Regulation of insulin-like growth factors I and II and their binding proteins in human bone marrow stromal cells by dexamethasone

Glucocorticoids inhibit the proliferation, but induce the differentiation, of bone marrow stromal cells into osteoblast-like cells. The mechanisms, however, are still conjectural. Since insulin-like growth factors (IGFs) have profound effects on osteoblast growth and differentiation, it is possible that glucocorticoids exert their effects on bone marrow stromal cells in part via regulation of IGFs. Therefore, we analyzed the effects of dexamethasone (Dex) on the expression of IGF I and IGF II in cultured preosteoblastic normal human bone marrow stromal cells (HBMSC). Whereas Dex decreased the concentration of IGF I in the conditioned medium since early in the treatment, the concentration of IGF II was increased progressively as culture period lengthened. As the activities of IGF I and IGF II are regulated by the IGF binding proteins (IGFBPs), we analyzed the effects of Dex on the expression of IGFBPs. Dex increased IGFBP-2 in a time-dependent manner. The increase in IGFBP-2, however, was only to the same extent as that of IGF II at most, depending on the length of treatment. Therefore, the increase in IGFBP-2 would dampen, but not eliminate, the increased IGF II activities. By contrast, Dex decreased IGFBP-3 levels, the latter increasing the bioavailability of IGF II. Although IGFBP-4 mRNA levels were stimulated by Dex, IGFBP-4 concentration in the conditioned medium was unchanged as measured by RIA. IGFBP-5 and IGFBP-6 mRNA levels were decreased by Dex in a time-dependent fashion. IGFBP-5 protein level was also decreased 1–4 days after Dex treatment. IGFBP-1 mRNA was not detectable in HBMSC. These accumulated data indicate that Dex regulates IGF I and IGF II and their binding proteins differentially in normal human bone marrow stromal cells. The progressive increase in IGF II may contribute to Dex-induced cell differentiation. J. Cell. Biochem. 71:449–458, 1998. © 1998 Wiley-Liss, Inc.     

Cardiac allografts in mice congenic at non-H-2 histocompatibility loci

Neonatal mouse heart fragments were grafted under the ear skin of adult recipients. Cardiac allograft survival was evaluated by visual observation of pulsation, electrocardiography, and histology. Employing a series of congenic resistant strains differing from C57BL/10Sn at theH-1, H-3,H-4, H-7, H-8, H-9, H-10, H-11, andH-12 loci, the median survival times of the heart grafts to and from C57BL/10Sn were obtained. The various interallelic combinations resulted in a wide variation of graft survival. Reciprocal transplants frequently showed different survival times.H-1 ^c grafts were rejected by B10.129(5M)/nSn female mice with a median survival time of 90 days.H-1 ^b grafts were not rejected by C57BL/10Sn mice for the experiment's duration of 200 days. The weaker the histocompatibility barrier, the more variable the survival times and the smaller the ratio of rejected to total grafted heart fragments. Female recipients were observed to reject their grafts more rapidly and to reject a higher proportion than males of the same strain. Although the strength of the different non-H-2 barriers generally paralleled that determined by skin transplants, the rankings of the strongest minor barriers were not the same for both tissues.     

Double blind comparative study of omeprazole 10 mg and 30 mg daily for healing duodenal ulcers.

Healing of duodenal ulcers was assessed in 66 patients who received omeprazole either 10 mg or 30 mg daily for four weeks in a double blind study. Healing was rapid in both groups. At two weeks the ulcers in 15 of the 30 patients taking 10 mg daily had healed compared with 28 of the 36 (78%) taking 30 mg daily (p less than 0.03). At four weeks the respective proportions had risen to 83% (25/30) and 94% (33/35) (p greater than 0.05). In non-smokers the proportion of ulcers healed did not differ significantly with the two doses, although there was a trend for less healing at two weeks with 10 mg daily; in smokers significantly fewer ulcers (p less than 0.05) were healed with 10 mg than 30 mg daily at two weeks (7/16 (44%) v 17/21 (81%] and at four weeks (12/16 (75%) v all 21 (100%]. Adverse reactions were few and transient and were considered unlikely to be due to omeprazole.     

Animal movement in the absence of predation: environmental drivers of movement strategies in a partial migration system

