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At least 973 records · Page 54Linked to original sources

PubMed1990

Effect of naturally occurring nematode infections on growth performance of first-season grazing calves.

Liveweight of calves on 89 dairy farms was measured at the end of the grazing season and related per herd to the level of exposure to nematode infection during the grazing season. There were significant between-herd variations in antibody titres against Ostertagia spp., Cooperia spp. and Dictyocaulus viviparus as well as in pepsinogen values. All but six herds (93.1%) had gastrointestinal nematode infections, as measured by faecal egg counts in September. Faecal samples of 17 herds (19.3%) contained lungworm larvae in September. Liveweight of calves per herd deviated from -68.1 kg to +84.1 kg from the age-adjusted population mean after their first grazing season. Growth performance up to the time of liveweight measurements was significantly correlated negatively with several serological and parasitological parameters. Data could be fitted by means of both linear and segmented curvilinear regression. Antibody titre against Cooperia spp. and gastrointestinal nematode egg output measured in September accounted for 3.1% (P less than 0.10) and 6.7% (P less than 0.05), respectively, of the variation in growth performance among herds. Certain infection parameters, when combined, accounted for 9.2% of this variation; these were antibody titre against Cooperia spp. and larval counts for both gastrointestinal nematodes and lungworm. Adding certain management factors to these infection parameters resulted in a model explaining 27.6% of the observed variation in growth performance among herds. These factors were supplementary feeding, lungworm vaccination, anthelmintic treatment at housing, date of housing and herd age.

Age Factors↗

PubMed2004

Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes.

Beta-catenin plays essential roles in both cell-cell adhesion and Wnt signal transduction, but what precisely controls beta-catenin targeting to cadherin adhesive complexes, or T-cell factor (TCF)-transcriptional complexes is less well understood. We show that during Wnt signaling, a form of beta-catenin is generated that binds TCF but not the cadherin cytoplasmic domain. The Wnt-stimulated, TCF-selective form is monomeric and is regulated by the COOH terminus of beta-catenin, which selectively competes cadherin binding through an intramolecular fold-back mechanism. Phosphorylation of the cadherin reverses the TCF binding selectivity, suggesting another potential layer of regulation. In contrast, the main cadherin-binding form of beta-catenin is a beta-catenin-alpha-catenin dimer, indicating that there is a distinct molecular form of beta-catenin that can interact with both the cadherin and alpha-catenin. We propose that participation of beta-catenin in adhesion or Wnt signaling is dictated by the regulation of distinct molecular forms of beta-catenin with different binding properties, rather than simple competition between cadherins and TCFs for a single constitutive form. This model explains how cells can control whether beta-catenin is used independently in cell adhesion and nuclear signaling, or competitively so that the two processes are coordinated and interrelated.

Animals↗

PubMed1999

Selection for high and low virulence in the malaria parasite Plasmodium chabaudi.

What stops parasites becoming ever more virulent? Conventional wisdom and most parasite-centred models of the evolution of virulence suppose that risk of host (and, hence, parasite) death imposes selection against more virulent strains. Here we selected for high and low virulence within each of two clones of the rodent malaria parasite Plasmodium chabaudi on the basis of between-host differences in a surrogate measure of virulence--loss of live weight post-infection. Despite imposing strong selection for low virulence which mimicked 50-75% host mortality, the low virulence lines increased in virulence as much as the high virulence lines. Thus, artificial selection on between-host differences in virulence was unable to counteract natural selection for increased virulence caused by within-host selection processes. The parasite's asexual replication rate and number of sexual transmission forms also increased in all lines, consistent with evolutionary models explaining high virulence. An upper bound to virulence, though not the asexual replication rate, was apparent, but this bound was not imposed by host mortality. Thus, we found evidence of the factors assumed to drive evolution of increased virulence, but not those thought to counter this selection.

Animals↗

PubMed2000

Modeling the fission yeast cell cycle: quantized cycle times in wee1- cdc25Delta mutant cells.

