Development and use of probability models: The industry perspective

Summary In the processed meat industry, food safety and microbiological shelf life issues lend themselves to the use of probability modeling. Our research concentrated on predicting the effectiveness of sodium lactate as an antibotulinal agent in vacuum packaged, uncured and cured turkey breast model systems. In uncured turkey breast containing 1.4% NaCl, 0.3% Na phosphate, and 0–3% Na lactate, the antibotulinal effect of sodium lactate can be predicted using the following model: Days to toxicity = 3.13+0.39(Na lactate)². Using cured turkey breast with 0.3% Na phosphate, 0.2% sucrose, 0–3% Na lactate, the time to toxicity can be predicted from the following model: Days to toxicity = 1.69+4.88(NaCl)–11.16(Na lactate)+7.23(Na lactate)². Probability models have also been developed to predict the refrigerated shelf life of specific processed meat products. The usefulness of the predictive modeling for food safety and quality in the food industry will also be discussed.This paper was presented at The International Conference on the Application of Predictive Microbiology and Computer Modeling Techniques to the Food Industry, April 12–15 1992, Hyatt Regency Hotel, Tampa, FL, USA.     

Surveying nonvisual arrestins reveals allosteric interactions between functional sites

Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell-signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modeling (ANM) together with our covariance compliment techniques to survey all the available structures of the nonvisual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain β-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes.     

Recognition of errors in three-dimensional structures of proteins

A major problem in the determination of the three-dimensional structure of proteins concerns the quality of the structural models obtained from the interpretation of experimental data. New developments in X-ray crystallography and nuclear magnetic resonance spectroscopy have acceleratedd the process of structure determination and the biological community is confronted with a steadily increasing number of experimentally determined protein folds. However, in the recent past several experimentally determined protein structures have been proven to contain major errors, indicating that in some cases the interpretation of experimental data is difficult and may yield incorrect models. Such problems can be avoided when computational methods are employed which complement experimental structure determinations. A prerequisite of such computational tools is that they are independent of the parameters obtained from a particular experiment. In addition such techniques are able to support and accelerate experimental structure determinations. Here we present techniques based on knowledge based mean fields which can be used to judge the quality of protein folds. The methods can be used to identify misfolded structures as well as faulty parts of structural models. The techniques are even applicable in cases where only the C_α trace of a protein conformation is available. The capabilities of the technique are demonstrated using correct and incorrect protein folds. © 1993 Wiley-Liss, Inc.     

Short communication: Variability of response to feed restriction in lactating Charolais cows

Involuntary temporary feed restriction on commercial cattle is likely to become more frequent with forage shortages in the context of climate change. If general consequences of feed restriction have been the subject of an abundant scientific literature, focus on the inter-individual variability of response is scarce. Here, we explore the response profile in terms of BW, body condition score, milk production, calf weight and cyclicity resumption of 293 lactations from 169 Charolais cows during a winter feed restriction in early lactation and its subsequent recovery at grazing using a principal component analysis followed by a hierarchical clustering on principal component. Results show a very continuous range of response profiles that was divided into three clusters: one with light animals having an intermediate response in terms of milk production and body maintenance, one with animals prioritising body maintenance and cyclicity resumption over milk production and calf weight, and the last one with animals prioritising milk production and calf weight over the rest. Among the animals performing more than one lactation, 57% remain in the same cluster on two successive lactations. This work highlights that an average group response to feed restriction may hide various resilience individual profiles. Further studies are required to determine the existence of a genetic component as well as the consequences of not taking this phenomenon into consideration with the regular use of feed restriction in commercial farms.     

Low‐dose linearity: The rule or the exception?

In 1976, Crump, Hoel, Langley, and Peto described how almost any dose‐response relationship for carcinogens becomes linear at low doses when background cancers are taken into account. This has been used, by the U.S. Environmental Protection Agency, USEPA, as partial justification for a regulatory posture that assumes low‐dose linearity, as is illustrated by a discussion of regulation of benzene as a carcinogen. The argument depends critically on the assumption that the pollutant and the background proceed by the same biological mechanism. In this paper we show that the same argument applies to noncancer end points also. We discuss the application to a number of situations: reduction in lung function and consequent increase in death rate due to (particulate) air pollution; reduction in IQ and hence (in extreme cases) mental deficiency due to radiation in utero; reduction of sperm count and hence increase in male infertility due to DBCP exposure. We conclude that, although the biological basis for the health effect response is different, in each case low‐dose linearity might arise from the same mathematical effect discussed by Crump et al. (1976). We then examine other situations and toxic end points where low‐dose linearity might apply by the same argument. We urge that biologists and chemists should concentrate efforts on comparing the biological and pharmacokinetic processes that apply to the pollutant and the background. Finally, we discuss some public policy implications of the possibility that low dose linearity may be the rule rather than the exception for environmental exposures.     

