The development of a knowledge base for basic active structures: an example case of dopamine agonists

<p>Abstract</p> <p>Background</p> <p>Chemical compounds affecting a bioactivity can usually be classified into several groups, each of which shares a characteristic substructure. We call these substructures "basic active structures" or BASs. The extraction of BASs is challenging when the database of compounds contains a variety of skeletons. Data mining technology, associated with the work of chemists, has enabled the systematic elaboration of BASs.</p> <p>Results</p> <p>This paper presents a BAS knowledge base, BASiC, which currently covers 46 activities and is available on the Internet. We use the dopamine agonists D1, D2, and Dauto as examples and illustrate the process of BAS extraction. The resulting BASs were reasonably interpreted after proposing a few template structures.</p> <p>Conclusions</p> <p>The knowledge base is useful for drug design. Proposed BASs and their supporting structures in the knowledge base will facilitate the development of new template structures for other activities, and will be useful in the design of new lead compounds via reasonable interpretations of active structures.</p

Structural analysis of three novel trisaccharides isolated from the fermented beverage of plant extracts

<p>Abstract</p> <p>Background</p> <p>A fermented beverage of plant extracts was prepared from about fifty kinds of vegetables and fruits. Natural fermentation was carried out mainly by lactic acid bacteria (<it>Leuconostoc </it>spp.) and yeast (<it>Zygosaccharomyces </it>spp. and <it>Pichia </it>spp.). We have previously examined the preparation of novel four trisaccharides from the beverage: <it>O</it>-β-D-fructopyranosyl-(2->6)-<it>O</it>-β-D-glucopyranosyl-(1->3)-D-glucopyranose, <it>O</it>-β-D-fructopyranosyl-(2->6)-<it>O</it>-[β-D-glucopyranosyl-(1->3)]-D-glucopyranose, <it>O</it>-β-D-glucopyranosyl-(1->1)-<it>O</it>-β-D-fructofuranosyl-(2<->1)-α-D-glucopyranoside and <it>O</it>-β-D-galactopyranosyl-(1->1)-<it>O</it>-β-D-fructofuranosyl-(2<->1)- α-D-glucopyranoside.</p> <p>Results</p> <p>Three further novel oligosaccharides have been found from this beverage and isolated from the beverage using carbon-Celite column chromatography and preparative high performance liquid chromatography. Structural confirmation of the saccharides was provided by methylation analysis, MALDI-TOF-MS and NMR measurements.</p> <p>Conclusion</p> <p>The following novel trisaccharides were identified: <it>O</it>-β-D-fructofuranosyl-(2->1)-<it>O</it>-[β-D-glucopyranosyl-(1->3)]-β-D-glucopyranoside (named "3^G-β-D-glucopyranosyl β, β-isosucrose"), <it>O</it>-β-D-glucopyranosyl-(1->2)-<it>O</it>-[β-D-glucopyranosyl-(1->4)]-D-glucopyranose (4¹-β-D-glucopyranosyl sophorose) and <it>O</it>-β-D-fructofuranosyl-(2->6)-<it>O</it>-β-D-glucopyranosyl-(1->3)-D-glucopyranose (6²-β-D-fructofuranosyl laminaribiose).</p

When Anomaly Mediation is UV Sensitive

Despite its successes---such as solving the supersymmetric flavor problem---anomaly mediated supersymmetry breaking is untenable because of its prediction of tachyonic sleptons. An appealing solution to this problem was proposed by Pomarol and Rattazzi where a threshold controlled by a light field deflects the anomaly mediated supersymmetry breaking trajectory, thus evading tachyonic sleptons. In this paper we examine an alternate class of deflection models where the non-supersymmetric threshold is accompanied by a heavy, instead of light, singlet. The low energy form of this model is the so-called extended anomaly mediation proposed by Nelson and Weiner, but with potential for a much higher deflection threshold. The existence of this high deflection threshold implies that the space of anomaly mediated supersymmetry breaking deflecting models is larger than previously thought.Comment: 14 pages, 1 figure (version to appear in JHEP

Primary osteosarcoma of the urinary bladder treated with external radiotherapy in a patient with a history of transitional cell carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary osteosarcoma is one of the rare tumors affecting the urinary bladder. The occurrence of osteosarcoma in a patient with a long history of transitional cell carcinoma of the bladder is even more uncommon.</p> <p>Case presentation</p> <p>We present the case of a 74-year-old Greek man who was diagnosed with osteosarcoma 10 years after he had been diagnosed with transitional cell carcinoma of the bladder from which he had been free from recurrences for the past three years. Our patient was treated for the osteosarcoma with transurethral resection of bladder tumor and external beam radiation therapy. He died eight months after the diagnosis, suffering poor quality of life in the last months.</p> <p>Conclusion</p> <p>Osteosarcoma of the bladder has a dismal prognosis. External beam radiation therapy as an adjunct to transurethral resection of bladder tumor not only provides no benefit to patients with primary osteosarcoma of urinary bladder, but also may be associated with poor quality of life.</p