A detailed mathematical model for the fission yeast mitotic cycle is developed based on positive and negative feedback loops by which Cdc13/Cdc2 kinase activates and inactivates itself. Positive feedbacks are created by Cdc13/Cdc2-dependent phosphorylation of specific substrates: inactivating its negative regulators (Rum1, Ste9 and Wee1/Mik1) and activating its positive regulator (Cdc25). A slow negative feedback loop is turned on during mitosis by activation of Slp1/anaphase-promoting complex (APC), which indirectly re-activates the negative regulators, leading to a drop in Cdc13/Cdc2 activity and exit from mitosis. The model explains how fission yeast cells can exit mitosis in the absence of Ste9 (Cdc13 degradation) and Rum1 (an inhibitor of Cdc13/Cdc2). We also show that, if the positive feedback loops accelerating the G(2)/M transition (through Wee1 and Cdc25) are weak, then cells can reset back to G(2) from early stages of mitosis by premature activation of the negative feedback loop. This resetting can happen more than once, resulting in a quantized distribution of cycle times, as observed experimentally in wee1(-) cdc25Delta mutant cells. Our quantitative description of these quantized cycles demonstrates the utility of mathematical modeling, because these cycles cannot be understood by intuitive arguments alone.

CDC2 Protein Kinase↗

PubMed2004

A neurodynamical cortical model of visual attention and invariant object recognition.

We describe a model of invariant visual object recognition in the brain that incorporates feedback biasing effects of top-down attentional mechanisms on a hierarchically organized set of visual cortical areas with convergent forward connectivity, reciprocal feedback connections, and local intra-area competition. The model displays space-based and object-based covert visual search by using attentional top-down feedback from either the posterior parietal or the inferior temporal cortex (IT) modules, and interactions between the two processing streams occurring in V1 and V2. The model explains the gradually increasing magnitude of the attentional modulation that is found in fMRI experiments from earlier visual areas (V1, V2) to higher ventral stream visual areas (V4, IT); how the effective size of the receptive fields of IT neurons becomes smaller in natural cluttered scenes; and makes predictions about interactions between stimuli in their receptive fields.

Attention↗

PubMed2003

The use of economic modeling to determine the hospital costs associated with nosocomial infections.

Hospital-associated infection is well recognized as a patient safety concern requiring preventive interventions. However, hospitals are closely monitoring expenditures and need accurate estimates of potential cost savings from such prevention programs. We used a retrospective cohort design and economic modeling to determine the excess cost from the hospital perspective for hospital-associated infection in a random sample of adult medical patients. Study patients were classified as being not infected (n=139), having suspected infection (n=8), or having confirmed infection (n=17). Severity of illness and intensive unit care use were both independently associated with increased cost. After controlling for these confounding effects, we found an excess cost of $6767 for suspected infection and $15,275 for confirmed hospital-acquired infection. The economic model explained 56% of the total variability in cost among patients. Hospitals can use these data when evaluating potential cost savings from effective infection-control measures.

Adult↗

PubMed1998

Utilization of an NF-ATp binding promoter element for EGR3 expression in T cells but not fibroblasts provides a molecular model for the lymphoid cell-specific effect of cyclosporin A.

Cyclosporin A (CsA) mainly exerts its immunosuppressive action by selectively inhibiting Ca2+/calcineurin-dependent gene transcription in lymphoid cells. A model explaining the tissue-specific effect of this drug on gene expression has not been established to date, since none of the known intracellular targets of CsA (e.g., cyclophilins, calcineurin, and NF-AT) is lymphoid cell specific. To investigate this issue, we performed a detailed comparative analysis of the promoter regulating the two-signal-dependent (Ca2+ ionophore plus phorbol myristate acetate [PMA]), CsA-sensitive expression of EGR3 in T cells and the one-signal-dependent (PMA), CsA-insensitive expression of EGR3 in fibroblasts. As a result, we identified a 27-bp promoter element functionally interacting with transcription factors NF-ATp and NF-ATc that is crucial for the CsA-sensitive expression of the EGR3 gene in T cells. In contrast, the same element was without function in fibroblasts, and other, CsA-insensitive promoter regions were found to be responsible for EGR3 gene expression in these cells. The inactivity of the 27-bp element in fibroblasts was apparently due to insufficient expression levels of NF-ATp, since overexpression of NF-ATp, but not NF-ATc, restored the two-signal phenotype and CsA sensitivity of EGR3 promoter induction in these cells. The differential usage of an NF-AT binding site explains the selective effect of CsA on EGR3 gene expression in T cells versus fibroblasts and may represent one of the basic mechanisms underlying the tissue specificity of CsA.

