InCoB2010 - 9thInternational Conference on Bioinformatics at Tokyo, Japan, September 26-28, 2010

10.1186/1471-2105-11-S7-S1BMC Bioinformatics11SUPPL. 7-BBMI

Non-Parametric Approximations for Anisotropy Estimation in Two-dimensional Differentiable Gaussian Random Fields

Spatially referenced data often have autocovariance functions with elliptical isolevel contours, a property known as geometric anisotropy. The anisotropy parameters include the tilt of the ellipse (orientation angle) with respect to a reference axis and the aspect ratio of the principal correlation lengths. Since these parameters are unknown a priori, sample estimates are needed to define suitable spatial models for the interpolation of incomplete data. The distribution of the anisotropy statistics is determined by a non-Gaussian sampling joint probability density. By means of analytical calculations, we derive an explicit expression for the joint probability density function of the anisotropy statistics for Gaussian, stationary and differentiable random fields. Based on this expression, we obtain an approximate joint density which we use to formulate a statistical test for isotropy. The approximate joint density is independent of the autocovariance function and provides conservative probability and confidence regions for the anisotropy parameters. We validate the theoretical analysis by means of simulations using synthetic data, and we illustrate the detection of anisotropy changes with a case study involving background radiation exposure data. The approximate joint density provides (i) a stand-alone approximate estimate of the anisotropy statistics distribution (ii) informed initial values for maximum likelihood estimation, and (iii) a useful prior for Bayesian anisotropy inference.Comment: 39 pages; 8 figure

Nature's Swiss Army Knives: Ovipositor Structure Mirrors Ecology in a Multitrophic Fig Wasp Community

Resource partitioning is facilitated by adaptations along niche dimensions that range from morphology to behaviour. The exploitation of hidden resources may require specially adapted morphological or sensory tools for resource location and utilisation. Differences in tool diversity and complexity can determine not only how many species can utilize these hidden resources but also how they do so.The sclerotisation, gross morphology and ultrastructure of the ovipositors of a seven-member community of parasitic wasps comprising of gallers and parasitoids developing within the globular syconia (closed inflorescences) of Ficus racemosa (Moraceae) was investigated. These wasps also differ in their parasitism mode (external versus internal oviposition) and their timing of oviposition into the expanding syconium during its development. The number and diversity of sensilla, as well as ovipositor teeth, increased from internally ovipositing to externally ovipositing species and from gallers to parasitoids. The extent of sclerotisation of the ovipositor tip matched the force required to penetrate the syconium at the time of oviposition of each species. The internally ovipositing pollinator had only one type of sensillum and a single notch on the ovipositor tip. Externally ovipositing species had multiple sensilla types and teeth on their ovipositors. Chemosensilla were most concentrated at ovipositor tips while mechanoreceptors were more widely distributed, facilitating the precise location of hidden hosts in these wasps which lack larval host-seeking behaviour. Ovipositor traits of one parasitoid differed from those of its syntopic galler congeners and clustered with those of parasitoids within a different wasp subfamily. Thus ovipositor tools can show lability based on adaptive necessity, and are not constrained by phylogeny.Ovipositor structure mirrored the increasingly complex trophic ecology and requirements for host accessibility in this parasite community. Ovipositor structure could be a useful surrogate for predicting the biology of parasites in other communities

Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress in Human Prostate Cancer Cells by n-butylidenephthalide

BACKGROUND: N-butylidenephthalide (BP) exhibits antitumor effect in a variety of cancer cell lines. The objective of this study was to obtain additional insights into the mechanisms involved in BP induced cell death in human prostate cancer cells. METHODS/PRINCIPAL FINDINGS: Two human prostate cancer cell lines, PC-3 and LNCaP, were treated with BP, and subsequently evaluated for their viability and cell cycle profiles. BP caused cell cycle arrest and cell death in both cell lines. The G0/G1 phase arrest was correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To determine the mechanisms of BP-induced growth arrest and cell death in prostate cancer cell lines, we performed a microarray study to identify alterations in gene expression induced by BP in the LNCaP cells. Several BP-induced genes, including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated gene, were identified. BP-induced ER stress was evidenced by increased expression of the downstream molecules GRP78/BiP, IRE1-α and GADD153/CHOP in both cell lines. Blockage of IRE1-α or GADD153/CHOP expression by siRNA significantly reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2 signaling by JNK siRNA resulted in decreased expression of IRE1-α and GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18 days of treatment. CONCLUSIONS: Our results suggest that BP can cause G0/G1 phase arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress induction. Thus, BP may serve as an anticancer agent by inducing ER stress in prostate cancer

Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype

Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial

<p>Abstract</p> <p>Background</p> <p>As the worldwide dietary pattern becomes more westernized, the metabolic syndrome is reaching epidemic proportions. Lifestyle modifications including diet and exercise are recommended as first-line intervention for treating metabolic syndrome. Previously, we reported that a modified Mediterranean-style, low glycemic load diet with soy protein and phytosterols had a more favorable impact than the American Heart Association Step 1 diet on cardiovascular disease (CVD) risk factors. Subsequently, we screened for phytochemicals with a history of safe use that were capable of increasing insulin sensitivity through modulation of protein kinases, and identified hops <it>rho </it>iso-alpha acid and acacia proanthocyanidins. The objective of this study was to investigate whether enhancement of a modified Mediterranean-style, low glycemic load diet (MED) with specific phytochemicals (soy protein, phytosterols, <it>rho </it>iso-alpha acids and proanthocyanidins; PED) could improve cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia.</p> <p>Methods</p> <p>Forty-nine subjects with metabolic syndrome and hypercholesterolemia, aged 25–80, entered a randomized, 2-arm, 12-week intervention trial; 23 randomized to the MED arm; 26 to the PED arm. Forty-four subjects completed at least 8 weeks [MED (<it>n </it>= 19); PED (<it>n </it>= 25)]. All subjects were instructed to follow the same aerobic exercise program. Three-day diet diaries and 7-day exercise diaries were assessed at each visit. Fasting blood samples were collected at baseline, 8 and 12 weeks for analysis.</p> <p>Results</p> <p>Both arms experienced equal weight loss (MED: -5.7 kg; PED: -5.9 kg). However, at 12 weeks, the PED arm experienced greater reductions (<it>P </it>< 0.05) in cholesterol, non-HDL cholesterol, triglycerides (TG), cholesterol/HDL and TG/HDL compared with the MED arm. Only the PED arm experienced increased HDL (<it>P </it>< 0.05) and decreased TG/HDL (<it>P </it>< 0.01), and continued reduction in apo B/apo A-I from 8 to 12 weeks. Furthermore, 43% of PED subjects vs. only 22% of MED subjects had net resolution of metabolic syndrome. The Framingham 10-year CVD risk score decreased by 5.6% in the PED arm (<it>P </it>< 0.01) and 2.9% in the MED arm (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>These results demonstrate that specific phytochemical supplementation increased the effectiveness of the modified Mediterranean-style low glycemic load dietary program on variables associated with metabolic syndrome and CVD.</p

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

Multifunctional Poly(D,L-Lactide-co-Glycolide)/ Montmorillonite (PLGA/MMT) Nanoparticles Decorated by Trastuzumab for Targeted Chemotherapy of Breast Cancer

The book provides the necessary knowledge for scientists, engineers, and master’s and PhD students who want to be well prepared to work in the fields of chemotherapeutic engineering, cancer nanotechnology, and nanomedicine, or more generally in biomedical engineering. It also provides the basic knowledge and models for people who work in cancer clinics as well as in the pharmaceutical industr