Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model

Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006). Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007). As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001). This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027) and asparaginase (P = 0.036). We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids.     

Effect of emulsified feeding of oily substrate via submerged ceramic membranes on surfactant production in <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> fermentation

Aqueous two-phase systems often face mass transfer limitations due to very poor miscibility of the fluids, and to enhance the homogeneity (or emulsification) in the reaction volume, high energy inputs are required which result in high shear forces in the culture medium. For the purposes of emulsification, microporous systems have advantages over other conventional methods due to mild operating conditions and narrow droplet-size distribution. In this study, emulsification within the culture volume was achieved by feeding the oily substrate (dispersed phase) into the aqueous medium (dispersion phase) via ceramic membranes integrated in the bioreactor. The method was investigated for bioprocesses aimed at producing rhamnolipids and polyhydroxyalkanoates (PHA). Better homogenization of the mixed volume and hence improved consumption of oily substrate was successful. Surfactants are produced by various bacterial cultures, especially Pseudomonas aeruginosa species, when oil is present as the only carbon source. Are surfactants produced only as a result of bacteria feeding on the oily substrate, or as a requirement to feed on the oily substrate, owing to their surface-active characteristics? This paper also intends to draw some conclusions in this respect.     

The complete mitochondrial DNA sequence of the greater Indian rhinoceros, Rhinoceros unicornis, and the Phylogenetic relationship among Carnivora, Perissodactyla, and Artiodactyla (+ Cetacea)

The sequence (16,829 nt) of the complete mitochondrial genome of the greater Indian rhinoceros, Rhinoceros unicornis, was determined. Like other perissodactyls studied (horse and donkey) the rhinoceros demonstrates length variation (heteroplasmy) associated with different numbers of repetitive motifs in the control region. The 16,829-nt variety of the molecule includes 36 identical control region motifs. The evolution of individual peptide-coding genes was examined by comparison with a distantly related perissodactyl, the horse, and the relationships among the orders Carnivora, Perissodactyla, and Artiodactyla (+ Cetacea) were examined on the basis of concatenated sequences of 12 mitochondrial peptide-coding genes. The phylogenetic analyses grouped Carnivora, Perissodactyla, and Artiodactyla (+ Cetacea) into a superordinal clade and within this clade a sister group relationship was recognized between Carnivora and Perissodactyla to the exclusion of Artiodactyla (+ Cetacea) . On the basis of the molecular difference between the rhinoceros and the horse and by applying as a reference to Artiodactyl/Cetacean divergence set at 60 million years ago (MYA), the evolutionary divergence between the families Rhinocerotidae and Equidae was dated to approximately 50 MYA.      

The mitochondrial genome of the pufferfish,Fugu rubripes,and ordinal teleostean relationships

The small nuclear genome of the pufferfish, Fugu rubripes (order Tetraodontiformes), makes this species highly interesting for genome research. In order to establish the phylogenetic position of the Tetraodontiformes relative to other teleostean orders that might also have a reduced nuclear genome size, we have sequenced the mitochondrial (mt) genome of the pufferfish. The gene order, nucleotide composition and evolutionary rate of the mt genome of the fugu correspond to those of other teleosts. This suggests that the evolution of this genome has not been affected by the processes that led to the dramatic reduction of the size of the nuclear genome of the fugu. The phylogenetic analyses, which were based on the concatenated amino acid sequences of twelve protein-coding mt genes, placed the fugu among the percomorphs. The affinities between the Tetraodontiformes and either the Perciformes or the Zeiformes were limited, however. The common notion of a separate euteleostean clade remained unsupported. The analyses did not support the traditional systematic understanding that the Clupeiformes constitute a basal teleostean lineage. In addition the findings strongly suggest that three teleostean orders, the Perciformes, Zeiformes and Scorpaeniformes, are paraphyletic.     

The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.     

