SEED SET AND SEED PREDATION IN PEDICULARIS FURBISHIAE,A RARE ENDEMIC OF THE ST. JOHN RIVER,MAINE

We measured seed set and losses due to mammal and insect predation during 1983 in seven northern Maine populations of Furbish's Lousewort (Pedicularis furbishiae S. Wats.; Scrophulariaceae), a perennial herb endemic to the banks of the St. John River. Only about a quarter of initiated flowers developed a capsule with a full complement (mean = 25) of seeds. Secondary (lateral) inflorescences matured a smaller proportion of capsules than primary (terminal) inflorescences. About 58% of the initiated flower primordia were aborted or did not develop mature seeds by early September; this was probably not due to pollinator limitation. Several agents could have reduced seed production. Although spittlebugs infested between 3 and 30% (average 20%) of developing flower scapes by population, they did not depress the number of inflorescences initiated or the number of capsules matured. In contrast, 74% of capsules containing a lepidopteran seed predator (the plume moth Amblyptilia pica [Walsingham], newly discovered as a seed predator on P. furbishiae) had no seeds (mean = 3 seeds). Seed predation affected 39% of the potentially maturable capsules. In 6–30% of all capsules preyed upon, the lepidopteran was parasitized by an ichneumonoid wasp larva; these capsules matured about 7 seeds. Herbivory by rabbits, rodents, and deer also reduced seed set, eliminating 98% of the scapes at one site, and averaging 40% for other populations. Mammals and insects together removed at least 62% of maturable seeds. Populations varied widely in predation and seed set. Predispersal seed loss in P. furbishiae, coupled with slow seedling growth and occasional catastrophic mortality from ice scour and erosion, could limit population growth in this rare endemic.     

Methylobacterium Species Promoting Rice and Barley Growth and Interaction Specificity Revealed with Whole-Cell Matrix-Assisted Laser Desorption / Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) Analysis

Methylobacterium species frequently inhabit plant surfaces and are able to utilize the methanol emitted from plants as carbon and energy sources. As some of the Methylobacterium species are known to promote plant growth, significant attention has been paid to the mechanism of growth promotion and the specificity of plant–microbe interactions. By screening our Methylobacterium isolate collection for the high growth promotion effect in vitro, we selected some candidates for field and pot growth tests for rice and barley, respectively. We found that inoculation resulted in better ripening of rice seeds, and increased the size of barley grains but not the total yield. In addition, using whole-cell matrix-assister laser desorption/ionization- time-of-flight mass spectrometry (MALDI-TOF/MS) analysis, we identified and classified Methylobacterium isolates from Methylobacterium-inoculated rice plants. The inoculated species could not be recovered from the rice plants, and in some cases, the Methylobacterium community structure was affected by the inoculation, but not with predomination of the inoculated species. The isolates from non-inoculated barley of various cultivars grown in the same field fell into just two species. These results suggest that there is a strong selection pressure at the species level of Methylobacterium residing on a given plant species, and that selection of appropriate species that can persist on the plant is important to achieve growth promotion.     

Inactivation of Tp53 and Pten drives rapid development of pleural and peritoneal malignant mesotheliomas

Malignant mesothelioma (MM) is a therapy‐resistant cancer arising primarily from the lining of the pleural and peritoneal cavities. The most frequently altered genes in human MM are cyclin‐dependent kinase inhibitor 2A (CDKN2A), which encodes components of the p53 (p14ARF) and RB (p16INK4A) pathways, BRCA1‐associated protein 1 (BAP1), and neurofibromatosis 2 (NF2). Furthermore, the p53 gene (TP53) itself is mutated in ~15% of MMs. In many MMs, the PI3K–PTEN–AKT–mTOR signaling node is hyperactivated, which contributes to tumor cell survival and therapeutic resistance. Here, we demonstrate that the inactivation of both Tp53 and Pten in the mouse mesothelium is sufficient to rapidly drive aggressive MMs. Pten^L/L;Tp53^L/L mice injected intraperitoneally or intrapleurally with adenovirus‐expressing Cre recombinase developed high rates of peritoneal and pleural MMs (92% of mice with a median latency of 9.4 weeks and 56% of mice with a median latency of 19.3 weeks, respectively). MM cells from these mice showed consistent activation of Akt–mTor signaling, chromosome breakage or aneuploidy, and upregulation of Myc; occasional downregulation of Bap1 was also observed. Collectively, these findings suggest that when Pten and Tp53 are lost in combination in mesothelial cells, DNA damage is not adequately repaired and genomic instability is widespread, whereas the activation of Akt due to Pten loss protects genomically damaged cells from apoptosis, thereby increasing the likelihood of tumor formation. Additionally, the mining of an online dataset (The Cancer Genome Atlas) revealed codeletions of PTEN and TP53 and/or CDKN2A/p14ARF in ~25% of human MMs, indicating that cooperative losses of these genes contribute to the development of a significant proportion of these aggressive neoplasms and suggesting key target pathways for therapeutic intervention.     

