Basis For Differences In Susceptibility Research Articles

Environmental stress tolerance and immune response for the small abalone hybrids

Recently, mass mortality affected the cultured small abalone, Haliotis diversicolor diversicolor, which was the dominant cultured abalone species in southern China. Prior studies revealed that survivorship varied significantly between different stocks and crosses. However, the immunological basis for differences in susceptibility has not been well understood to date. Herein, low temperature, air exposure tolerance tests, and pull-off force measurement were assessed in the three groups (Japan, Taiwan, and their Hybrid stock). The results showed that the critical thermal minimum (CTMin) at 50% was 15.6 °C for the Taiwan stock, 12.1 °C for the Japan stock, and 13.2 °C for the Hybrid stock. Upon air exposure challenge, 100% abalones from the Taiwan group died after 8 h at 24 °C, while the survival rate in the Japan and Hybrid groups were 37.8% and 29.4%, respectively. The detachment stress for the Japan group was 42.3 kPa, which was 2.78-fold and 1.43-fold higher compared to the Taiwan and Hybrid groups, respectively. Variation in susceptibility to disease may be based on the effectiveness of the innate immune responses. Therefore, total hemocyte count, phagocytosis, respiratory burst, superoxide dismutase activity, acid phosphatase activity, alkaline phosphatase activity, and myeloperoxidase activity were determined for the healthy abalones in each group. Positive mid-parent heterosis on immunological parameters was consistent with the prior knowledge on the positive mid-parent heterosis for survival rate, which indicated the improvement on immune reaction and disease resistance through hybridization methods. The current study will be useful in efficient design of breeding programs for the development of sustainable abalone aquaculture.

The Office of Health Assessment and Translation: A Problem-Solving Resource for the National Toxicology Program

The Office of Health Assessment and Translation: A Problem-Solving Resource for the National Toxicology Program

Inhibitory effect of hydroxycinnamic acids on Dekkera spp.

Simple phenolic components of wine, hydroxycinnamic acids (HCAs) are known to have antimicrobial properties. This study sought to determine the potential of ferulic acid as an antifungal agent for the control of Dekkera. Growth was inhibited by all HCAs examined in this study, with ferulic acid being the most potent at all concentrations. In the presence of ethanol, the inhibitory effects of ferulic acid were amplified. Scanning electron microscopy images reveal cellular damage upon exposure to ferulic acid. Thus, manipulation of ferulic acid concentrations could be of industrial significance for control of Dekkera and may be the basis for differences in susceptibility of wines to Dekkera spoilage.

Differences in mortality, growth, lysozyme, and Toll-like receptor gene expression among genetic groups of catfish exposed to virulent Edwardsiella ictaluri

Survivorship to ESC (enteric septicemia of catfish) varies among and within strains of commercially raised catfish, however the immunological basis for differences in susceptibility is not well-understood. We assessed the effect of pathogen challenge with Edwardsiella ictaluri on five genetic groups of catfish by measuring both phenotypic response (mortality, pathogen levels, specific growth rate), and three measures of immune response, including lysozyme activity and mRNA expression of two toll-like receptors (TLR3 and TLR5). Both mortality and pathogen loads, in addition to non-specific immune response, consistently ranged from the least susceptible Blue catfish (24%, 3.4 × 10 2 ± 9.3 × 10 1 cell-equivalents/mg, 13.2 ± 3.2 U/mL tissue, respectively) to the most susceptible 103 channel catfish (65%, 1.1 × 10 4 ± 6.4 × 10 3 cell-equivalents/mg tissue, 67.3 ± 28.7 U/mL, respectively). Similarly, specific growth rate was reduced in exposed fish, compared to non-exposed controls, only in the most susceptible genetic groups ( P = 0.0051). Trends in mRNA expression levels were apparent in each tissue type for both genes. In kidney, differences were evident in expression of both TLR3 and TLR5 mRNA between strains early and late in challenge ( P < 0.01). TLR5 mRNA showed significant downregulation in all strains on days 1 and 4 ( P = 0.0001). In spleen, all strains had elevated levels of TLR3 ( P = 0.0050) and TLR5 mRNA ( P < 0.0001) only 1 day post-exposure. In stomach, only one strain (103 × RR) showed upregulation ( P = 0.0063) throughout challenge. The relationship of phenotypic (mortality and growth) and immune responses measured here, suggests that variation in susceptibility to ESC is a function of differences in innate immune response. Understanding these differences will be crucial for enhancing the immune system through selective breeding and in developing disease management protocols for channel catfish.

