pressures in generating improved blood circulation during cardiopulmonary resuscitation, and show the advantages of phased compression over chest compression alone and simultaneous chest and abdominal compression.

Intrathoracic and abdominal pressure variations as an efficient method for cardiopulmonary resuscitation: studies in dogs compared with computer model results.

Intrathoracic pressure variations are currently proposed as the main flow-generation mechanisms in standard and modified cardiopulmonary resuscitation (CPR) techniques. A method of changing pressure within the thorax and abdomen without any degree of heart compression was developed and tested in dogs. Intrathoracic and abdominal pressure waves were induced by cyclic inflation and deflation of the lungs and of perithoracic and periabdominal balloons. Various modes of CPR, depending on the rate of cycling, the use of a periabdominal balloon inflation, and a delay between the abdominal and thoracic pressure waves, were studied during ventricular fibrillation. During artificial systole (high intrathoracic pressure phase), the pressure which developed in the right ventricle (96.7 +/- 20.5 mmHg) was higher than the pressure in the aorta (89.3 +/- 20.5 mmHg, p less than 0.001). In artificial diastole (low intrathoracic pressure phase), the right ventricular pressure (11.7 +/- 2.6 mmHg) was lower than the aortic pressure (17.5 +/- 3.3 mmHg, p less than 0.001). The average flow in the carotid artery was 21.7 +/- 7.8 ml . min-1, which was 18 +/- 6% of the baseline carotid flow before CPR. Three different factors were found to improve the efficiency of CPR: periabdominal balloon inflation simultaneous with the intrathoracic pressure waves; increased frequency of the pressure waves from 60 to 100 cycles per minute; and inflation of the periabdominal balloon 50 to 100 ms before the thoracic balloon. Blood-gas and acid-base balance analysis during CPR revealed well-oxygenated arterial blood with a marked respiratory alkalosis and a slowly developing metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung tissue resistance and hysteretic moduli of lung parenchyma.

Lung tissue resistance (Rti) represents a large and labile component of total pulmonary resistance, but the mechanism is unknown. One hypothesis that has received some support in the literature is that on exposure to contractile agonists airway smooth muscle shortens and then, by the agency of elastic interdependence, induces distortion in surrounding parenchyma. Parenchymal distortion induced in the vicinity of a constricted airway is a pure shear deformation, but currently there are no data available for shear hysteresivity. Guided by a microstructural model, we have assigned stiffness and hysteresivity to microstructural elements and then computed how those properties are expressed at the macroscale in bulk hysteresivities for both shear and volumetric expansion. Hysteresivity for volumetric expansion is shown to be a stiffness-weighted average of hysteresivities of all microstructural components. But as the hysteresivity of microstructural elements increases, that for shear deformation increases to some degree but eventually attains a plateau. Blunted hysteretic response in shear seems to be an intrinsic property of pressure-supported structures, like the lung, that require an inflating pressure to ensure mechanical stability. The analysis indicates that that part of Rti attributable to parenchymal distortion can be at most a small fraction of that attributable to volumetric expansion. These results are purely theoretical in nature, and this suggests that caution is necessary in their interpretation. However, the mechanical basis of the results is sufficiently general to conclude that the hypothesis that parenchymal distortion secondary to bronchoconstriction can account for Rti and its changes seems to be implausible.

A physiological model for predicting carboxyhemoglobin formation from exposure to carbon monoxide in rats.

A time-dependent simulation model, based on the Coburn-Forster-Kane equation, was written in Advanced Continuous Simulation Language to predict carboxyhemoglobin (HbCO) formation and dissociation in F-344 rats during and after exposure to 500 parts/million CO for 1 h. Blood-gas analysis and CO-oximetry were performed on samples collected during exposure and off-gassing of CO. Volume displacement plethysmography was used to measure minute ventilation (VE) during exposure. CO diffusing capacity in the lung (DLCO) was also measured. Other model parameters measured in the animals included blood pH, total blood volume, and Hb concentration. Comparisons between model predictions using values for VE, DLCO, and the Haldane coefficient cited in the literature and predictions using measured VE, DLCO, and calculated Haldane coefficient for individual animals were made. General model predictions using values for model parameters derived from the literature agreed with published HbCO values by a factor of 0.987 but failed to simulate experimental data. On average, the general model overpredicted measured HbCO level by nearly 9%. A specific model using the means of measured variables predicted HbCO concentration within a factor of 0.993. When experimentally observed parameter fluctuations were included, the specific model predictions reflected experimental effects on HbCO formation.

Ultrasound-facilitated transport of silver chloride (AgCl) particles in fish skin.

Electron-dense nano-particles in aqueous suspension were administered by immersion into the epidermis of fish using ultrasound in the therapeutic range. Enhanced permeability of the tissues to the particles was achieved by acoustic cavitation, which induced a controlled level of necrosis in the outer cell layers, and by non-cavitational exposures, which widened intercellular spaces of non-necrosed tissue in deeper regions of the epidermis. Both particle concentration and penetration depth were quantified using transmission electron microscopy. While cavitation-induced perforation was necessary for particles to penetrate into the tissues, non-cavitational exposures during immersions increased the particle flux towards the skin surface, as well as the diffusion rate of the particles within the epidermis and their depth of penetration. The technique described above may potentially be applied for non-stressful, mass-administration of substances into aquatic animals, as well as the relatively new field of ultrasound-facilitated delivery in moist epithelial tissues in humans.

Toxicant distribution in the Thomas Domes.

Measurement of test article concentration distribution for light gases have been made in the Thomas Dome inhalation chambers at Wright-Patterson Air Force Base, using propane as a test agent. The method used to analyze for inhomogeneities in test article spatial distribution deliberately varies the dome operational parameters rather than requiring extreme operational stability. The variation in test article concentration is analyzed by regression to determine which operational parameters most influence the test agent distribution. Unaccounted concentration variability is assumed to be the inherent spatial variation of the test article in the dome. The propane studies indicated that the spatial variation within the dome was 6.4% of the mean and that room air temperature at the top of the dome, propane analyzer baseline stability, and dome pressure were (listed in order of decreasing importance) the variables influencing the test article distribution.

DNA adduct formation by alachlor metabolites.

The extent of DNA adduct formation by alachlor [ArN(CH2OCH3)C(O)CH2Cl wherein Ar is 2,6-diethylphenyl] and its metabolites is used as a guide to deduce the causal agent(s) in the carcinogenicity of this major herbicide. [14C-phenyl]Alachlor is compared to its two metabolic cleavage products, [14C-phenyl]2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) [ArNHC(O)CH2Cl] and [14C-phenyl]2,6-diethylaniline (DEA) (ArNH2), and to [14C-methoxy]alachlor in various in vitro and in vivo systems. Horseradish peroxidase and hydrogen peroxide activate DEA, but not CDEPA or alachlor, for formation of adducts with calf thymus DNA, which probably involves 2,6-diethylnitrosobenzene (ArNO) as an intermediate. Mouse liver microsomes and NADPH are both required to enhance the binding from each labeled preparation to calf thymus DNA; 4-fold higher labeling is observed from [14C-methoxy]- than from [14C-phenyl]alachlor. This 4-fold preferential DNA labeling from the 14C-methoxy compound is likewise found in the liver of mice treated intraperitoneally. Mouse liver protein and hemoglobin are also labeled, in vivo, with [14C-phenyl]alachlor, -CDEPA and -DEA, and, as with the DNA, the labeling of these proteins is 1.5- to 2-fold higher with [14C-methoxy]alachlor. Metabolic studies indicate that ArN(CH2OCH2OH)C(O)CH2Cl is an intermediate in forming CDEPA and presumably formaldehyde in the mouse liver microsomal mixed-function oxidase system and in yielding the O-glucuronide of ArN(CH2OH)C(O)CH2Cl in the urine of alachlor-treated mice. These findings point to the N-CH2OCH2OH metabolite or formaldehyde as a reactive intermediate in forming a DNA-adduct and as a candidate proximate carcinogen.

Acute neurobehavioral effects in rats from exposure to HFC 134a or CFC 12.

