Lactational competence and involution of the mouse mammary gland require plasminogen

Urokinase-type plasminogen activator expression is induced in the mouse mammary gland during development and post-lactational involution. We now show that primiparous plasminogen-deficient (Plg(-/-)) mice have seriously compromised mammary gland development and involution. All mammary glands were underdeveloped and one-quarter of the mice failed to lactate. Although the glands from lactating Plg(-/-) mice were initially smaller, they failed to involute after weaning, and in most cases they failed to support a second litter. Alveolar regression was markedly reduced and a fibrotic stroma accumulated in Plg(-/-) mice. Nevertheless, urokinase and matrix metalloproteinases (MMPs) were upregulated normally in involuting glands of Plg(-/-) mice, and fibrin did not accumulate in the glands. Heterozygous Plg(+/-) mice exhibited haploinsufficiency, with a definite, but less severe mammary phenotype. These data demonstrate a critical, dose-dependent requirement for Plg in lactational differentiation and mammary gland remodeling during involution.     

Microarray,SAGE and their applications to cardiovascular diseases

The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE     

Crystal structures of CheY from Thermotoga maritima do not support conventional explanations for the structural basis of enhanced thermostability.

The crystal structure of CheY protein from Thermotoga maritima has been determined in four crystal forms with and without Mg++ bound, at up to 1.9 A resolution. Structural comparisons with CheY from Escherichia coli shows substantial similarity in their folds, with some concerted changes propagating away from the active site that suggest how phosphorylated CheY, a signal transduction protein in bacterial chemotaxis, is recognized by its targets. A highly conserved segment of the protein (the "y-turn loop," residues 55-61), previously suggested to be a rigid recognition determinant, is for the first time seen in two alternative conformations in the different crystal structures. Although CheY from Thermotoga has much higher thermal stability than its mesophilic counterparts, comparison of structural features previously proposed to enhance thermostability such as hydrogen bonds, ion pairs, compactness, and hydrophobic surface burial would not suggest it to be so.     

A comparative study of straight chain and branched chain fatty acid oxidation in skin fibroblasts from patients with peroxisomal disorders.

The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by normal fibroblast homogenates was several-fold greater compared to the oxidation of the two branched chain fatty acids. The effect of phosphatidylcholine, alpha-cyclodextrin, and bovine serum albumin on the three activities suggests that different enzymes are involved in the beta-oxidation of straight chain and branched chain fatty acids. Homogenates of fibroblasts from patients with a deficiency in peroxisomes (Zellweger syndrome and infantile Refsum's disease) showed a normal ability to beta-oxidize stearic acid, but the oxidation of pristanic and tetramethylheptadecanoic acid was decreased. Concomitantly, 14CO2 production from the branched chain fatty acids by Zellweger fibroblasts in culture (but not from stearic acid) was greatly diminished. The Zellweger fibroblasts also showed a marked reduction in the amount of water-soluble metabolites from the radiolabeled branched chain fatty acids that are released into the culture medium. The data presented indicate that the oxidation of alpha- and gamma-methyl isoprenoid-derived fatty acids takes place largely in peroxisomes in human skin fibroblasts.     

Management and diversity of arthropods inCalluna heathland

Heathlands, dominated byCalluna vulgaris, are located along the western seaboard of Europe. Most undergo a cyclical succession as the heather plants pass through four definable growth-phases over a period of about 30 years. Examples of upland heathlands are drawn from the North York Moors National Park, an area of Jurassic rocks in the north of England (approximately 54°25N, 0°55W). Botanical diversity is low. In a survey of 10 heathlands selected to encompass the botanical variation of the heathlands of the National Park, only 40 species of higher plants and 31 species of mosses were recorded (2.2% and 4.5% of the British flora, respectively).However, diversity of some invertebrate groups is high. Totals of 54 species of carabid beetles and 127 species of spiders were recorded (15.3% and 20.4% of the British fauna, respectively). At least two environmental gradients appear to influence the species composition of the invertebrate assemblages: a wet-dry gradient and the height of the vegetation (corresponding to the growth-phase of the heather). Experimental areas on three heathlands were burnt and cut, the traditional and more modern methods of heather management. Analysis of both the spider and beetle data indicated that the species assemblages were primarily influenced by the growth-phase of the heather. Some of the nationally rarer species are associated with the open conditions of recently-cut or burnt heathland. An altitudinal effect was also inferred since heathland at 410 m above sea level tended to be less species-rich than heathlands at ca 260 m above sea level.These results present a paradox. Although botanical diversity is extremely low, and although it is a non-natural ecosystem maintained by fire and grazing management to prevent a succession to woodland, arthropod diversity can be extremely high. The discussion focuses on the importance of upland heathlands in the conservation of insect and spider diversity, as well as on the value of these upland areas for conservation more generally.C. vulgaris is seen to be a key species on which many other species depend. One conclusion is that there is insufficient effort, nationally and especially internationally, to conserve the heathlands of Europe.     