Internal rhythms in humans

Human physiology and behavior are characterized by a daily internal temporal dimension. This so-called circadian rhythmicity is present for almost all variables studied to date, persists in the absence of external cycles, and is synchronized to the external 24-h world by an internally generated circadian rhythm of light sensitivity. The light-sensitive circadian pacemaker, presumably also in humans located in the suprachiasmatic nucleus of the hypothalamus, drives the endogenous circadian component of rhythmicity for a number of variables including plasma melatonin, alertness, sleep propensity and sleep structure. Overt rhythmicity and the consolidation of vigilance states are generated by a fine-tuned interaction of this circadian process with other regulatory processes such as sleep homeostasis.     

Enhancement of the light-triggered electrical response in plant cells following their de-energization with uncouplers

Light-triggered membrane potential changes in cells of a liverwort Anthoceros are greatly enhanced by the ionophorous uncouplers nigericin and monesin. Stimulation of the light-triggered electrical response (LTER) by nigericin occurred concomitantly with inhibition of a slow decline in the chlorophyll fluorescence, which suggests that the transmembrane pH gradient in thylakoids is not essential for generation of LTER at the plasma membrane. The extent of monensin-stimulated LTER remained high under a diminished driving force for the ionophore-induced proton-cation exchange across the plasma membrane (elevation of the external Na⁺ concentration from 1 to 50 m M ), which indicates that energy uncoupling in chloroplasts is more related to the electric response enhancement than the induction of the H⁺/K⁺(Na⁺) exchange at the plasma membrane. Enhancement of LTER by ionophores occurs in parallel with stimulation of light-triggered pH changes (alkalinization) in the vicinity of the cell surface, which suggests an association of trans-membrane H⁺ fluxes with LTER. The results are consistent with the hypothesis that illumination produces a temporary inhibition of the plasma membrane H⁺ pump with a subsequent activation of gated channels and transient rapid depolarization of the cell.     

Growth responses of some soil fungi to spatially heterogeneous nutrients

Abstract The natural nutritional environments of most fungi are spatially non-uniform, yet the majority of studies of fungal growth take no account of this fact. An experimental system is described which permits the growth responses of eucarpic fungi to heterogeneously distributed nutrient resources to be studied. The system comprises tesselations of agar tiles of contrasting nutrient status separated by air gaps. Growth responses in such systems of Alternaria alternata, Mucor sp., Phoma foveata , Rhizoctonia solani and Trichoderma viride are described. Generally, the growth of the fungi reflected the nutrient status of the underlying substrate. There was evidence for growth in low-nutrient tiles being greater when high-nutrient tiles were included in the tessellation. Reproductive structures tended to be formed only in low nutrient tiles with Trichoderma and Rhizoctonia and only high nutrient tiles with Alternaria . Growth responses of Rhizoctonia were strongly asymmetric in nutritionally symmetric, but heterogeneous, tesselations. The consequences of the observations for fungal growth in heterogeneous environments such as soil is discussed.     

The porcine intestinal receptor for Escherichia coli K88ab,K88ac: regional localization on chromosome 13 and influence of IgG response to the K88 antigen

The loci encoding the porcine intestinal receptors for Escherichia coli K88ab and K88ac (K88abR and K88acR) were firmly assigned to chromosome 13 by linkage analysis using a three-generation pedigree. The linear order of these loci and seven other markers on chromosome 13 was determined by multipoint analyses. The K88abR and K88acR loci were tightly linked with the K88abR locus localized 7·4 cM (sex average) proximal to the transferrin locus. The results, together with previous reports from two other groups, provide an unequivocal assignment of the K88 receptor loci to chromosome 13, and reject a previous assignment to chromosome 4. Pigs possessing the receptor had a slightly higher specific IgG response to the K88 antigen after an intramuscular immunization with an E. coli vaccine.