Increased behavioral and neuronal sensitivity to sex pheromone after brief odor experience in a moth

Plasticity in the response to stimuli related to food and oviposition cues is well documented in insects. However, responses to cues related to reproduction, for example, sex pheromones, are considered to be innate and thus not affected by experience. Here we show that brief preexposure to sex pheromones, without ensuing reward, lowers the threshold for behavioral response and augments the sensitivity in antennal lobe interneurons to pheromone compared with naive male moths. Thus, the sex pheromone system in insects can be modulated by experience. In addition, we show that the behavioral attraction to sex pheromone increases after preexposure in a time-dependent manner: a short-term effect, possibly a form of sensitization, and a long-term effect after more than 24 h. The behavioral long-term effect is paralleled by an increase in sensitivity of interneurons in the primary olfactory center, whereas the peripheral olfactory system does not change its sensitivity. We hypothesize that short-term sensitization to sex pheromone serves as a kind of alert system, whereas the long-term effect improves male performance when reproductively active females are present.     

Individualized survival and treatment response predictions for breast cancers using phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-IGF-IR/In, phospho-MAPK, and phospho-p70S6K proteins

The development and progression of breast cancer involves the activation of numerous protein kinases, and the change in phosphorylation is a hallmark of protein kinase activation. In this study, we identified a comprehensive profile to predict individual breast cancer patients' survival and treatment responses using the Random Committee algorithm. The profile incorporated a subset of phosphorylated signal protein expressions and several selected clinical factors of breast cancer. The parameters of our profile were identified by supervised feature selection algorithms, Gain Ratio Attribute Evaluation and Relief. The results showed that the overall accuracy of survival prediction reached 92.3% for individual breast cancer patients with the use of the expression profiles of phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-IGFIR/In, phospho-MAPK, and phospho-p70S6K plus the selected clinical factors. The results also indicated that the overall accuracy of treatment response prediction was 92.6% with the use of the level of phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-MAPK, and phospho-p70S6K plus the selected clinical information. The prediction system combines multiple signal protein activation profiles and relevant clinical information, and provides a unique guideline to aid individualized decision-making in the clinical management of breast cancer.     

Biochemical mechanisms leading to tryptophan 2,3-dioxygenase activation

Tryptophan 2,3-dioxygenase (TDO) is the first enzyme in the tryptophan oxidation pathway. It is a hemoprotein and its heme prosthetic group is present as a heme-ferric (heme-Fe(3+)) form that is not active. To be able to oxidize tryptophan, the heme-Fe(3+) form of the enzyme must be reduced to a heme-ferrous (heme-Fe(2+)) form and this study describes conditions that promote TDO activation. TDO is progressively activated upon mixing with tryptophan in a neutral buffer, which leads to an impression that tryptophan is responsible for TDO activation. Through extensive analysis of factors resulting in TDO activation during incubation with tryptophan, we conclude that tryptophan indirectly activates TDO through promoting the production of reactive oxygen species. This consideration is supported by the virtual elimination of the initial lag phase when either pre-incubated tryptophan solution was used as the substrate or a low concentration of superoxide or hydrogen peroxide was incorporated into the freshly tryptophan and TDO mixture. However, accumulation of these reactive oxygen species also leads to the inactivation of TDO, so that both TDO activation and inactivation proceed with the specific outcome depending greatly on the concentrations of superoxide and hydrogen peroxide. As a consequence, the rate of TDO catalysis varies depending upon the proportion of the active to inactive forms of the enzyme, which is in a dynamic relationship in the reaction mixture. These data provide some insight towards elucidating the molecular regulation of TDO in vivo.     