Base Sequence↗

PubMed1985

Interaction between heart as a pump and artery as a load.

For a better understanding of the functional roles of the heart as a pump system, an analogy with an industrial fluid-pump system is beneficial. In this paper, the use of the ventricular pressure-volume relationship was shown to provide one of the most useful descriptions of the heart as a pump system. This description included the pump function of the ventricle as well as the interrelation between cardiac mechanics and energetics. In describing the heart only as a pump, Thévenin's network model consisting of a source of pressure with a series source resistance (or impedance) is useful in analysing the complex interactions of the equilibrium mechanism for determining cardiac output and arterial pressure, and the matching conditions under the ventriculo-arterial coupling during the ejection period for a given set of ventricular and arterial system parameters. The analytical results using this model explained previous experimental results by other investigators. It was also suggested that the ventriculo-arterial-coupled system appears to be matched. From the engineering point of view, it is desirable also for the ventricle as a pump to behave under such an optimum matching condition for delivering a maximum power to the arterial load.

Blood Pressure↗

PubMed1987

[Mechanisms common to biological macromolecules and gels].

Functional Biological macromolecules arising from folding, cross-connection and solvation of long chain biopolymers forming three-dimensional networks may be regarded as Gels. Both involve identical internal competitive forces that are selectively influenced by external conditions and conspire to adjust conformations and modulate activities. In spite of important differences in size, chemical composition, polymer bonding, density and configuration, biological macromolecules indeed manifest some of the essential physical-chemical properties of gels when involved in equilibria and rate processes. This result represents a presumptive evidence for common underlying mechanisms in functional molecules and gels. Thus, the present and highly perfectible model explains why and how, depending on initial conditions, a system may respond differently to an external parameter, and similarly to different parameters. Moreover, the fact that any localized change in one of the competitive forces gives to a pressure in the system as a whole provides an explanation for the mechanism of the transmission of information.

Biopolymers↗

PubMed1983

The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves.

The atrophy of cutaneous (sural) and muscle (medial gastrocnemius) nerves proximal to a ligation were studied in cats for periods up to 9 months, using light and electron microscopy, conduction velocity measurements and computer simulations. As atrophy proceeds, nerve fibres become increasingly non-circular. Cross-sectional areas of axons and fibres (axon + myelin) were measured. The diameters of equivalent circles (having the same axon and fibre cross-sectional area) were then calculated. A linear relation was found between axon diameter and fibre diameter, but the slope decreased as atrophy continued. This indicates that the axon cross-sectional area decreases relatively more than the total fibre area. Reduction in conduction velocity correlates more closely with reduction in axon diameter than fibre (axon + myelin) diameter. The ratio of the inner (axon) perimeter to the outer (myelin) perimeter remains constant at or near the optimal value of 0.6 for conduction in all groups of fibres at all periods of atrophy. Furthermore, the thickness of the myelin remains constant for a given perimeter over the entire period of atrophy studied. This suggests that the number of turns of myelin and the length of each turn remain unchanged during peripheral nerve atrophy. A simple geometric model explains how this can occur without gaps developing between the axon and myelin or between the turns of myelin. The Frankenhaeuser-Huxley equations for conduction in myelinated nerve fibres predict changes in conduction velocity similar to those observed, if the axons atrophy without changes in myelin. The advantages of this mode of atrophy are discussed.

Animals↗

PubMed1999

Structural examination of autoregulation of multifunctional calcium/calmodulin-dependent protein kinase II.

Regulation of Ca(2+)/calmodulin-dependent protein kinase II is likely based on an auto-inhibitory mechanism in which a segment of the kinase occupies the catalytic site in the absence of calmodulin. We analyze potential auto-inhibitory associations by employing charge reversal and hydrophobic-to-charged residue mutagenesis. We identify interacting amino acid pairs by using double mutants to test which modification in the catalytic domain complements a given change in the auto-inhibitory domain. Our studies identify the core pseudosubstrate sequence (residues 297-300) but reveal that distinct sequences centered about the autophosphorylation site at Thr-286 are involved in the critical auto-inhibitory interactions. Individual changes in any of the residues Arg-274, His-282, Arg-283, Lys-291, Arg-297, Phe-293, and Asn-294 in the auto-inhibitory domain or their interacting partners in the catalytic domain produces an enhanced affinity for calmodulin or generates a constitutively active enzyme. A structural model of Ca(2+)/calmodulin-dependent protein kinase II that incorporates these interactions shows that Thr-286 is oriented inwardly into a hydrophobic channel. The model explains why calmodulin must bind to the auto-inhibitory domain in order for Thr-286 in that domain to be phosphorylated and why introduction of phospho-Thr-286 produces the important Ca(2+)-independent state of the enzyme.