1,1,1,2-Tetrafluoroethane (HFC 134a), a chlorine-free hydrofluoroalkane, is internationally replacing billions of pounds of dichlorodifluoromethane (CFC 12) for coolant, refrigerant and aerosol propellant applications. The ALC50 for HFC 134a in rats is 567,000 ppm for 4 h; its potential for cardiac epinephrine sensitization in beagle dogs is acceptable (75,000 ppm); and its capacity to induce carcinogenicity or developmental disorders in animals is minimal. HFC 134a, with a serum half life estimated at 4-11 min, has been accepted for use as a propellant in metered-dose inhalant products, implying a low human toxicity risk from periodic brief exposures. There has been little published human or animal research evaluating possible neurobehavioral toxicity from longer HFC 134a exposures, as may be expected to occur in operational scenarios. In this study, male Wistar rats were exposed to various concentrations of HFC 134a or CFC 12 for up to 30 min while performing in either a rotarod/motorized running wheel apparatus or in an operant chamber The relative neurobehavioral toxicity of CFC 12 and its ozone-depleting substance replacement HFC 134a was assessed by comparing both gross motor system incapacitation and more subtle changes in ability to perform an operant discrimination task. It was shown that exposure to HFC 134a or CFC 12 concentrations from 40,000 to 470,000 ppm, for up to 30 min, induced neurobehavioral deficits in every subject, ranging from reduced operant efficiency to apparent anesthesia. For neurobehavioral endpoints examined in these experiments, HFC 134a inhalation was shown to induce deficits more rapidly, and at lower concentrations when compared to CFC 12 exposure.

Effect of exposure route on measurement of blood pressure by tail cuff in F-344 rats exposed to OTTO Fuel II.

Male Fischer-344 rats demonstrated a dose-response of blood pressure (BP) to increasing doses of propylene glycol dinitrate (PGDN), the major constituent of OTTO Fuel II (OFII) following administration by subcutaneous injection. Dermal application of the same doses to separate groups of rats resulted in variable responses of BP that were unrelated to dose. A nose-only exposure system was developed but no effect on BP was observed in rats exposed to a nearly saturated atmosphere of PGDN (approx. 750 mg/m3 at 25 degrees C). This study has indicated both the difficulties associated with the use of tail cuff measurement of BP and the need for either a more sensitive or more specific biomarker of effect for exposure to nitrate esters.

3-Substituted 2-halopropenals: mutagenicity, detoxification and formation from 3-substituted 2,3-dihalopropanal promutagens.

The mutagenicity of halopropenals for Salmonella typhimurium strain TA100 is as follows (revertants/nmole): 2-halopropenals [H2C = C(X)CHO], F = less than 0.6, Cl = 135, Br = 1140 and I = less than 2.4; 3-substituted-2-halopropenals [CH3CH = C(X)CHO], Cl = 68 and Br = 108; [C6H5CH = C(X)CHO], Cl = less than 1 and Br = 5; [ClCH = C(Cl)CHO], 91; [CH3(CH2)2CH = C(Br)CHO], less than 1; [(CH3)2C = C(Br)CHO], less than 0.5. Each of the active compounds is detoxified by the liver S9 fraction. Glutathione also detoxifies the 2-halopropenals and 2-halobutenals, more rapidly for the bromo than the chloro analogs. The mutagenic potency on metabolic activation of the herbicide diallate by microsomes or the S9 fraction is attributable to approximately 50% conversion to 2-chloropropenal when corrected for detoxification in these systems or with GSH. There is no correlation between mutagenicity and reactivity with the model thiol, 4-nitrobenzenethiol. The mutagenicity of 2,3-dichloro- and 2,3-dibromo-propanals and the corresponding dihalobutanals is accounted for by their rapid dehydrohalogenation to the corresponding 2-haloalkenals under physiological conditions. Chemicals that are metabolized to 2,3-dichloropropanal, 2,3-dichlorobutanal, their dibromo analogs, or to the corresponding 2-halopropenals and 2-halobutenals should therefore be considered as candidate promutagens.

Ultrasound-induced intercellular space widening in fish epidermis.

Transmission electron microscopy was employed to determine the effects of therapeutic ultrasound (US) (I(sata) < or =2.2 W cm(-2), 3 MHz), sonicated at different angles and durations, on the external epithelia of fish skin. Sonication at 1.7 W cm(-2) (90 s), where the ultrasonic beam was perpendicular to the skin surface, produced minor intercellular space widening (ICSW), as well as the disruption of desmosomes connecting between the cells. Increasing the intensity to 2.2 W cm(-2) increased ICSW, the extent of which was positively correlated to the duration of exposure (30 to 90 s). Perpendicular sonication produced ICSW, almost exclusively between cells of the two outermost cell layers, parallel to the skin surface. Sonicating at 45 degrees (2.2 W cm(-2), 90 s) produced ICSW in deeper cell layers in the tissues, in which the spaces were at seemingly random orientations. Mucous cells and macrophages were also found to be damaged, as were apoptotic epidermal cells. The suggested mechanism for ICSW is the formation of transverse (shear) waves at the interface between the aquatic medium and the skin surface. The waves, which are damped out within a few cell layers, give rise to shear stresses that, in turn, cause strains that act to separate between cells and damage some of the relatively weaker cells.

Ultrasound-induced cavitation damage to external epithelia of fish skin.

Transmission electron microscopy was used to show the effects of therapeutic ultrasound (< or = 1.0 W/cm2, 1 MHz) on the external epithelia of fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

Collagen arrangement in hepatic granuloma in mice infected with Schistosoma mansoni: dependence on fiber radiation centers.

The collagen structure of isolated and in situ liver granuloma from Swiss Webster mice infected with Schistosoma mansoni was sequentially and three-dimensionally analyzed during different times of infection (early acute, acute, transitional acute-chronic, and chronic phases) by laser scanning confocal microscopy and electron scanning variable vacuum microscopy. The initial granuloma structure is characterized by vascular collagen residues and by anchorage points (or fiber radiation centers), from where collagenous fibers are angularly shed and self-assembled. During the exudative-productive stage, the self-assembly of these fibers minimizes energy and mass through continuous tension and focal compression. The curvature or angles between collagen fibers probably depends on the fibroblastic or myofibroblastic organization of stress fibers. Gradually, the loose unstable lattice of the exudative-productive stage transforms into a highly packed and stable architecture as a result of progressive compactness. The three-dimensional architecture of granulomas provides increased tissue integrity, efficient distribution of soluble compounds and a haptotactic background to the cells.

Reaching out to the African American community through innovative strategies.

PURPOSE/OBJECTIVES: To describe the University of Pittsburgh Cancer Institute's African American Cancer Program, including innovative strategies that were used, barriers that were encountered, an evaluation of each component, and future directions and implications. DATA SOURCES: Published articles, references from bibliographies, census data, personal contact, unpublished data. DATA SYNTHESIS: Cancer morbidity and mortality is higher among African Americans than Caucasians. The University of Pittsburgh Cancer Institute pilot-tested four interventions to increase awareness, provide education and early detection opportunities, and overcome barriers to cancer care among African Americans. CONCLUSION: Constant presence, cultural sensitivity, and repetition are necessary to overcome the barriers to increased awareness and behavioral changes in the African American community. A more formalized evaluation component is necessary to draw definitive conclusions. IMPLICATIONS FOR NURSING PRACTICE: To develop cancer prevention and education programs that meet the unique needs of African Americans, nurses must be aware of barriers and cultural differences.

Preliminary investigations of ultrasound induced acoustic streaming using particle image velocimetry.

Particle image velocimetry was used to investigate ultrasound-induced acoustic streaming in a system for the enhanced uptake of substances from the aquatic medium into fish. Four distinct regions of the induced streaming in the system were observed and measured. One of the regions was identified as an preferential site for substance uptake, where the highest velocities in proximity to the fish surface were measured. A positive linear relationship was found between the ultrasound intensity and the maximum streaming velocity, where a unitless geometric factor, specific to the system, was calculated for correcting the numerical relationship between the two parameters. The results are part of a comprehensive study aimed at improving mass transdermal administrations of substances (e.g. vaccines, hormones) into fish from the aquatic medium.