IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

Two cases of possible transmitted drug-resistant HIV : likely HIV superinfection and unmasking of pre-existing resistance

In the UK, patients undergo HIV viral load and genotype testing before they are prescribed antiretroviral therapy. The genotype test guides clinicians in prescribing antiretroviral therapy with maximum efficacy against the patient’s specific viral strain. HIV viral load escape under antiretroviral drug therapy, to which the virus was thought to be genotypically susceptible, is commonly observed in patients with poor adherence. We observed early viral escapes in two-newly diagnosed patients, during antiretroviral treatment, with different sequences compared to their original viral resistance test and who reported excellent adherence to and tolerance of their therapy. HIV superinfection with a new viral strain was identified in a patient with multiple risk factors and co-infections with sexually transmitted infections. The second patient was a case of the emergence of primary resistant virus under drug pressure. Both suppressed their virus promptly after treatment switch

Surgically cured hypoglycemia secondary to pleural solitary fibrous tumour: case report and update review on the Doege-Potter syndrome

The association of paraneoplastic hypoglycemia [Doege-Potter syndrome] and finger clubbing [Pierre-Marie-Bamberg syndrome] with pleural solitary fibrous tumour is rare. We present a previously unpublished but typical example of this rare occurrence together with a detailed updated literature review of previously published cases of pleural SFT discussing the histopathology of SFT; pathophysiology of the hypoglycemia and finger clubbing; treatment and outcome of pleural SFT. The patient, a 57-year-old African male was admitted at our hospital with recurrent episodes of hypoglycemia. He was found to have digital clubbing and decreased breath sounds in the right lower chest but no other significant clinical findings. His insulin level measured during an episode of hypoglycemia was undetectable. Chest radiograph and CT-scan revealed a lobulated mass in the right chest which was diagnosed to be SFT on histology. Surgical excision of the mass resulted in cure of the hypoglycemic episodes and rapid regression of the clubbing. Less than 65 cases of pleural SFT manifesting with hypoglycemia with or without finger-clubbing have been published in the English literature. The mean diameter of these tumours manifesting with hypoglycemia is 20 cm, 54% being benign while 42% were malignant. They predominantly present in the 6th-8th decade, average age of 64 years and a slight male preponderance at 58%. Complete surgical resection remains the most important predictor of clinical outcome in terms of recurrence and metastases, while providing instant cure for the hypoglycemia and rapid resolution of the finger clubbing

High-resolution computed tomography reconstructions of invertebrate burrow systems

The architecture of biogenic structures can be highly influential in determining species contributions to major soil and sediment processes, but detailed 3-D characterisations are rare and descriptors of form and complexity are lacking. Here we provide replicate high-resolution micro-focus computed tomography (μ-CT) data for the complete burrow systems of three co-occurring, but functionally contrasting, sediment-dwelling inter-tidal invertebrates assembled alone, and in combination, in representative model aquaria. These data (≤2,000 raw image slices aquarium−1, isotropic voxel resolution, 81 μm) provide reference models that can be used for the development of novel structural analysis routines that will be of value within the fields of ecology, pedology, geomorphology, palaeobiology, ichnology and mechanical engineering. We also envisage opportunity for those investigating transport networks, vascular systems, plant rooting systems, neuron connectivity patterns, or those developing image analysis or statistics related to pattern or shape recognition. The dataset will allow investigators to develop or test novel methodology and ideas without the need to generate a complete three-dimensional computation of exemplar architecture

Memory Effects and Scaling Laws in Slowly Driven Systems

This article deals with dynamical systems depending on a slowly varying parameter. We present several physical examples illustrating memory effects, such as metastability and hysteresis, which frequently appear in these systems. A mathematical theory is outlined, which allows to show existence of hysteresis cycles, and determine related scaling laws.Comment: 28 pages (AMS-LaTeX), 18 PS figure

MTHFD1 controls DNA methylation in Arabidopsis.

DNA methylation is an epigenetic mechanism that has important functions in transcriptional silencing and is associated with repressive histone methylation (H3K9me). To further investigate silencing mechanisms, we screened a mutagenized Arabidopsis thaliana population for expression of SDCpro-GFP, redundantly controlled by DNA methyltransferases DRM2 and CMT3. Here, we identify the hypomorphic mutant mthfd1-1, carrying a mutation (R175Q) in the cytoplasmic bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (MTHFD1). Decreased levels of oxidized tetrahydrofolates in mthfd1-1 and lethality of loss-of-function demonstrate the essential enzymatic role of MTHFD1 in Arabidopsis. Accumulation of homocysteine and S-adenosylhomocysteine, genome-wide DNA hypomethylation, loss of H3K9me and transposon derepression indicate that S-adenosylmethionine-dependent transmethylation is inhibited in mthfd1-1. Comparative analysis of DNA methylation revealed that the CMT3 and CMT2 pathways involving positive feedback with H3K9me are mostly affected. Our work highlights the sensitivity of epigenetic networks to one-carbon metabolism due to their common S-adenosylmethionine-dependent transmethylation and has implications for human MTHFD1-associated diseases

Helicity at Photospheric and Chromospheric Heights

In the solar atmosphere the twist parameter $\alpha$ has the same sign as magnetic helicity. It has been observed using photospheric vector magnetograms that negative/positive helicity is dominant in the northern/southern hemisphere of the Sun. Chromospheric features show dextral/sinistral dominance in the northern/southern hemisphere and sigmoids observed in X-rays also have a dominant sense of reverse-S/forward-S in the northern/southern hemisphere. It is of interest whether individual features have one-to-one correspondence in terms of helicity at different atmospheric heights. We use UBF \Halpha images from the Dunn Solar Telescope (DST) and other \Halpha data from Udaipur Solar Observatory and Big Bear Solar Observatory. Near-simultaneous vector magnetograms from the DST are used to establish one-to-one correspondence of helicity at photospheric and chromospheric heights. We plan to extend this investigation with more data including coronal intensities.Comment: 5 pages, 1 figure, 1 table To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Dynamic compartmentalization of bacteria: accurate division in E. coli

Positioning of the midcell division plane within the bacterium E. coli is controlled by the min system of proteins: MinC, MinD and MinE. These proteins coherently oscillate from end to end of the bacterium. We present a reaction--diffusion model describing the diffusion of min proteins along the bacterium and their transfer between the cytoplasmic membrane and cytoplasm. Our model spontaneously generates protein oscillations in good agreement with experiments. We explore the oscillation stability, frequency and wavelength as a function of protein concentration and bacterial length.Comment: 4 pages, 4 figures, Latex2e, Revtex