FReD: the Floral Reflectance Database - a web portal for analyses of flower colour

Background: Flower colour is of great importance in various fields relating to floral biology and pollinator behaviour. However, subjective human judgements of flower colour may be inaccurate and are irrelevant to the ecology and vision of the flower's pollinators. For precise, detailed information about the colours of flowers, a full reflectance spectrum for the flower of interest should be used rather than relying on such human assessments. Methodology/Principal Findings: The Floral Reflectance Database (FReD) has been developed to make an extensive collection of such data available to researchers. It is freely available at http://www.reflectance.co.uk. The database allows users to download spectral reflectance data for flower species collected from all over the world. These could, for example, be used in modelling interactions between pollinator vision and plant signals, or analyses of flower colours in various habitats. The database contains functions for calculating flower colour loci according to widely-used models of bee colour space, reflectance graphs of the spectra and an option to search for flowers with similar colours in bee colour space. Conclusions/Significance: The Floral Reflectance Database is a valuable new tool for researchers interested in the colours of flowers and their association with pollinator colour vision, containing raw spectral reflectance data for a large number of flower species

Forty years studying British politics : the decline of Anglo-America

The still present belief some 40 years ago that British politics was both exceptional and superior has been replaced by more theoretically sophisticated analyses based on a wider and more rigorously deployed range of research techniques, although historical analysis appropriately remains important. The American influence on the study of British politics has declined, but the European Union dimension has not been fully integrated. The study of interest groups has been in some respects a fading paradigm, but important questions related to democratic health have still to be addressed. Public administration has been supplanted by public policy, but economic policy remains under-studied. A key challenge for the future is the study of the management of expectations

APOE Genotype-Function Relationship: Evidence of −491 A/T Promoter Polymorphism Modifying Transcription Control but Not Type 2 Diabetes Risk

BACKGROUND: The apolipoprotein E gene (APOE) coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP) of the APOE promoter has also been shown to modify the risk of Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE -491A/T (rs449647) polymorphism on gene transcription was accessed by dual-luciferase reporter gene assays. The -491 A to T substitution decreased the activity (p<0.05) of the cloned APOE promoter (-1017 to +406). Using the -501 to -481 nucleotide sequence of the APOE promoter as a 'bait' to screen the human brain cDNA library by yeast one-hybrid system yielded ATF4, an endoplasmic reticulum stress response gene, as one of the interacting factors. Electrophoretic-mobility-shift assays (EMSA) and chromatin immuno-precipitation (ChIP) analyses further substantiated the physical interaction between ATF4 and the APOE promoter. Over-expression of ATF4 stimulated APOE expression whereas siRNA against ATF4 suppressed the expression of the gene. However, interaction between APOE promoter and ATF4 was not -491A/T-specific. At physiological level, the genotype-function relationship of APOE promoter polymorphism was studied in type 2 diabetes. In 630 cases and 595 controls, three APOE promoter SNPs -491A/T, -219G/T (rs405509), and +113G/C (rs440446) were genotyped and tested for association with type 2 diabetes in Hong Kong Chinese. No SNP or haplotype association with type 2 diabetes was detected. CONCLUSIONS/SIGNIFICANCE: At molecular level, polymorphism -491A/T and ATF4 elicit independent control of APOE gene expression. At physiological level, no genotype-risk association was detected between the studied APOE promoter SNPs and type 2 diabetes in Hong Kong Chinese

Role of the Lateral Paragigantocellular Nucleus in the Network of Paradoxical (REM) Sleep: An Electrophysiological and Anatomical Study in the Rat

The lateral paragigantocellular nucleus (LPGi) is located in the ventrolateral medulla and is known as a sympathoexcitatory area involved in the control of blood pressure. In recent experiments, we showed that the LPGi contains a large number of neurons activated during PS hypersomnia following a selective deprivation. Among these neurons, more than two-thirds are GABAergic and more than one fourth send efferent fibers to the wake-active locus coeruleus nucleus. To get more insight into the role of the LPGi in PS regulation, we combined an electrophysiological and anatomical approach in the rat, using extracellular recordings in the head-restrained model and injections of tracers followed by the immunohistochemical detection of Fos in control, PS-deprived and PS-recovery animals. With the head-restrained preparation, we showed that the LPGi contains neurons specifically active during PS (PS-On neurons), neurons inactive during PS (PS-Off neurons) and neurons indifferent to the sleep-waking cycle. After injection of CTb in the facial nucleus, the neurons of which are hyperpolarized during PS, the largest population of Fos/CTb neurons visualized in the medulla in the PS-recovery condition was observed in the LPGi. After injection of CTb in the LPGi itself and PS-recovery, the nucleus containing the highest number of Fos/CTb neurons, moreover bilaterally, was the sublaterodorsal nucleus (SLD). The SLD is known as the pontine executive PS area and triggers PS through glutamatergic neurons. We propose that, during PS, the LPGi is strongly excited by the SLD and hyperpolarizes the motoneurons of the facial nucleus in addition to local and locus coeruleus PS-Off neurons, and by this means contributes to PS genesis

Finding the needle in the haystack: why high-throughput screening is good for your health

High-throughput screening is an essential component of the toolbox of modern technologies that improve speed and efficiency in contemporary cancer drug development. This is particularly important as we seek to exploit, for maximum therapeutic benefit, the large number of new molecular targets emerging from the Human Genome Project and cancer genomics. Screening of diverse collections of low molecular weight compounds plays a key role in providing chemical starting points for iterative optimisation by medicinal chemistry. Examples of successful drug discovery programmes based on high-throughput screening are described, and these offer potential in the treatment of breast cancer and other malignancies

Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer

BACKGROUND: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6β1, α3β1 integrins, and E-cadherin. METHODS: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. RESULTS: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6β1 (35%), α3β1 staining (60%). CONCLUSION: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types

Learning to Use Illumination Gradients as an Unambiguous Cue to Three Dimensional Shape

The luminance and colour gradients across an image are the result of complex interactions between object shape, material and illumination. Using such variations to infer object shape or surface colour is therefore a difficult problem for the visual system. We know that changes to the shape of an object can affect its perceived colour, and that shading gradients confer a sense of shape. Here we investigate if the visual system is able to effectively utilise these gradients as a cue to shape perception, even when additional cues are not available. We tested shape perception of a folded card object that contained illumination gradients in the form of shading and more subtle effects such as inter-reflections. Our results suggest that observers are able to use the gradients to make consistent shape judgements. In order to do this, observers must be given the opportunity to learn suitable assumptions about the lighting and scene. Using a variety of different training conditions, we demonstrate that learning can occur quickly and requires only coarse information. We also establish that learning does not deliver a trivial mapping between gradient and shape; rather learning leads to the acquisition of assumptions about lighting and scene parameters that subsequently allow for gradients to be used as a shape cue. The perceived shape is shown to be consistent for convex and concave versions of the object that exhibit very different shading, and also similar to that delivered by outline, a largely unrelated cue to shape. Overall our results indicate that, although gradients are less reliable than some other cues, the relationship between gradients and shape can be quickly assessed and the gradients therefore used effectively as a visual shape cue

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family