Synthetic amphipathic peptides resembling apolipoproteins stimulate the release of human placental lactogen

Previous studies from our laboratory demonstrated native high density lipoproteins and apolipoproteins AI, AII, and CI, stimulate the release of human placental lactogen (hPL) from trophoblast cells in culture. To examine the mechanisms by which these apolipoproteins stimulate hPL release, we have studied hPL secretion in response to several synthetic peptide analogs of the amphipathic helical structure of the apolipoproteins. The magnitude of the stimulation of hPL release in response to the analog peptides correlated with the ability to displace apolipoproteins from high density lipoprotein and with other measures of phospholipid binding affinity such as the increase in alpha-helicity and the size of complexes formed between the peptide and phospholipid. The correlation of stimulatory ability and lipid affinity suggests that the action of the apolipoproteins on hPL release may be mediated through an interaction with plasma membrane phospholipids

Do serum biomarkers really measure breast cancer?

Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.United States. Dept. of Defense. Breast Cancer Research Program (Grant No. W81XWH-05-1-0292)National Institutes of Health (U.S.) (R01 CA-112437-01)National Institutes of Health (U.S.) (NIH CA 84955

Identification of the CRE-1 Cellulolytic Regulon in Neurospora crassa

Background: In filamentous ascomycete fungi, the utilization of alternate carbon sources is influenced by the zinc finger transcription factor CreA/CRE-1, which encodes a carbon catabolite repressor protein homologous to Mig1 from Saccharomyces cerevisiae. In Neurospora crassa, deletion of cre-1 results in increased secretion of amylase and b-galactosidase. Methodology/Principal Findings: Here we show that a strain carrying a deletion of cre-1 has increased cellulolytic activity and increased expression of cellulolytic genes during growth on crystalline cellulose (Avicel). Constitutive expression of cre-1 complements the phenotype of a N. crassa Dcre-1 strain grown on Avicel, and also results in stronger repression of cellulolytic protein secretion and enzyme activity. We determined the CRE-1 regulon by investigating the secretome and transcriptome of a Dcre-1 strain as compared to wild type when grown on Avicel versus minimal medium. Chromatin immunoprecipitation-PCR of putative target genes showed that CRE-1 binds to only some adjacent 59-SYGGRG-39 motifs, consistent with previous findings in other fungi, and suggests that unidentified additional regulatory factors affect CRE-1 binding to promoter regions. Characterization of 30 mutants containing deletions in genes whose expression level increased in a Dcre-1 strain under cellulolytic conditions identified novel genes that affect cellulase activity and protein secretion

Optimal foraging and community structure: implications for a guild of generalist grassland herbivores

A particular linear programming model is constructed to predict the diets of each of 14 species of generalist herbivores at the National Bison Range, Montana. The herbivores have body masses ranging over seven orders of magnitude and belonging to two major taxa: insects and mammals. The linear programming model has three feeding constraints: digestive capacity, feeding time and energy requirements. A foraging strategy that maximizes daily energy intake agrees very well with the observed diets. Body size appears to be an underlying determinant of the foraging parameters leading to diet selection. Species that possess digestive capacity and feeding time constraints which approach each other in magnitude have the most generalized diets. The degree that the linear programming models change their diet predictions with a given percent change in parameter values (sensitivity) may reflect the observed ability of the species to vary their diets. In particular, the species which show the most diet variability are those whose diets tend to be balanced between monocots and dicots. The community-ecological parameters of herbivore body-size ranges and species number can possibly be related to foraging behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47765/1/442_2004_Article_BF00377109.pd

Are solitary and gregarious Mormon crickets (<em>Anabrus simplex</em>, Orthoptera, Tettigoniidae) genetically distinct?

Phase polyphenisms are usually thought to reflect plastic responses of species, independent of genetic differences; however, phase differences could correlate with genetic differentiation for various reasons. Mormon crickets appear to occur in two phases that differ in morphology and behaviour. Solitary individuals are cryptic and sedentary whereas gregarious individuals form bands, migrate, and are aposematically coloured. These traits have been thought to be phenotypically plastic and induced by environmental conditions. However, there has been no previous investigation of the extent of genetic differences between solitary and gregarious populations of this widespread North American species. We sequenced two mitochondrial genes, COII and COIII, in samples of Mormon crickets from gregarious populations west of the continental divide and solitary mountain populations primarily east of the divide. Sequencing revealed two genetically distinct clades that broadly correspond with the solitary eastern populations and the mainly gregarious western populations. We used coalescent modelling to test the hypothesis that the species consists of two deep genetic clades, as opposed to a series of equally distinct populations. Results allowed us to reject the null hypothesis that a radiation independent of phase produced these clades, and molecular clock estimates indicate the time of divergence to be approximately 2 million years ago. This work establishes that the solitary populations found in the mountains on the eastern slope are part of a clade that is genetically distinct from the western populations, which are primarily gregarious, and the implications of this apparent correlation between phase and genetic differentiation are discussed.</p