Protective role of carnitine in breast cancer via decreasing arginase activity and increasing nitric oxide

Breast cancer remains one of the most common types of cancer. High levels of arginase and ornithine in different carcinomas may indicate their relation to cancer. Carnitine is a cofactor required for the transformation of free long-chain fatty acids into acetyl-carnitines. We have examined the protective effect of carnitine and the possibility that it disturbs arginase-nitric oxide (NO) interaction. Histopathological examination, arginase activity, ornithine and NO levels were determined in tumour tissues. Mitotic cells significantly decreased in the treatment group. Tissue arginase activity and ornithine levels decreased significantly with carnitine. NO levels were significantly higher in the treatment group. One of the possible mechanisms of carnitine's protective role in tumour progression might be its promotion of NO. This mechanism could decrease the production of tumour-promoting agents, polyamines, and increase the production of NO, thereby exerting a protective effect on cancer development.     

Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors

The insulin-like growth factor-1 receptor (IGF-1R) plays an important role in the regulation of cell growth and differentiation, and in protection from apoptosis. IGF-1R has been shown to be an appealing target for the treatment of human cancer. Herein, we report the synthesis, structure-activity relationships (SAR), X-ray cocrystal structure and in vivo tumor study results for a series of 2,4-bis-arylamino-1,3-pyrimidines.     

Immunodominance of CD4 T cells to foreign antigens is peptide intrinsic and independent of molecular context: implications for vaccine design

Immunodominance refers to the restricted peptide specificity of T cells that are detectable after an adaptive immune response. For CD4 T cells, many of the mechanisms used to explain this selectivity suggest that events related to Ag processing play a major role in determining a peptide's ability to recruit CD4 T cells. Implicit in these models is the prediction that the molecular context in which an antigenic peptide is contained will impact significantly on its immunodominance. In this study, we present evidence that the selectivity of CD4 T cell responses to peptides contained within protein Ags is not detectably influenced by the location of the peptide in a given protein or the primary sequence of the protein that bears the test peptide. We have used molecular approaches to change the location of peptides within complex protein Ags and to change the flanking sequences that border the peptide epitope to now include a protease site, and find that immunodominance or crypticity of a peptide observed in its native protein context is preserved. Collectively, these results suggest immunodominance of peptides contained in complex Ags is due to an intrinsic factor of the peptide, based upon the affinity of that peptide for MHC class II molecules. These findings are discussed with regard to implications for vaccine design.     

Biosafety, biodiversity and significance of Microbial Resource Centers (MRCs) in microbiology education

Summary Interest in the intrinsic behavior of microorganisms has led to the establishment of centers of expertise, known as Microbial Resource Centers (MRCs) built around specialized collections of cultures of microorganisms. Their main function is to accession, preserve and distribute authenticated, viable samples of microorganisms in consultation with the international scientific community for study and application. Microorganisms, which are exceptionally diverse, are found almost everywhere and affect human society in countless ways. Thus, modern microbiology has a great impact on medicine, agriculture, food science, ecology, genetics, biochemistry and many other fields. MRCs appear to be equally important to industry, to academia, and from the elementary to high school science teachers who can order specific educational strains. The basic microbiological knowledge of human society possesses the potential to revolutionize many aspects of human life. MRCs are a key resource to underpin these developments.     

Sensitivity studies for specific binding reactions using the biotin/streptavidin system by evanescent optical methods

The combination of various evanescent optical methods such as surface plasmon spectroscopy, waveguide mode spectroscopy and an integrated optical Mach-Zehnder-interferometer are used to characterize biotinylated self-assembled monolayers as well as the binding of streptavidin to these labels. The aim of designing a highly specific and sensitive, re-usable affinity sensor for antigens on the basis of an integrated optical Mach-Zehnder interferometer is based on a proper understanding of the characteristics of the entire binding matrix architecture. Therefore, a variety of biotin-derivatives immobilized in a monolayer are investigated with respect to their affinity to streptavidin and the possibility to remove the steptavidin layer specifically. The density of the streptavidin layer as well as the optical constants of the involved molecules are measured. Finally the integrated optical Mach-Zehnder interferometer is tested with respect to the sensitivity to an antigen-antibody binding reaction. An attempt to further increase the sensitivity by simultaneous detection of a fluorescence signal failed due to bleaching effects.