Amino Acid Sequence↗

PubMed2002

Vapor/Solid chemisorption model for passive sampling of aldehydes.

The vapor-phase chemisorption isotherms of valeraldehyde (n-valeraldehyde; 1-pentanal) and acrolein (2-propenal) above the critical face velocity (7.5 cm/s) were investigated at 25 degrees C and 36 percent relative humidity (RH) for a passive air sampling pellet of 10 percent O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine hydrochloride (PFBHA) on Tenax TA solid sorbent (80/100 mesh). A dynamic air dilution system with syringe pumps generated the vapor concentrations and humidity for the exposure chamber. The O-oxime derivatives were desorbed with hexane for gas chromatographic analysis on a nonpolar capillary column and electron capture detection. The pellet capacity was about 30 micromoles. Adsorption of valeraldehyde was best fitted by a Langmuir or Brunauer-Emmett-Teller (BET) I model. That for acrolein was described best by a Dubinin-Radushkevich model. A microporosity model explained why all the classical isotherms described the chemisorption behavior. An activated extrinsic precursor was suggested to facilitate the addition reaction by production of a protonated intermediate formed by the transfer of a proton to the aldehyde from an activated reaction site consisting of at least 2 PFBHA molecules.

Adsorption↗

PubMed1996

Predicting sleep latency from the three-process model of alertness regulation.

This paper presents a modification of the quantitative "three-process model of alertness regulation" to predict sleep latency in connection with irregular sleep/wake patterns. This model uses a circadian and a homeostatic component (sleep loss) that are summed to yield predicted alertness (on a scale of 1 to 20) across a specified time span. The timing of sleep from two studies of irregular sleep were used as input to the model. The predicted alertness at bedtime was regressed on empirical sleep latency from two studies. The maximum R2 (0.88) was reached for an exponential function, with the model acrophase set to 2048. The predictions were cross validated on another set of sleep latency data from an irregular sleep study and a maximum R2 of 0.65 was obtained. In both studies, the prediction from the model explained more variance that did self-rated alertness at bedtime. Cross validation was also carried out successfully with published data from two studies of shift work. It was concluded that sleep latency on irregular schedules may be predicted with accuracy from knowledge of the prior sleep/wake pattern. This may have practical consequences for rest/activity management.

Adult↗

PubMedDate not supplied

Ammonia emissions from swine houses in the southeastern United States.

Ammonia (NH3) from confined animal feeding operations is emitted from several sources including lagoons, field applications, and houses. This paper presents studies that were conducted to evaluate NH3 emissions from swine finisher and sow animal houses in the southeastern USA. Management and climate variables including animal weight, feed consumption, housing gutter water temperature, total time fans operated per day, house air temperature, house ambient NH3 concentration, and animal numbers were measured to determine their individual and combined effect on NH3 emissions. Ammonia emissions varied on daily and seasonal bases with higher emissions during warmer periods. For finishers, the summertime housing emissions on a per-animal basis were 2.4 times higher than wintertime (7.0 vs. 3.3 g NH3 animal(-1) d(-1)) or 3.2 times higher when compared on an animal unit (AU) basis (1 AU = 500 kg) because of climate and animal size differences between measurement periods. For summertime, the emission factor for the finishing pigs was 7.8 times higher than for sows on an animal basis and 25.6 times higher on an AU basis. Simple models were developed for housing emissions based on (i) all measured factors that were independent of each other and (ii) on three commonly measured management factors. The two models explained 97 and 64%, respectively, of variations in emissions. Ammonia emissions were found to be somewhat less than other studies on the same type housing due to more representative housing concentration measurements and calibration of exhaust fans; thus, emission factors for these type houses will be less than previously thought.

Air Pollutants↗

PubMed1994

Mutations in demyelinating peripheral neuropathies support molecular model of myelin P0-glycoprotein extracellular domain.