Resistance to malignant catarrhal fever in American bison (Bison bison) is associated with MHC class IIa polymorphisms

The Rhadinovirus ovine herpesvirus-2 (OvHV-2) is the most common causative agent of malignant catarrhal fever (MCF) in clinically susceptible ruminants including cattle and bison. American bison (Bison bison) are highly susceptible to clinical MCF. Nevertheless, approximately 20% of bison on ranches or in feedlots become infected with the virus without developing clinical disease. Defining the genetic basis for differences in susceptibility between bison could facilitate development of improved control strategies for MCF. One genetic region that influences susceptibility to infectious diseases is the major histocompatibility complex (MHC). In this study, a Bison bison (Bibi) DRB3 oligonucleotide microarray was used to type 189 bison from 10 herds where MCF outbreaks had occurred. Binary logistic regression was used to classify DRB3 alleles as resistant (R), susceptible (S) or neutral (N). Animals were reclassified using six DRB3 genotype categories: N/N, N/R, N/S, R/S, R/R and S/S. Analysis of homogeneity across herds showed that there was a herd effect. Consequently, a penalized logistic regression model was run with herd and genotype categories as the explanatory variables. The R/R genotype was associated with resistance to MCF (P = 0.0327), while the S/S genotype was associated with clinical MCF (P = 0.0069). This is the first evidence that MHC class IIa polymorphism is associated with resistance or susceptibility to OvHV-2-induced MCF.

Variations in Equid SLC11A1 (NRAMP1) Genes and Associations with Rhodococcus equi Pneumonia in Horses

Rhodococcus equi is an important intracellular pathogen of horses, most commonly causing chronic, suppurative bronchopneumonia in foals. Although most foals likely are exposed to environmental R equi within the 1st few days of life, only some develop R equi pneumonia, and the basis of differences in susceptibility among foals currently is unknown. In this study, we investigated solute carrier family 11 member 1 (SLC11A1) gene sequences in the 5' untranslated region, exon 1, and a portion of intron 1 for variations in 3 equid species (horse, donkey, zebra) and compared variants within 3 independent horse breeding farms for associations with R equi pneumonia by use of an age‐matched case‐control design. Seven novel variants in the 5' untranslated region were identified as specific for one or both of the non‐horse equid species sampled. In addition, a single novel horse variant in the 5' untranslated region, ‐57C/T, was identified in 4 breeds. The ‐57C/T variant was found on 2 of the 3 farms with endemic R equi pneumonia, representing 2 different horse breeds. Significant allelic and genotypic associations with susceptibility to R equi pneumonia were observed for the ‐57C/T variant in foals from these farms. Although the functional impact of this novel variant remains to be determined, this study represents an important step in our understanding of natural resistance to R equi foal pneumonia and other intracellular bacterial diseases affecting equids.

Variations in Equid SLC11A1 (NRAMP1) Genes and Associations with Rhodococcus Equi Pneumonia in Horses

Rhodococcus equi is an important intracellular pathogen of horses, most commonly causing chronic, suppurative bronchopneumonia in foals. Although most foals likely are exposed to environmental R. equi within the 1st few days of life, only some develop R. equi pneumonia, and the basis of differences in susceptibility among foals currently is unknown. In this study, we investigated solute carrier family 11 member 1 (SLC11A1) gene sequences in the 5' untranslated region, exon 1, and a portion of intron 1 for variations in 3 equid species (horse, donkey, zebra) and compared variants within 3 independent horse breeding farms for associations with R. equi pneumonia by use of an age-matched case-control design. Seven novel variants in the 5'untranslated region were identified as specific for one or both of the non-horse equid species sampled. In addition, a single novel horse variant in the 5'untranslated region, -57C/T, was identified in 4 breeds. The -57C/T variant was found on 2 of the 3 farms with endemic R. equi pneumonia, representing 2 different horse breeds. Significant allelic and genotypic associations with susceptibility to R. equi pneumonia were observed for the -57C/T variant in foals from these farms. Although the functional impact of this novel variant remains to be determined, this study represents an important step in our understanding of natural resistance to R. equi foal pneumonia and other intracellular bacterial diseases affecting equids.