Animal movement strategies including migration, dispersal, nomadism, and residency are shaped by broad‐scale spatial‐temporal structuring of the environment, including factors such as the degrees of spatial variation, seasonality and inter‐annual predictability. Animal movement strategies, in turn, interact with the characteristics of individuals and the local distribution of resources to determine local patterns of resource selection with complex and poorly understood implications for animal fitness. Here we present a multi‐scale investigation of animal movement strategies and resource selection. We consider the degree to which spatial variation, seasonality, and inter‐annual predictability in resources drive migration patterns among different taxa and how movement strategies in turn shape local resource selection patterns. We focus on adult Galapagos giant tortoises Chelonoidis spp. as a model system since they display many movement strategies and evolved in the absence of predators of adults. Specifically, our analysis is based on 63 individuals among four taxa tracked on three islands over six years and almost 10⁶ tortoise re‐locations. Tortoises displayed a continuum of movement strategies from migration to sedentarism that were linked to the spatio‐temporal scale and predictability of resource distributions. Movement strategies shaped patterns of resource selection. Specifically, migratory individuals displayed stronger selection toward areas where resources were more predictable among years than did non‐migratory individuals, which indicates a selective advantage for migrants in seasonally structured, more predictable environments. Our analytical framework combines large‐scale predictions for movement strategies, based on environmental structuring, with finer‐scale analysis of space‐use. Integrating different organizational levels of analysis provides a deeper understanding of the eco‐evolutionary dynamics at play in the emergence and maintenance of migration and the critical role of resource predictability. Our results highlight that assessing the potential benefits of differential behavioral responses first requires an understanding of the interactions among movement strategies, resource selection and individual characteristics.     

Are fragments islands? Landscape context and density-area relationships in boreal forest birds

We investigated the role of matrix type as a determinant of change in bird densities with forest patch area (patch area effect) in two different Fennoscandian landscape types: mature forest fragments surrounded by cut-over or regenerating forest and true forested islands surrounded by water. Since the matrix of forested archipelagoes offers no resources to and impedes movement of forest birds, we predict that patch area effects on bird densities should be stronger on forested islands than in forest patches fragmented by forestry. We compiled correlation estimates of the bird density-patch area relationship from the literature and analyzed the data using meta-analysis. Combined correlation coefficients were significantly positive on islands but were not significantly different from 0 in fragments. Within-species comparisons also showed that correlations were consistently more positive on islands than in fragments. On islands but not in fragments, the densities of forest specialist species were more sensitive to area than were the densities of forest generalists, suggesting that specialists are more sensitive to changes in matrix quality. Migration status was only weakly associated with bird responses to island or fragment area. Thus, forest fragments do not function as true islands. We interpret this as the result of compensatory effects of the surrounding matrix in terms of availability of resources and enhanced connectivity (matrix quality hypothesis). A purely patch-centered approach seems an unrealistic framework to analyze population processes occurring in complex landscapes. The characteristics of the habitat matrix should therefore be explicitly incorporated into the assessment of species' responses to habitat fragmentation.     

Diploid/polyploid syntenic shuttle mapping and haplotype-specific chromosome walking toward a rust resistance gene (Bru1) in highly polyploid sugarcane (2n approximately 12x approximately 115)

The genome of modern sugarcane cultivars is highly polyploid ( approximately 12x), aneuploid, of interspecific origin, and contains 10 Gb of DNA. Its size and complexity represent a major challenge for the isolation of agronomically important genes. Here we report on the first attempt to isolate a gene from sugarcane by map-based cloning, targeting a durable major rust resistance gene (Bru1). We describe the genomic strategies that we have developed to overcome constraints associated with high polyploidy in the successive steps of map-based cloning approaches, including diploid/polyploid syntenic shuttle mapping with two model diploid species (sorghum and rice) and haplotype-specific chromosome walking. Their applications allowed us (i) to develop a high-resolution map including markers at 0.28 and 0.14 cM on both sides and 13 markers cosegregating with Bru1 and (ii) to develop a physical map of the target haplotype that still includes two gaps at this stage due to the discovery of an insertion specific to this haplotype. These approaches will pave the way for the development of future map-based cloning approaches for sugarcane and other complex polyploid species.     

Intergenerational and Genealogical Approaches for the Study of Longevity in the Saguenay-Lac-St-Jean Population

The mechanisms of longevity have been the subject of investigations for a number of years. Although the role of genetic factors is generally acknowledged, important questions persist regarding the relative impact of environmental exposures, lifestyle characteristics, and genes. The BALSAC population register offers a unique opportunity to study longevity from an intergenerational and genealogical point of view. Individuals from the Saguenay-Lac-St-Jean population who died at age 90 or older between 1950 and 1974 were selected from this database (n?=?576), along with a control group of individuals born in the same period who died between 50 and 75 years of age. For these subjects and controls, spouses’ ages at death and parental ages at death and at their birth were investigated using regression analysis. Genealogical reconstructions were carried out for each individual, and various analyses were performed on both groups. Both fathers’ and mothers’ mean ages at death were significantly higher among the longer-lived cases than among controls whereas spouses’ ages at death and parental ages at birth had no effect. Regression analysis confirmed the positive effect of both fathers’ and mothers’ age at death. Mean kinship coefficients for the parents’ generations displayed significant differences, indicating that kinship was higher among subjects than controls (this effect was stronger among the oldest 10% of the subjects). Frequencies and genetic contributions of ancestors were very similar for the two groups, and none of these ancestors appeared more likely to have introduced genetic variants involved in longevity patterns in this French Canadian population.