Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.     

Candidate cis-elements for human renin gene expression in the promoter region

The regulation of renin gene expression, the rate‐limiting enzyme of the system, is thought to be fundamental to the total system. Previously, we mapped six putative cis‐elements in the promoter region of the human renin gene with nuclear proteins from human chorionic cells and human renal cortex by DNase I protection assay (footprint A–F). Each footprint contains Ets motif like site (A), HOXñPBX recognition sequence (B), unknown sequence as DNA binding consensus (C), CRE (D), COUP‐TFII (ARP‐1) motif like site (E), and AGE3 like site (F). Footprint D has been characterized by means of functional studies as the genuine human renin gene CRE interacting with CREB in cooperation with the site of footprint B. To obtain further clues to the specific expression in the promoter region, these putative cis‐elements were conducted to a consensus‐specific binding assay to compare renin‐producing and non‐renin‐producing cells by EMSA and electromobility super‐shift assay. Different sequence‐specific DNA/protein binding was obtained among the different cell lines with footprint B site, with COUP‐TFII (ARP‐1) motif like site and possibly with footprint F site. The results implicate these putative cis‐elements and each corresponding trans‐factor in the specific expression of the human renin gene in the promoter region. Further functional characterization of these elements would provide important data for a better understanding of human renin gene expression. © 2004 Wiley‐Liss, Inc.     

When random sampling does not work: standard design falsely indicates maladaptive host preferences in a butterfly

In experiments that investigate species' interactions, individuals are often chosen at random to represent their populations. However, this practice can generate misleading results when individuals of different species do not interact at random. We illustrate this effect by examining oviposition preferences of Euphydryas aurinia butterflies from three populations using three different plant genera. We first offered each insect a randomly chosen member of its own host population and a foreign host ( Succisa pratensis ) not present in the insect's habitat. The butterflies uniformly preferred the foreign Succisa over their own hosts. Preferences were apparently maladaptive because insects wasted time searching for a nonexistent plant. We repeated the experiment using individual hosts that had naturally received eggs in the field. The overall preference for Succisa and the appearance of maladaptation both disappeared. In the original experiments, our random choice of experimental host individuals had combined with strong within-species discrimination by the butterflies and with overlap of acceptability between host species to obscure the true nature of host preference.     

Effects of prescribed fire on an ant community in Florida pine savanna

Abstract.  1. The effects of prescribed fire on ant community structure were examined in a regenerating longleaf pine savanna in Florida, U.S.A. The presence of ants on 20, 10 × 10 m plots was determined by baiting every 1–3 months from 18 months before a fire until 6 months afterwards.
2. Expected species richness (based on rarefaction) and species density 6 months post-fire were significantly lower than for the same month (September) 6 months before the fire.
3. Cluster analysis revealed that the effects of fire were far less important predictors of ant community structure than seasonality and unexplained inter-annual variation. Thus, overall, the impacts of fire were relatively minor and short term at the community level.
4. Different functional groups of ants (as defined by Andersen, 1997) responded to fire in strikingly different ways. Generalised Myrmicinae (e.g. Pheidole spp., Monomorium viride ) were affected more severely by fire than were the other functional groups. In contrast, the dominant Dolichoderinae ( Forelius pruinosus ) exhibited a large increase after the fire and seemed to be responsible for the decline in abundance of several species.
5. A strong negative correlation between F. pruinosus and other groups of ants immediately after the fire suggested more intense competition among ants at that time. Six months post-fire, the abundance of F. pruinosus decreased markedly and the abundance of other species rebounded.
6. The rapid post-fire recovery of the ant community probably reflects adaptations of ants to a chronic fire regime.     