Molecular phylogenies and evolution of crt genes in algae

The carotenoids constitute the most widespread class of pigments in nature. Most previous work has concentrated on the identification and characterization of their chemical physical properties and bioavailability. In recent years, significant amounts of research have been conducted in an attempt to analyze the genes and the molecular regulation of the genes involved in the biosynthesis of carotenoids. However, it is important not to lose sight of the early evolution of carotenoid biosynthesis. One of the major obstacles in understanding the evolution of the respective enzymes and their patterns of selection is a lack of a well-supported phylogenic analysis. In the present research, a major long-term objective was to provide a clearer picture of the evolutionary history of genes, together with an evaluation of the patterns of selection in algae. These phylogenies will be important in studies characterizing the evolution of algae. The gene sequences of the enzymes involved in the major steps of the carotenoid biosynthetic pathway in algae (cyanobacteria, rhofophyta, chlorophyta) have been analyzed. Phylogenetic relationships among protein-coding DNA sequences were reconstructed by neighbor-joining (NJ) analysis for the respective carotenoid biosynthetic pathway genes (crt) in algae. The analysis also contains an estimation of the rate of nonsynonymous nucleotide substitutions per nonsynonymous site (d(N)), synonymous nucleotide substitution per synonymous site (d(S)), and the ratio of nonsynonmous (d(N)/d(S)) for the test of selection patterns. The phylogenetic trees show that the taxa of some genera have a closer evolutionary relationship with other genera in some gene sequences, which suggests a common ancient origin and that lateral gene transfer has occurred among unrelated genera. The d(N) values of crt genes in the early pathway are relatively low, while those of the following steps are slightly higher, while the d(N) values of crt genes in chlorophyta are higher than those in cyanobacteria. Most of the d(N)/d(S) values exceed 1. The phylogenetic analysis revealed that lateral gene transfer may have taken place across algal genomes and the d(N) values suggest that most of the early crt genes are well conserved compared to the later crt genes. Furthermore, d(N) values also revealed that the crt genes of chlorophyta are more evolutionary than cyanobacteria. The amino acids' changes are mostly adaptive evolution under the influence of positive diversity selection.     

Computerized analysis of cellular features and biomarkers for cytologic diagnosis of early lung cancer

OBJECTIVE: To present a set of novel computerized analysis algorithms to construct a computer-aided cytologic diagnosis (CACD) system to differentiate lung cancer biomarkers and identify cancer cells in the tissue-based specimen images. STUDY DESIGN: Molecular methods, including application of cancer-specific markers, may prove to be complementary to cytology diagnosis, especially when they are combined with CACD system for biomarker assessment. We trained a novel CACD system to recognize expression of the cancer biomarkers histone H2AX in lung cancer cells and then tested the accuracy of this system to distinguish resected lung cancer from preneoplastic and normal tissues. The major characteristics of CACD algorithms is to adapt detection parameters according to cellular image contents. Our newly developed wavelet transform is able to adaptively select different resolution and orientation features based on image content requirements. RESULTS: Visual, statistical and quantitative results as CACD performance evaluation are presented in this paper. CONCLUSION: The presented algorithms and CACD system for cellular feature enhancement, segmentation and classification are very important in distinguishing benign and malignant lesions.     

Transgelin functions as a suppressor via inhibition of ARA54-enhanced androgen receptor transactivation and prostate cancer cell growth

The androgen receptor (AR) requires coregulators for its optimal function. However, whether AR coregulators further need interacting protein(s) for their proper function remains unclear. Here we describe transgelin as the first ARA54-associated negative modulator for AR. Transgelin suppressed ARA54-enhanced AR function in ARA54-positive, but not in ARA54-negative, cells. Transgelin suppressed AR transactivation via interruption of ARA54 homodimerization and AR-ARA54 heterodimerization, resulting in the cytoplasmic retention of AR and ARA54. Stable transfection of transgelin in LNCaP cells suppressed AR-mediated cell growth and prostate-specific antigen expression, whereas this suppressive effect was abolished by the addition of ARA54-small interfering RNA. Results from tissue surveys showing decreased expression of transgelin in prostate cancer specimens further strengthened the suppressor role of transgelin. Our findings reveal the novel mechanisms of how transgelin functions as a suppressor to inhibit prostate cancer cell growth. They also demonstrate that AR coregulators, like ARA54, might have dual in vivo roles functioning as both a direct coactivator and as an indirect mediator in AR function. The finding that a protein can modulate AR function without direct interaction with AR might provide a new therapeutic approach, with fewer side effects, to battle prostate cancer by targeting AR indirectly.     

Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats

This study investigated the pharmacokinetic properties of crocin following oral administration in rats. After a single oral dose, crocin was undetected while crocetin, a metabolite of crocin, was found in plasma at low concentrations. Simultaneously, crocin was largely present in feces and intestinal contents within 24h. After repeated oral doses for 6 days, crocin remained undetected in plasma and plasma crocetin concentrations were comparable to the corresponding data obtained after the single oral dose. Furthermore, the absorption characteristics of crocin were evaluated in situ using an intestinal recirculation perfusion method. During recirculation, crocin was undetected and low concentrations of crocetin were detected in plasma. The concentrations of crocin in the perfusate were reduced through different intestinal segments, and the quantities of drug lost were greater throughout the colon. These results indicate that (1) orally administered crocin is not absorbed either after a single dose or repeated doses, (2) crocin is excreted largely through the intestinal tract following oral administration, (3) plasma crocetin concentrations do not tend to accumulate with repeated oral doses of crocin, and (4) the intestinal tract serves as an important site for crocin hydrolysis.     

PATJ regulates directional migration of mammalian epithelial cells

Directional migration is important in wound healing by epithelial cells. Recent studies have shown that polarity proteins such as mammalian Partitioning-defective 6 (Par6), atypical protein kinase C (aPKC) and mammalian Discs large 1 (Dlg1) are crucial not only for epithelial apico-basal polarity, but also for directional movement. Here, we show that the protein associated with Lin seven 1 (PALS1)-associated tight junction protein (PATJ), another evolutionarily conserved polarity protein, is also required for directional migration by using a wound-induced migration assay. In addition, we found that aPKC and Par3 localize to the leading edge during migration of epithelia and that PATJ regulates their localization. Furthermore, our results show that microtubule-organizing centre orientation is disrupted in PATJ RNA interference (RNAi) MDCKII (Madin-Darby canine kidney II) cells during migration. Together, our data indicate that PATJ controls directional migration by regulating the localization of aPKC and Par3 to the leading edge. The migration defect in PATJ RNAi cells seems to be due to the disorganization of the microtubule network induced by mislocalization of polarity proteins.     

Assessment of algorithms for high throughput detection of genomic copy number variation in oligonucleotide microarray data

Background

Genomic deletions and duplications are important in the pathogenesis of diseases, such as cancer and mental retardation, and have recently been shown to occur frequently in unaffected individuals as polymorphisms. Affymetrix GeneChip whole genome sampling analysis (WGSA) combined with 100 K single nucleotide polymorphism (SNP) genotyping arrays is one of several microarray-based approaches that are now being used to detect such structural genomic changes. The popularity of this technology and its associated open source data format have resulted in the development of an increasing number of software packages for the analysis of copy number changes using these SNP arrays.

Results

We evaluated four publicly available software packages for high throughput copy number analysis using synthetic and empirical 100 K SNP array data sets, the latter obtained from 107 mental retardation (MR) patients and their unaffected parents and siblings. We evaluated the software with regards to overall suitability for high-throughput 100 K SNP array data analysis, as well as effectiveness of normalization, scaling with various reference sets and feature extraction, as well as true and false positive rates of genomic copy number variant (CNV) detection.

Conclusion

We observed considerable variation among the numbers and types of candidate CNVs detected by different analysis approaches, and found that multiple programs were needed to find all real aberrations in our test set. The frequency of false positive deletions was substantial, but could be greatly reduced by using the SNP genotype information to confirm loss of heterozygosity.