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In search of new antileukopenia agents, twenty dithiolopyrrolone derivatives were synthesized and evaluated for their leukocyte-increasing activities in normal mice. Among the synthesized compounds 4-23, compounds 5 and 6 showed significant leukocyte-increasing activity ( p < 0.01), and compounds 4, 9 and 16 had a moderate effect ( p < 0.05). Compound 5 also displayed stronger leukocyte-increasing activity than that of the positive recombinant human granulocyte colony stimulating factor (rhG-CSF). Above all, compound 5 would be a potential antileukopenia agent which deserved further research. [ABSTRACT FROM AUTHOR]

Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases. aspartyl proteases, and acid sphingomyelinases) was found in the M. g!obosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex. [ABSTRACT FROM AUTHOR]

We will show that ocean-reflected signals from the global positioning system (GPS) navigation satellite constellation can be detected from a low-earth orbiting satellite and that these signals show rough correlation with independent measurements of the sea winds. We will present waveforms of ocean-reflected GPS signals that have been detected using the experiment onboard the United Kingdom's Disaster Monitoring Constellation satellite and describe the processing methods used to obtain their delay and Doppler power distributions. The GPS bistatic radar experiment has made several raw data collections, and reflected GPS signals have been found on all attempts. The down linked data from an experiment has undergone extensive processing, and ocean-scattered signals have been mapped across a wide range of delay and Doppler space revealing characteristics which are known to be related to geophysical parameters such as surface roughness and wind speed. Here we will discuss the effects of integration time, reflection incidence angle and examine several delay-Doppler signal maps. The signals detected have been found to be in general agreement with an existing model (based on geometric optics) and with limited independent measurements of sea winds; a brief comparison is presented here. These results demonstrate that the concept of using bistatically reflected global navigation satellite systems signals from low earth orbit is a viable means of ocean remote sensing. [ABSTRACT FROM AUTHOR]

The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Glyceraldehyde-3-phosphate dehydrogenase is a pivotal glycolytic enzyme and implicated in many human cancers. Results: GAPDH acetylation promotes its activity in response to glucose via the action of PCAF and HDAC5. Conclusion: GAPDH acetylation promotes cell proliferation and tumor growth. Significance: This study demonstrates a critical role of GAPDH acetylation in tumor growth and provides potential therapy target for cancer. [ABSTRACT FROM AUTHOR]

Dandruff and seborrheic dermatitis (D/SD) are common hyperproliferative scalp disorders with a similar etiology. Both result, in part, from metabolic activity of Malassezia globosa and Malassezia restricta, commensal basidiomycete yeasts commonly found on human scalps. Current hypotheses about the mechanism of D/SD include Malassezia-induced fatty acid metabolism, particularly lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids. We report that lipase activity was detected in four species of Malassezia, including M. globosa. We isolated lipase activity by washing M. globosa cells. The isolated lipase was active against diolein, but not triolein. In contrast, intact cells showed lipase activity against both substrates, suggesting the presence of at least another lipase. The diglyceride-hydrolyzing lipase was purified from the extract, and much of its sequence was determined by peptide sequencing. The corresponding lipase gene (LIP1) was cloned and sequenced. Confirmation that LIP1 encoded a functional lipase was obtained using a covalent lipase inhibitor. LIP1 was differentially expressed in vitro. Expression was detected on three out of five human scalps, as indicated by reverse transcription-PCR. This is the first step in a molecular description of lipid metabolism on the scalp, ultimately leading toward a test of its role in D/SD etiology.Journal of Investigative Dermatology (2007) 127, 2138–2146; doi:10.1038/sj.jid.5700844; published online 26 April 2007 [ABSTRACT FROM AUTHOR]