Synthetic segments of the mammalian beta AR are preferentially recognized by cAMP-dependent protein kinase and protein kinase C

Desensitization of the beta-adrenergic receptor has been correlated in some cell systems with receptor phosphorylation. Various kinases have been implicated in these phosphorylation processes, including both cAMP-dependent protein kinase and protein kinase C. In the present study, we have utilized the protein sequence information obtained from the cloning of the mammalian beta-adrenergic receptor to prepare synthetic peptides corresponding to regions of the receptor which would be predicted to act as possible substrates for these kinases in vivo. Two of these receptor-derived peptides were found to serve as substrates for these protein kinases. A peptide corresponding to amino acids 257-264 of the beta-receptor is the preferred substrate for the cAMP-dependent protein kinase, while protein kinase C showed a marked preference for phosphorylation of a peptide corresponding to residues 341-351 of the beta-adrenergic receptor.     

Dry mass changes in germinating spores of Diplodia maydis

Summary The dry mass of two-celled Diplodia maydis spores was measured both before and after germination by quantitative interference microscopy. The dry mass of spores declined approximately 50% during germination. However, the dry mass of germinating spores plus the dry mass of their germ tubes was greater than the dry mass of spores before germination. We conclude that the germinating spores absorbed nutrients released from non-germinating spores.The dry mass of fungal spores can be estimated by weighing large numbers of spores and determining the mean from sample spore counts. Mumford and Pappelis(4) determined the total dry mass of individual spores of Fusarium roseum and the contained lipid bodies before and after spores germinated using quantitative interference microscopy. The mean spore dry mass before germination was 57 pg. Lipid bodies accounted for about 61% of that mass and decreased as spores germinated. The total dry mass of the spore and germ tube 24 hr later greatly exceeded that of the spore before germination. Quantitative interference microscopy has been used to measure the dry mass of various types of cells. Kulfinski and Pappelis (3) recently reviewed how this technique has been applied to plant cells. Technical aspects of interference microscopy have been described by Ross (6).The purpose of this study was to examine the dry mass changes in Diplodia maydis (Berk.) Sacc. with and without germ tubes through the use of interference microscopy.     

Mutation spectra of smoky coal combustion emissions in Salmonella reflect the TP53 and KRAS mutations in lung tumors from smoky coal-exposed individuals

Nonsmoking women in Xuan Wei County, Yunnan Province, China who use smoky coal for cooking and heating in poorly ventilated homes have the highest lung cancer mortality rate in China, and their lung cancer is linked epidemiologically to their use of smoky coal. The emissions contain 81% organic matter, of which 43% is polycyclic aromatic hydrocarbons (PAHs). Exposure assessment and molecular analysis of the lung tumors from nonsmoking women who use smoky coal strongly indicate that PAHs in the emissions are a primary cause of the elevated lung cancer in this population. Here we have determined the mutation spectra of an extract of smoky coal emissions in Salmonella TA98 and TA100; the extract was not mutagenic in TA104. The extract was 8.7 x more mutagenic in TA100 with S9 than without (8.7 rev/microg versus 1.0 rev/microg) and was >3 x more mutagenic in TA100 than in TA98--consistent with a prominent role for PAHs in the mutagenicity of the extract because PAHs are generally more mutagenic in the base-substitution strain TA100 than in the frameshift strain TA98. The extract induced only a hotspot mutation in TA98; another combustion emission, cigarette smoke condensate (CSC), also induces this single class of mutation. In TA100, the mutation spectra of the extract were not significantly different in the presence or absence of S9 and were primarily (78-86%) GC --> TA transversions. This mutation is induced to a similar extent by CSC (78%) and the PAH benzo[a]pyrene (B[a]P) (77%). The frequency of GC --> TA transversions induced in Salmonella by the extract (78-86%) is similar to the frequency of this mutation in the TP53 (76%) and KRAS (86%) genes of lung tumors from nonsmoking women exposed to smoky coal emissions. The mutation spectra of the extract reflect the presence of PAHs in the mixture and support a role for PAHs in the induction of the mutations and tumors due to exposure to smoky coal emissions.     

中国的炭疽杆菌DNA分型及其地理分布

炭疽广泛分布于中国各地,特别是西部地区,并经常造成人畜疾病,在一项合作研究中,用多位点VNTR分析（MLVA）对从1952-1998年自中国主要地理流行区域分离的病人,病畜和土壤等来源的炭疽杆菌进行了基因分型,MLVA分析结果揭示了21种新的基因型,其等位基因组合在以前世界范围分离物的研究中未曾发现,此外,分离物的分群显示,A3b组是地理上最广泛分布的基因组,说明该组可能是中国的“地方流行株”。而来自古丝绸之路重要贸易中心新疆的大量分离株其基因型特别分散。     

Importance of ambient saturation deficits in an epizootic of the fungus Neozygites floridana in cassava green mites (Mononychellus tanajoa)

