Metabolism of Diethyl Ether and Cometabolism of Methyl tert-Butyl Ether by a Filamentous Fungus, a Graphium sp

In this study, evidence for two novel metabolic processes catalyzed by a filamentous fungus, Graphium sp. strain ATCC 58400, is presented. First, our results indicate that this Graphium sp. can utilize the widely used solvent diethyl ether (DEE) as the sole source of carbon and energy for growth. The kinetics of biomass accumulation and DEE consumption closely followed each other, and the molar growth yield on DEE was indistinguishable from that with n-butane. n-Butane-grown mycelia also immediately oxidized DEE without the extracellular accumulation of organic oxidation products. This suggests a common pathway for the oxidation of both compounds. Acetylene, ethylene, and other unsaturated gaseous hydrocarbons completely inhibited the growth of this Graphium sp. on DEE and DEE oxidation by n-butane-grown mycelia. Second, our results indicate that gaseous n-alkane-grown Graphium mycelia can cometabolically degrade the gasoline oxygenate methyl tert-butyl ether (MTBE). The degradation of MTBE was also completely inhibited by acetylene, ethylene, and other unsaturated hydrocarbons and was strongly influenced by n-butane. Two products of MTBE degradation, tert-butyl formate (TBF) and tert-butyl alcohol (TBA), were detected. The kinetics of product formation suggest that TBF production temporally precedes TBA accumulation and that TBF is hydrolyzed both biotically and abiotically to yield TBA. Extracellular accumulation of TBA accounted for only a maximum of 25% of the total MTBE consumed. Our results suggest that both DEE oxidation and MTBE oxidation are initiated by cytochrome P-450-catalyzed reactions which lead to scission of the ether bonds in these compounds. Our findings also suggest a potential role for gaseous n-alkane-oxidizing fungi in the remediation of MTBE contamination.     

Tyrosine kinase-deficient Wv c-kit induces mast cell adhesion and chemotaxis

W/W^v mice are deficient intissue mast cells, and mast cells cultured from these mice do notproliferate in response to the c-kit ligand, stem cell factor (SCF). Inthis paper, we report that mouse bone marrow cultured mast cellsderived from W/W^v mice do adhereto fibronectin in the presence of SCF and exhibit chemotaxis to SCF,and we explore this model for the understanding of c-kit-mediatedsignaling pathways. Both in vitro and in vivo (in intact cells)phosphorylation experiments demonstrated a low residual level ofW/W^v c-kit proteinphosphorylation. SCF-induced responses inW/W^v mast cells were abolished bythe tyrosine kinase inhibitor herbimycin A and by thephospatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin butwere not affected by protein kinase C inhibitors. These observationsare consistent with the conclusions thatW^v c-kit initiates a signalingprocess that is PI 3-kinase dependent and that mutatedW^v c-kit retains the ability toinitiate mast cell adhesion and migration.

     

ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression

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Fatal disseminated Cryptococcus gattii infection in New Mexico

We report a case of fatal disseminated infection with Cryptococcus gattii in a patient from New Mexico. The patient had no history of recent travel to known C. gattii-endemic areas. Multilocus sequence typing revealed that the isolate belonged to the major molecular type VGIII. Virulence studies in a mouse pulmonary model of infection demonstrated that the strain was less virulent than other C. gattii strains. This represents the first documented case of C. gattii likely acquired in New Mexico.     

Localization of the beta-like globin gene cluster and the genes for parathyroid hormone and c-Harvey-ras 1 to region q14----q21 of rabbit chromosome 1 by in situ hybridization

The rabbit beta-like globin gene cluster (HBBC), comprised of epsilon-, gamma-, delta-, and beta-globin genes (HBE, HBG, HBD, and HBB, respectively), has been mapped to chromosome 1, region q14----q21, by in situ hybridization using probes for rabbit HBE and HBG. Probes for the human parathyroid hormone gene (PTH) and the Harvey-ras 1 protooncogene (HRAS1) also localize to this region by in situ hybridization. Thus, these genes are syntenic in lagomorphs as well as four other mammalian orders (primates, rodents, carnivores, and artiodactyls). The mapping data in rabbits provide further evidence that this synteny is strongly conserved in the evolution of mammalian chromosomes.     

Characterization of a widely expressed gene (LUC7-LIKE; LUC7L) defining the centromeric boundary of the human alpha-globin domain

We have identified the first gene lying on the centromeric side of the alpha-globin gene cluster on human 16p13.3. The gene, called 16pHQG;16 (HGMW-approved symbol LUC7L), is widely transcribed and lies in the opposite orientation with respect to the alpha-globin genes. This gene may represent a mammalian heterochromatic gene, encoding a putative RNA-binding protein similar to the yeast Luc7p subunit of the U1 snRNP splicing complex that is normally required for 5' splice site selection. To examine the role of the 16pHQG;16 gene in delimiting the extent of the alpha-globin regulatory domain, we mapped its mouse orthologue, which we found to lie on mouse chromosome 17, separated from the mouse alpha-cluster on chromosome 11. Establishing the full extent of the human 16pHQG;16 gene has allowed us to define the centromeric limit of the region of conserved synteny around the human alpha-globin cluster to within an 8-kb segment of chromosome 16.     

Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis

Intracerebral infection of mice with mouse hepatitis virus, a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis that progresses to a chronic demyelinating disease. The ensuing neuropathology during the chronic stage of disease is primarily immune mediated and similar to that of the human demyelinating disease multiple sclerosis. Secretion of chemokines within the CNS signals the infiltration of leukocytes, which results in destruction of white matter and neurological impairment. The CC chemokine ligand (CCL)5 is localized in white matter tracts undergoing demyelination, suggesting that this chemokine participates in the pathogenesis of disease by attracting inflammatory cells into the CNS. In this study, we administer a mAb directed against CCL5 to mice with established mouse hepatitis virus-induced demyelination and impaired motor skills. Anti-CCL5 treatment decreased T cell accumulation within the CNS based, in part, on viral Ag specificity, indicating the ability to differentially target select populations of T cells. In addition, administration of anti-CCL5 improved neurological function and significantly (p < or = 0.005) reduced the severity of demyelination and macrophage accumulation within the CNS. These results demonstrate that the severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination.