An antimicrobial peptide produced by Bacillus subtilis 168 was isolated and characterized. It was named sublancin 168, and its behavior during Edman sequence analysis and its NMR spectrum suggested that sublancin is a dehydroalanine-containing lantibiotic. A hybridization probe based on the peptide sequence was used to clone the presublancin gene, which encoded a 56-residue polypeptide consisting of a 19-residue leader segment and a 37-residue mature segment. The mature segment contained one serine, one threonine, and five cysteine residues. Alkylation of mature sublancin showed no free sulfhydryl groups, suggesting that one sulfydryl had formed a ␤-methyllanthionine bridge with a dehydrobutyrine derived by posttranslational modification of threonine; with the other four cysteines forming two disulfide bridges. It is unprecedented for a lantibiotic to contain a disulfide bridge. The sublancin leader was similar to known type AII lantibiotics, containing a double-glycine motif that is typically recognized by dual-function transporters. A protein encoded immediately downstream from the sublancin gene possessed features of a dual-function ABC transporter with a proteolytic domain and an ATP-binding domain. The antimicrobial activity spectrum of sublancin was like other lantibiotics, inhibiting Gram-positive bacteria but not Gram-negative bacteria; and like the lantibiotics nisin and subtilin in its ability to inhibit both bacterial spore outgrowth and vegetative growth. Sublancin is an extraordinarily stable lantibiotic, showing no degradation or inactivation after being stored in aqueous solution at room temperature for 2 years. The fact that sublancin is a natural product of B. subtilis 168, for which a great deal of genetic information is available, including the entire sequence of its genome, suggests that sublancin will be an especially good model for studying the potential of lantibiotics as sources of novel biomaterials.

These findings demonstrate that loss or decreased expression of CD10 is an early and frequent event in human prostate cancer and implicates CD10 as a potential therapeutic target for early stage hormone sensitive prostate cancer.

No abstract

CL1-GFP represents an aggressive androgen-independent CaP tumor model derived through androgen deprivation whose pathologic development and molecular properties in animals resembles the clinical characteristics of hormone refractory prostate cancer (HRPC). Metastatic sites of CL1-GFP can be visualized with fluorescence microscopy offering a unique therapeutic model for the evaluation of drug sensitivity and other therapeutic modalities.

CL1-GFP represents an aggressive androgen-independent CaP tumor model derived through androgen deprivation whose pathologic development and molecular properties in animals resembles the clinical characteristics of hormone refractory prostate cancer (HRPC). Metastatic sites of CL1-GFP can be visualized with fluorescence microscopy offering a unique therapeutic model for the evaluation of drug sensitivity and other therapeutic modalities.

We have described a novel fluorescent-labeled clonal hormone refractory prostate cancer tumor system that exhibited marked heterogeneity in its response to various therapeutic modalities, gene expression, and in vivo biology. Our data suggests that given the marked clonal heterogeneity, multi-modality approaches directed against multiple molecular targets rather than single agent therapy will be necessary to adequately eradicate the entire malignant cell population. Clonal tumor lines may allow more accurate examination of molecular pathways involved in tumor progression and resistance to treatment.

Invasion of hepatocytes by Plasmodium sporozoites deposited by Anopheles mosquitoes, and their subsequent transformation into infective merozoites is an obligatory step in the initiation of malaria. Interactions between the sporozoites and hepatocytes lead to a distinct, complex and coordinated cellular and systemic host response. Little is known about host liver cell response to sporozoite invasion, or whether it is primarily adaptive for the parasite, for the host, or for both. Our present study used gene expression profiling of human HepG2-A16 liver cells infected with Plasmodium falciparum sporozoites to understand the host early cellular events and factors influencing parasite infectivity and sporozoite development. Our results show that as early as 30 min following wild-type, non-irradiated sporozoite exposure, the expressions of at least 742 genes was selectively altered. These genes regulate diverse biological functions, such as immune processes, cell adhesion and communications, metabolism pathways, cell cycle regulation, and signal transduction. These functions reflect cellular events consistent with initial host cell defense responses, as well as alterations in host cells to sustain sporozoites growth and survival. Irradiated sporozoites gave very similar gene expression pattern changes, but direct comparative analysis between liver gene expression profiles caused by irradiated and non-irradiated sporozoites identified 29 genes, including glypican-3, that were specifically up-regulated only in irradiated sporozoites. Elucidating the role of this subset of genes may help identify the molecular basis for the irradiated sporozoites inability to develop intrahepatically, and their usefulness as an immunogen for developing protective immunity against pre-erythrocytic stage malaria.

Proteomic analysis by SELDI-TOF-MS technology combined with bioinformatics tools demonstrated differential expression during a 48 h time course suggests a potential role of some of these proteins as biomarkers for the very early stages of AMI, as well as for monitoring early cardiac ischemic recovery.