Determination of the rate-limiting step(s) in the biosynthetic pathways leading to penicillin and cephalosporin

Summary This paper is a review of strategies that have been used, or that could be used, to determine the rate-limiting step(s) in the biosynthetic pathways leading to penicillin or cephalosporin. Information is summarized from published material that involves studies with low-producing strains ofPenicillium chrysogenum andCephalosporium acremonium. We also summarize information derived from some high-producing production strains. Identification of the rate-limiting step(s) was of great interest to us as the first step in a rational program to further improve antibiotic titers of these highly developed strains. A number of approaches that could be used to elucidate the rate-limiting step(s) are described herein.     

RE-EVALUATION OF CERTAIN KEY RELATIONSHIPS IN THE ALISMATIDAE: FLORAL ORGANOGENESIS OF SCHEUCHZERIA PALUSTRIS (SCHEUCHZERIACEAE)

Transition to flowering in the North-temperate bog plant Scheuchzeria palustris occurs in early May and results in the formation of a simple raceme with six flowers. Five of the flowers are subtended by large foliar bracts, while the sixth and last-formed flower on the inflorescence remains ebracteate. The individual flowers develop along a clearly trimerous pattern. The three outer tepals develop first, arising almost simultaneously at the periphery of the triangular floral apex. They are followed closely by the development of the three anti-tepalous outer stamens. The three inner tepals are next in the developmental sequence, alternating with the outer whorl of tepal-stamen pairs but arising at a slightly higher level on the floral meristem. Three inner stamens are initiated opposite the inner tepal primordia. Finally, three gynoecial primordia are initiated on the remaining central portion of the floral apex and alternating with the inner whorl of tepal-stamen pairs. Each carpel develops at first as a horseshoe-shaped structure. Two ovules form in each carpel, initiating on the adaxial margin of the carpel wall. Histogenesis of all floral appendages involves initially periclinal divisions in the second tunica layer followed by corresponding anticlinal divisions in the first tunica layer and concurrent activity in the underlying corpus. Separate procambial strands differentiate acropetally from the inflorescence axis to each tepal-stamen pair and then bifurcate. The vascular connection to the gynoecium develops directly from the strands in the tepal-stamen pairs. The results of this developmental study of the flower of S. palustris have a significant bearing on the positioning of this and related taxa within the Alismatidae and on the speculation of the phylogeny of the monocotyledon flower.     

Studies on populations of Folsomia candida (Insecta: Collembola)

Summary Experiments are described that were designed to investigate the effects of food availability and rate of exploitation on the growth and production of populations of Folsomia candida (Willem). In an initial experiment in which there was excess food it was found that increasing the rate of exploitation resulted in increases in both the numerical and biomass productivity of the populations. In a second experiment it was shown that, when there is severe competition for food, the rate of exploitation does not affect either the biomass or the numerical production. It is concluded that the effect of overcrowding, in the form of competition for space, does contribute to the growth in numbers of populations, but that the supply of food plays a more important role in regulating the population. Anomalous results, showing that exploitation has a lesser effect when there is severe competition for food, are discussed.     

Lowland woodland structure and pattern and the distribution of arboreal,phytophagous arthropods

We investigated factors that limited the distribution of phytophagous species within a woodiand system in Midlothian, Scotland. A pattern analysis was conducted of phytophagous species on a total of 45 Fagus sylvatica within 15 woodlands. Species richness counted on collected leaves was tested against within-and between-wood variables. Variables used in a regression with arthropod data from Fagus were used to estimate the phytophage richness on Betula pendula and Quercus robur in the same woods. Convariance in the number of phytophages in sampled woods was found for Fagus over three years and for Fagus, Betula and Quercus in 1992. Association analysis was used to classify the woods into species rich or poor based on presence or absence matrices. The main factors that limit phytophages on Fagus (gaps along the woodland edge, depth and species richness of the field layer. density of leaf litter and the extent of contiguous woodland cover, when including hedgerows and lines of trees) affect phytophages of similar life history strategy on other tree species within the same woods. Eighty-six per cent of species were lost because certain life history stages were vulnerable to factors that prevail in woods of poor structure. The nature conservation value of woodlands could be assessed using the correlated vulnerability of particular phytophages across tree species under specific woodland conditions.