Diffusion of Myosin V on Microtubules: A Fine-Tuned Interaction for Which E-Hooks Are Dispensable

Organelle transport in eukaryotes employs both microtubule and actin tracks to deliver cargo effectively to their destinations, but the question of how the two systems cooperate is still largely unanswered. Recently, in vitro studies revealed that the actin-based processive motor myosin V also binds to, and diffuses along microtubules. This biophysical trick enables cells to exploit both tracks for the same transport process without switching motors. The detailed mechanisms underlying this behavior remain to be solved. By means of single molecule Total Internal Reflection Microscopy (TIRFM), we show here that electrostatic tethering between the positively charged loop 2 and the negatively charged C-terminal E-hooks of microtubules is dispensable. Furthermore, our data indicate that in addition to charge-charge interactions, other interaction forces such as non-ionic attraction might account for myosin V diffusion. These findings provide evidence for a novel way of myosin tethering to microtubules that does not interfere with other E-hook-dependent processes

Volume Regulated Anion Channel Currents of Rat Hippocampal Neurons and Their Contribution to Oxygen-and-Glucose Deprivation Induced Neuronal Death

Volume-regulated anion channels (VRAC) are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM) and NPPB (100 µM), but not to tamoxifen (10 µM). Using oxygen-and-glucose deprivation (OGD) to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD) that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX) and NMDA (40 µM AP-5) receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage

Presence of genes for type III secretion system 2 in Vibrio mimicus strains

<p>Abstract</p> <p>Background</p> <p>Vibrios, which include more than 100 species, are ubiquitous in marine and estuarine environments, and several of them e.g. <it>Vibrio cholerae</it>, <it>V. parahaemolyticus</it>, <it>V. vulnificus </it>and <it>V. mimicus</it>, are pathogens for humans. Pathogenic <it>V. parahaemolyticus </it>strains possess two sets of genes for type III secretion system (T3SS), T3SS1 and T3SS2. The latter are critical for virulence of the organism and be classified into two distinct phylogroups, T3SS2α and T3SS2β, which are reportedly also found in pathogenic <it>V. cholerae </it>non-O1/non-O139 serogroup strains. However, whether T3SS2-related genes are present in other <it>Vibrio </it>species remains unclear.</p> <p>Results</p> <p>We therefore examined the distribution of the genes for T3SS2 in vibrios other than <it>V. parahaemolyticus </it>by using a PCR assay targeting both T3SS2α and T3SS2β genes. Among the 32 <it>Vibrio </it>species tested in our study, several T3SS2-related genes were detected in three species, <it>V. cholerae</it>, <it>V. mimicus </it>and <it>V. hollisae</it>, and most of the essential genes for type III secretion were present in T3SS2-positive <it>V. cholerae </it>and <it>V. mimicus </it>strains. Moreover, both <it>V. mimicus </it>strains possessing T3SS2α and T3SS2β were identified. The gene organization of the T3SS2 gene clusters in <it>V. mimicus </it>strains was fundamentally similar to that of <it>V. parahaemolyticus </it>and <it>V. cholerae </it>in both T3SS2α- and T3SS2β-possessing strains.</p> <p>Conclusions</p> <p>This study is the first reported evidence of the presence of T3SS2 gene clusters in <it>V. mimicus </it>strains. This finding thus provides a new insight into the pathogenicity of the <it>V. mimicus </it>species.</p

Noiseonomics: The relationship between ambient noise levels in the sea and global economic trends

In recent years, the topic of noise in the sea and its effects on marine mammals has attracted considerable attention from both the scientific community and the general public. Since marine mammals rely heavily on acoustics as a primary means of communicating, navigating, and foraging in the ocean, any change in their acoustic environment may have an impact on their behavior. Specifically, a growing body of literature suggests that low-frequency, ambient noise levels in the open ocean increased approximately 3.3 dB per decade during the period 1950–2007. Here we show that this increase can be attributed primarily to commercial shipping activity, which in turn, can be linked to global economic growth. As a corollary, we conclude that ambient noise levels can be directly related to global economic conditions. We provide experimental evidence supporting this theory and discuss its implications for predicting future noise levels based on global economic trends

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Peccei-Quinn invariant extension of the NMSSM

We study a Peccei-Quinn invariant extension of the next-to-minimal supersymmetric Standard Model (NMSSM), which turns out to be free from the tadpole and domain wall problems. Having a non-renormalizable coupling to the axion superfield, the SM singlet added to the Higgs sector can naturally generate an effective Higgs mu term around the weak scale. In the model, the lightest neutralino is dominated by the singlino, which gets a mass only through mixing with the neutral Higgsinos. We explore the phenomenological consequences resulting from the existence of such a relatively light neutralino. The coupling of the SM singlet to the Higgs doublets is constrained by the experimental bound on the invisible Z-boson decay width. Under this constraint, we examine the properties of the SM-like Higgs boson paying attention to its mass and decays. We also demonstrate a UV completion of the model in SU(5) grand unified theory with a missing-partner mechanism.Comment: 22 pages, 3 figures; published versio