Resolution among major placental mammal interordinal relationships with genome data imply that speciation influenced their earliest radiations

Background  

A number of the deeper divergences in the placental mammal tree are still inconclusively resolved despite extensive phylogenomic analyses. A recent analysis of 200 kbp of protein coding sequences yielded only limited support for the relationships among Laurasiatheria (cow, dog, bat and shrew), probably because the divergences occurred only within a few million years from each other. It is generally expected that increasing the amount of data and improving the taxon sampling enhance the resolution of narrow divergences. Therefore these and other difficult splits were examined by phylogenomic analysis of the hitherto largest sequence alignment. The increasingly complete genome data of placental mammals also allowed developing a novel and stringent data search method.     

The macrofauna and macroflora associated withLaminaria digitata andL. hyperborea at the island of Helgoland (German Bight,North Sea)

This paper describes the macroflora and macrofauna associated with two bull kelp species,Laminaria hyperborea andL. digitata, at the island of Helgoland, North Sea. During a study period of seven months (March–September 1987), 29 macroflora species and 125 macrofauna species were found. The dominant taxonomic groups were Polychaeta (25 species), Bryozoa (17), Amphipoda (14), Hydrozoa (10) and Ascidiae (8). The species maximum was in July. In general,L. hyperborea was preferred as a substrate for settlement toL. digitata. Composition of the communities associated with kelp changed during the season according to exposure to wave action, and according to location on the kelp thallus. The rhizoid community of both kelps bore more species at exposed locations. Wave-exposedL. digitata lacked obvious faunal settlement on both phylloid and cauloid. Phylloid and cauloid ofL. hyperborea were chosen as an attractive substrate at both sheltered and wave-exposed locations, showing an association of encrusting bryozoan and hydrozoan colonies.     

Resistin Gene Expression in Human Adipocytes Is Not Related to Insulin Resistance

Objectives: Obesity is an important risk factor for the development of insulin resistance and type 2 diabetes. Recently, a newly described circulating hormone resistin, which is expressed primarily in adipocytes, has been shown to antagonize insulin action in mice. Resistin, therefore, has been suggested to play a role in the pathogenesis of insulin resistance. Research Methods and Procedures: We studied the expression of the resistin gene in primary cultured human adipocytes and preadipocytes. We also examined resistin gene expression in subcutaneous abdominal adipocytes in women (n = 24) over a wide range of body weight and insulin sensitivity. Results: Whereas resistin gene expression was barely detectable in mature adipocytes, it was highly expressed in preadipocytes. Adipogenic differentiation of preadipocytes was associated with a time-dependent down-regulation of resistin gene expression. There was no relationship between body weight, insulin sensitivity, or other metabolic parameters and adipocyte resistin gene expression in the clinical study. Discussion: Together these findings do not support an important role of adipose-tissue resistin gene expression in human insulin resistance.     

Mitogenomic Analyses Place the Gharial (Gavialis gangeticus) on the Crocodile Tree and Provide Pre-K/T Divergence Times for Most Crocodilians

Based on morphological analyses, extant members of the order Crocodylia are divided into three families, Alligatoridae, Crocodylidae, and Gavialidae. Gavialidae includes one species, the gharial, Gavialis gangeticus. In this study we have examined crocodilian relationships in phylogenetic analyses of seven mitochondrial genomes that have been sequenced in their entirety. The analyses did not support the morphologically acknowledged separate position of the gharial in the crocodilian tree. Instead the gharial joined the false gharial (Tomistoma schlegelii) on a common branch that was shown to constitute a sister group to traditional Crocodylidae (less Tomistoma). Thus, the analyses suggest the recognition of only two Crocodylia families, Alligatoridae and Crocodylidae, with the latter encompassing traditional Crocodylidae plus Gavialis/Tomistoma. A molecular dating of the divergence between Alligatoridae and Crocodylidae suggests that this basal split among recent crocodilians took place ≈140 million years before present, at the Jurassic/Cretaceous boundary. The results suggest that at least five crocodilian lineages survived the mass extinction at the KT boundary. [Reviewing Editor: Dr. Nicolas Galtier]