Ultrasound-Derived Abdominal Muscle Thickness Better Detects Metabolic Syndrome Risk in Obese Patients than Skeletal Muscle Index Measured by Dual-Energy X-Ray Absorptiometry

Sarcopenia has never been diagnosed based on site-specific muscle loss, and little is known about the relationship between site-specific muscle loss and metabolic syndrome (MetS) risk factors. To this end, this cross-sectional study aimed to investigate the relationship between site-specific muscle size and MetS risk factors. Subjects were 38 obese men and women aged 40–82 years. Total body fat and lean body mass were assessed by whole-body dual-energy X-ray absorptiometry (DXA) scan. Muscle thickness (MTH) was measured using B-mode ultrasound scanning in six body regions. Subjects were classified into general obesity (GO) and sarcopenic obesity (SO) groups using the threshold values of one standard deviation below the sex-specific means of either MTH or skeletal muscle index (SMI) measured by DXA. MetS risk score was acquired by standardizing and summing the following continuously distributed variables: visceral fat area, mean blood pressure, HbA1c, and serum triglyceride / high density lipoprotein cholesterol, to obtain the Z-score. Multiple regression analysis revealed that the MetS risk score was independently associated with abdominal MTH in all subjects, but not with MTH in other muscle regions, including the thigh. Although HbA1c and the number of MetS risk factors in the SO group were significantly higher than those in the GO group, there were no significant differences between GO and SO groups as defined by SMI. Ultrasound-derived abdominal MTH would allow a better assessment of sarcopenia in obese patients and can be used as an alternative to the conventionally-used SMI measured by DXA.     

4,5-Disubstituted-1,3-oxazolidin-2-imine derivatives: a new class of orally bioavailable nitric oxide synthase inhibitor

In our search for a novel class of inducible nitric oxide synthase (iNOS) inhibitors, 1,3-oxazolidin-2-imine was found to weakly inhibit iNOS. Further modifications of this compound resulted in a remarkable increase in both the in vivo and in vitro inhibitory activity and selectivity for iNOS.     

Modelling ontogenetic changes of nitrogen and water content in lettuce

BACKGROUND AND AIMS: It is well established that the nitrogen content of plants, including lettuce, decreases with time. It has also been observed that water content of lettuce increases between planting and harvest. This paper is an attempt at modelling these observations. METHODS: An existing dynamic model (Nicolet), designed to predict growth and nitrate content of glasshouse lettuce, is modified to accommodate the ontogenetic changes of reduced-nitrogen and water contents (on a dry matter basis). The decreasing reduced-N content and the increasing water content are mimicked by dividing the originally uniform plant into 'metabolically active' tissue and 'support' tissue. The 'metabolic' tissue is assumed to contain a higher nitrogen content and a lower water content than the 'support' tissue. As the plants grow, the ratio of 'support' to 'metabolic' tissue increases, resulting in an increased mean water content and a decreased reduced-N content. Simulations with the new model are compared with experimental glasshouse data over four seasons. KEY RESULTS: The empirical linear relationship between water and reduced-N contents, matches, to a good approximation, the corresponding relationship based on the model. The agreement between the two makes it possible to effectively uncouple the estimation of the 'ontogenetic' parameters from the estimation of the other parameters. The growth and nitrate simulation results match the data rather well and are hardly affected by the new refinement. The reduced-N and water contents are predicted much better with the new model. CONCLUSION: Prediction of nitrogen uptake for the substantial nitrate pool of lettuce depends on the water content. Hence, the modified model may assist in making better fertilization decisions and better estimates of nitrogen leaching.     

Autoimmunity as an immune defense against degenerative processes: a primary mathematical model illustrating the bright side of autoimmunity

Self-tolerance, or the ability of the immune system to refrain from destroying the organism's own tissues, is a prerequisite for proper immune system operation. How such self-tolerance is achieved is still a subject of debate. The belief that autoimmunity poses a continuous threat to the organism was challenged by data demonstrating that autoimmunity has a protective function after traumatic injury to the central nervous system. This finding led us to suggest the 'comprehensive immunity' approach by which autoimmunity is viewed as a special case of immunity, namely as a defense mechanism that operates by fighting against the threat of potential destructive activity originated or mediated within the organism, similarly to the immune defense that operates against the threat from exogenous pathogens. We present a primary mathematical spatio-temporal model that supports this concept. The numerical solutions of this model illustrate the beneficial operation of a well-controlled immune response specific to self-antigens residing in the site of lesion. The model also explains how the response to self might be tolerated on a day-to-day basis. In addition, we demonstrate that the same autoimmune response, operating at different levels of regulation, can lead to either an autoimmune disease or a degenerative disorder. This preliminary qualitative model supports our contention that the way autoimmunity is perceived should be revised.