Accounting for susceptibility in risk assessment: current practice and new directions

Differences in susceptibility between individuals can lead to variability in response to chemical exposures which in turn modify the risk of illness. As a means of exploring the basis for such differences in susceptibility, a project was undertaken to determine what data were available on the range of response variability for several health effects: neurotoxicity, reproductive/developmental toxicity, pulmonary toxicity, and cancer. In addition, modeling approaches for characterizing response variability were examined and evaluated. The main goal of this effort was to determine whether human response variability was adequately accounted for in the current risk assessment procedures for human health effects. The conclusions of the project were that few data are available, both because variability has rarely been the primary focus of study, and because data are not usually reported in such a way that response variability can be determined. Several recommendations were made to facilitate better characterization of interindividual variability, including the study of variability in available human data (e.g. the NHANES database) and allowing greater access to raw data from epidemiologic studies. In addition, the identification of relevant biomarkers, improved understanding of sources of variability, interaction of chemical effects with other exposures or pre-existing disease, and retrospective evaluations of risk assessments were recommended. It is hoped that these recommendations will stimulate research on susceptibility and response variability and encourage the reporting of data in a way that facilitates analysis of interindividual variability in response.

Molecular basis for differences in susceptibility to toxicants: introduction

Many toxicants depend upon metabolism for their elimination and/or conversion to the toxic species. As a consequence, differences in metabolism can have a profound influence on interspecies and interindividual susceptibility to toxicity. Until relatively recently, the molecular basis for such differences were not known. However, over the past decade and a half, our understanding of the factors controlling the expression and regulation of the enzymes of drug metabolism has increased dramatically. Thus, the molecular basis of the common polymorphisms of drug metabolism in man, in CYP2D6 (debrisoquine 4-hydroxylase) and NAT2 (arylamine N-acetyltransferase) has been determined, and considerable progress has been made in elucidating the regulatory control of inducible enzymes such as CYP1A1 and CYP4A1. The number of drug metabolising enzymes subject to genetic polymorphism in man is not known, but rare genetic differences in enzymes such as epoxide hydrolase are increasingly being implicated in susceptibility to toxicants previously attributed to idiosyncrasy Indeed, the whole concept of idiosyncrasy in reactions to toxicants is being rendered obsolete by such advances. As information on the basis of differences in susceptibility accrues, the challenge is to apply this knowledge in identifying the “at risk” population. Although much progress has been made in this area, there are still many unanswered questions. What controls the tissue, and indeed cell, selective expression of some enzymes of drug metabolism? What is the molecular basis of species differences in specificity? And most importantly, what factors beyond metabolism are involved in determining susceptibility, and how do these interact with differences in metabolism?

Molecular basis for differences in susceptibility to coal workers' pneumoconiosis

It is generally accepted that there are differences among workers in susceptibility towards the effects of mineral dusts such as silica, coal dust and asbestos. Basic research continues to find new factors involved in the process of pulmonary fibrosis caused by these minerals. In this paper, two hypotheses implicitly generated by recent findings were tested in two case-control studies among coal miners: generation of tumour necrosis factor (TNF) by blood monocytes of miners with coal workers' pneumoconiosis (CWP) and serum type III procollagen peptide (PIIIP) in CWP. Our data indicate that both parameters can be used as biological markers for early diagnosis of CWP. A follow-up study is described in which the predictive power of increased TNF release and serum PIIIP as risk factor to develop lung fibrosis will be assessed.