The mite-pathogenic fungus Neozygites floridana Fisher (Entomophthorales: Neozygitaceae) is considered to have potential for the biological control of the cassava green mite, Mononychellus tanajoa (Bondar). However, its activity is sporadic and laboratory data suggest a strong dependence on night-time saturation deficits for transmission. We report on an epizootic of this fungus in a mite population in northeastern Brazil. During the epizootic, host populations appeared to be limited by a combination of the pathogen and a predatory mite Neoseiulus idaeus (Acari: Phytoseiidae). When temperatures increased, the epizootic finished and the host population began to grow. Abiotic conditions could not explain the variation in host mortality following pickup of infective propagules in this epizootic. However, night-time saturation did help to explain the variation in transmission from infective cadavers to newly killed hosts. This supports laboratory observations that horizontal transmission between hosts is determined mainly by saturation deficits, while the process of infection is little affected by abiotic conditions. A further field observation was the near-absence of resting spores in dead mites (ca. 0.1% of cadavers), suggesting that the pathogen population was unsuccessful in producing inoculum to infect future M. tanajoa populations. The implications are that this pathogen will only be effective as a biological control agent in periods of high relative humidity, and establishment in new areas may be limited by resting spore formation. This revised version was published online in July 2006 with corrections to the Cover Date.     

MicroRNAs in systemic rheumatic diseases

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs about 21 nucleotides in length. miRNAs have been shown to regulate gene expression and thus influence a wide range of physiological and pathological processes. Moreover, they are detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. The role of miRNAs is evident in various malignant and nonmalignant diseases, and there is accumulating evidence also for an important role of miRNAs in systemic rheumatic diseases. Abnormal expression of miRNAs has been reported in autoimmune diseases, mainly in systemic lupus erythematosus and rheumatoid arthritis. miRNAs can be aberrantly expressed even in the different stages of disease progression, allowing miRNAs to be important biomarkers, to help understand the pathogenesis of the disease, and to monitor disease activity and effects of treatment. Different groups have demonstrated a link between miRNA expression and disease activity, as in the case of renal flares in lupus patients. Moreover, miRNAs are emerging as potential targets for new therapeutic strategies of autoimmune disorders. Taken together, recent data demonstrate that miRNAs can influence mechanisms involved in the pathogenesis, relapse, and specific organ involvement of autoimmune diseases. The ultimate goal is the identification of a miRNA target or targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the development of disease.     

Frequent coexistence of anti-topoisomerase I and anti-U1RNP autoantibodies in African American patients associated with mild skin involvement: a retrospective clinical study

Introduction  

The presence of anti-topoisomerase I (topo I) antibodies is a classic scleroderma (SSc) marker presumably associated with a unique clinical subset. Here the clinical association of anti-topo I was reevaluated in unselected patients seen in a rheumatology clinic setting.     

The High Arctic glacial ecosystem: new insights from nutrient budgets

This paper describes detailed budgets of water, Cl⁻, dissolved Si and both inorganic and organic forms of nitrogen and phosphorus for two small glacier basins in Arctic Svalbard (Midre Lovénbreen and AustreBrøggerbreen). Rates of nutrient deposition are modest, dominated by inorganic nitrogen and episodically enhanced by extreme events. Hence deposition rates are also variable, ranging from 20 to 72 kg NO₃-N km⁻² a⁻¹ and 10–37 kg NH₄-N km⁻² a⁻¹ over just two consecutive years. Deposition of dissolved organic and particulate forms of nitrogen (DONand PN respectively) also appears significant and therefore requires further investigation (3–8 kg DON-N km⁻² and 7–26 kg PN-N km⁻² during winter – no summer data are available). Evidence for microbially mediated nutrient cycling within the glacial system is clear in the nutrient budgets, as is the release of large phosphorus, Si and organic/particulate nitrogen fluxes by subglacial erosion. The latter is entirely dependent upon the presence of subglacial drainage, promoting silicate mineral dissolution and the erosion of largely unweathered apatite. The large DON and PN fluxes are surprising and may relate to young organic nitrogen associated with microbial life within the glaciers. This is because wide spread assimilation of NH₄⁺ and perhaps even nitrification occurs on the glacier surface, most likely within abundant cryoconite holes. Further microbial activity also occurs at the glacier bed, where denitrification and sulphate reduction is now known to take place. Thus a two component ‘glacial ecosystem’ is proposed that is highly sensitive to climate change.     

Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inhibitors of inducible nitric oxide synthase

Syntheses and nitric oxide synthase inhibitory activity of cyclic amidines containing 5,6- 6,6- and 7,6-fused systems are described. X-ray structure determination facilitated the assignment of the stereochemistry of the most active compounds perhydro-2-iminoisoquinoline (8a) and perhydro-2-iminopyrindine (10a). Both 8a and 10a are very potent inhibitors of iNOS, with excellent selectivity over eNOS and they are orally active in rats with long duration suitable for once or twice a day dosing.