Homophilic interactions of the major integral membrane protein of peripheral nerve myelin, P0-glycoprotein, are thought to mediate membrane adhesion and compaction. Molecular modeling of its extracellular domain (P0-ED), based on its resemblance to an immunoglobulin variable domain and on X-ray diffraction measurements of inter-membrane spacings of myelin, has suggested which amino acid sidechains may be involved in the homophilic adhesion. Recently identified point-mutations in the human P0 gene result in amino acid substitutions in P0 protein and correlate with demyelinating motor and sensory neuropathies. The molecular model explains how these changes result in disrupted P0-P0 interactions; indicates how compensatory changes in amino acids, as occur in P0-ED of other species, preserve normal homophilic interactions; and predicts what other residue substitutions might underlie additional cases of demyelinating neuropathies.

Animals↗

PubMed2003

Predictors of reported consumption of low-nutrient-density foods in a 24-h recall by 8-16 year old US children and adolescents.

The purpose of this study was to develop an explanatory model to predict the number of low-nutrient-density (LND) foods reported in a 24-h recall by US children and adolescents using data from the third National Health and Nutrition Examination Survey. The reported number of LND foods was estimated from 24-h dietary recall data for 8-16 year old respondents (n=4137; 2024 males and 2113 females). The LND foods included--baked and dairy desserts, sweeteners, salty snacks, visible/discretionary fat, and miscellaneous. The predictive ability of socio-demographic, family, weight/dieting related, life-style or food consumption related subject characteristics was determined using multiple linear regression analyses. The strongest independent negative predictor of the reported number of LND foods was the amount of nutrient-dense foods from the five major food groups. In addition, number of eating occasions reported was a significant independent positive predictor, and the weekly frequency of consuming a complete school lunch was a significant independent negative predictor of the reported number of LND foods. These models explained approximately 55% of the variance in LND food reporting in both males and females. Socio-demographic, family, body weight, or lifestyle characteristics contributed little to predicting the number of LND foods reported in a 24-h recall.

Adolescent↗

PubMed1989

Model for population distributions of lymphocyte-target cell conjugates.

A quantitative model for the population distributions of the different types of conjugates formed between cytotoxic T lymphocytes and target cells has been developed. The comparison of the theoretical predictions with data of the literature reveals that the transit populations among the different types of conjugates depends on the lymphocyte-to-target ratio, R, and two constants, k and k1. These constants (where k greater than k1) govern, respectively, the transit populations among conjugates of the type LTi (LTn----LTn-1----...LT), and among LjT conjugates (LT----L2T----...----LmT). We have found that high ratios are necessary to obtain conjugates where multiple T lymphocytes are bound to one target cell, and that under these conditions the predominant conjugate, LjT, varies according to j = 1 + k1R. Conversely, for low values of R the predominant population is of the type LTi, where i also shows a linear dependence on R. Our model explains also why the conjugate LT is normally the predominant population under the experimental conditions reported in the literature. A discussion of the influence exerted by the population distributions of lymphocyte-target cell conjugates on the kinetic of the lytic process for these kinds of effector-target systems has also been made.

Immunity, Cellular↗

PubMed2002

The search for local native-like nucleation centers in the unfolded state of beta -sheet proteins.

An approach involving the systematic computational conformational analysis of all overlapping hexapeptide segments in the protein sequence has found fragments with the higher than average propensity to adopt the native-like three-dimensional structure and other regular nonrandom structures in the unfolded states of four beta-sheet proteins, namely IFABP (intestinal fatty acid-binding protein), ILBP (ileal fatty acid-binding protein), CRABP I (cellular retinoic acid-binding protein), and CRBP II (cellular retinal binding protein). The native three-dimensional structures of these four proteins are very similar even though they possess as little as approximately 30% sequence similarity. The computational results were validated by comparison with the experimental data of the heteronuclear sequential quantum correlation NMR spectroscopy obtained earlier for IFABP at high urea concentrations. On this basis, a molecular model of the unfolded state of IFABP has been developed. The model presumes a dynamic equilibrium between various nonrandom structures (including the native-like structure) and random coil in the local segments of the protein sequence. The model explains experimental observations obtained earlier for folding of several mutants of IFABP, as well as the observed differences in molecular mechanisms of folding for the four beta-sheet proteins. Because the computational approach itself does not employ any experimentally derived information in advance, it is not necessarily limited to the beta-sheet proteins.

Amino Acid Sequence↗