Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.     

Expression and function of CD4 in a murine T-cell hybridoma

The CD4 (T4) antigen was originally described as a phenotypic marker specific for helper T cells, and has recently been shown to be the receptor for the human immunodeficiency virus (HIV). Functional studies using monoclonal antibodies directed at CD4 and major histocompatibility complex (MHC) class II molecules led to the suggestion that CD4 binds to the MHC class II molecules expressed on stimulator cells, enhancing T-cell responsiveness by increasing the avidity of T cell-stimulator cell interaction and/or by transmitting a positive intracellular signal. But recent evidence that antibodies to CD4 inhibit T-cell responsiveness in the absence of any putative ligand for CD4 has been interpreted as suggesting that antibody-mediated inhibition may involve the transmission of a negative signal via the CD4 molecule instead. We have infected a murine T-cell hybridoma that produces interleukin 2 (IL-2) in response to human class II HLA-DR antigens with a retroviral vector containing CD4 cDNA. The resulting CD4-expressing hybridoma cell lines produce 6- to 20-fold more IL-2 in response to HLA-DR antigens than control cell lines. Furthermore, when antigen levels are suboptimal, the response of the cell lines is entirely CD4-dependent. The data presented here clearly demonstrate that CD4 can enhance T-cell responsiveness and may be crucial in the response to suboptimal levels of antigen.     

Role of corticosteroid-binding globulin in interaction of corticosterone with uterine and brain progesterone receptors

The central actions of the steroid hormone progesterone remain an enigma. However, there is no doubt that this hormone has a vital role in the control of sexual function and behaviour in many species, including man. Furthermore, progesterone may be involved in the premenstrual and postpartum syndromes. It would therefore be very useful to know the role and mechanism of action of progesterone in the brain. We now show that there are differences between progesterone receptors in brain and uterus, and possibly in the distribution of the serum progesterone-binding protein, corticosteroid-binding globulin (CBG), which may enter uterine but not brain cells.     

Predicting bankruptcy using recursive partitioning and a realistically proportioned data set

Auditors must assess their clients' ability to function as a going concern for at least the year following the financial statement date. The audit profession has been severely criticized for failure to ‘blow the whistle’ in numerous highly visible bankruptcies that occurred shortly after unmodified audit opinions were issued. Financial distress indicators examined in this study are one mechanism for making such assessments. This study measures and compares the predictive accuracy of an easily implemented two‐variable bankruptcy model originally developed using recursive partitioning on an equally proportioned data set of 202 firms. In this study, we test the predictive accuracy of this model, as well as previously developed logit and neural network models, using a realistically proportioned set of 14,212 firms' financial data covering the period 1981–1990. The previously developed recursive partitioning model had an overall accuracy for all firms ranging from 95 to 97% which outperformed both the logit model at 93 to 94% and the neural network model at 86 to 91%. The recursive partitioning model predicted the bankrupt firms with 33–58% accuracy. A sensitivity analysis of recursive partitioning cutting points indicated that a newly specified model could achieve an all firm and a bankrupt firm predictive accuracy of approximately 85%. Auditors will be interested in the Type I and Type II error tradeoffs revealed in a detailed sensitivity table for this easily implemented model. Copyright © 2000 John Wiley & Sons, Ltd.     

Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes

Human cluster-of-differentiation 1 (CD1) is a family of cell surface glycoproteins of unknown function expressed on immature thymocytes, epidermal Langerhans cells and a subset of B lymphocytes. Three homologous proteins, CD1a, b and c, have been defined serologically, and the CD1 gene locus on human chromosome 1 contains five potential CD1 genes. Analysis of the predicted amino-acid sequences of CD1 molecules reveals a low but significant level of homology to major histocompatibility complex (MHC) class I and class II molecules, and, like MHC class I molecules, CD1 molecules are associated non-covalently with beta 2-microglobulin. These structural similarities to known antigen-presenting molecules, together with the expression of CD1 on cells capable of antigen presentation, suggest a role for CD1 molecules in antigen recognition by T cells. Here we demonstrate the specific recognition of CD1a by a CD4-CD8- alpha beta T-cell receptor (TCR) expressing cytolytic T lymphocyte (CTL) line and the specific recognition of CD1c by a CD4-CD8- gamma delta TCR CTL line. The interaction of CD1-specific CTLs with CD1+ target cells appeared to involve the CD3-TCR complex, and did not show evidence of MHC restriction. These results suggest that for a subset of T cells, CD1 molecules serve a function analogous to that of MHC class I and II molecules.     

Convergent evolution of defensin sequence,structure and function

Defensins are a well-characterised group of small, disulphide-rich, cationic peptides that are produced by essentially all eukaryotes and are highly diverse in their sequences and structures. Most display broad range antimicrobial activity at low micromolar concentrations, whereas others have other diverse roles, including cell signalling (e.g. immune cell recruitment, self/non-self-recognition), ion channel perturbation, toxic functions, and enzyme inhibition. The defensins consist of two superfamilies, each derived from an independent evolutionary origin, which have subsequently undergone extensive divergent evolution in their sequence, structure and function. Referred to as the cis- and trans-defensin superfamilies, they are classified based on their secondary structure orientation, cysteine motifs and disulphide bond connectivities, tertiary structure similarities and precursor gene sequence. The utility of displaying loops on a stable, compact, disulphide-rich core has been exploited by evolution on multiple occasions. The defensin superfamilies represent a case where the ensuing convergent evolution of sequence, structure and function has been particularly extreme. Here, we discuss the extent, causes and significance of these convergent features, drawing examples from across the eukaryotes.     

Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America

Summary Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.Supported by U.S. Public Health Service (5-K6-GM-13981-17), National Cancer Institute (1R01-CA-14445-05 and N01-CP-5-5702), National Institute of Occupational Safety and Health (OH-00631-01), National Institute of Aging (AG-00158), Environmental Protection Agency (R804513-01-0), Swedish Medical Research Council grant 3371 and the St Paul Ramsey Medical Research and Education Foundation. R.B. Sothern and Jung-Keun Lee, Scientists, Chronobiology Laboratories, University of Minnesota provided valuable help.     

Trichoptera and other macroinvertebrates in springs of the Great Basin: species composition, richness, and distribution

Detailed surveys of aquatic invertebrates in 28 springs along the western border of the Great Basin were made using pan traps, emergence traps, black lights, and benthic sampling devices from 1994 to 1998. Although all macroinvertebrate groups were collected, caddisflies (Insecta: Trichoptera) were sampled most intensively. Fifty-eight species of caddisflies were collected from the 28 springs, with up to 18 species from a single spring. Although several springs had very similar physicochemical characteristics, none had identical trichopteran species composition. Using Wards minimum variance clustering technique, and with all macroinvertebrates identified to the lowest possible level, we found 3 taxa assemblages. These assemblages occurred in springs with the following physical conditions: (1) warm water (15.9° C), low elevation (1794 m); (2) cold water (8.5° C), mid-elevation (2334 m); and (3) cold water (6.6° C), high elevation (1794 m). Although the warm water group had a distinct assemblage of invertebrates (amphipods, gastropods, Trichoptera), distinct assemblages did not separate the 2 cold water groups. Discriminant analysis indicated that temperature, conductivity, alkalinity, and elevation were most responsible for discriminating group 1 from groups 2 and 3; temperature and elevation distinguished the latter 2 groups. Spring permanence, lack of disturbance, and cold water temperatures were the factors most responsible for explaining higher species richness of Trichoptera.