PiSite: a database of protein interaction sites using multiple binding states in the PDB

The vast accumulation of protein structural data has now facilitated the observation of many different complexes in the PDB for the same protein. Therefore, a single protein complex is not sufficient to identify their interaction sites, especially for proteins with multiple binding states or different partners, such as hub proteins. PiSite is a database that provides protein–protein interaction sites at the residue level with consideration of multiple complexes at the same time, by mapping the binding sites of all complexes containing the same protein in the PDB. PiSite provides easy web interfaces with an interactive viewer working with typical web browsers, and the different binding modes can be checked visually. All of the information can also be downloaded for further analyses. In addition, PiSite provides a list of proteins with multiple binding partners and multiple binding states, as well as up-to-date statistics of protein–protein interfaces. PiSite is available at http://pisite.hgc.j

Gastric Varices with Remarkable Collateral Veins in Valpronic Acid-Induced Chronic Pancreatitis

Valproic acid (VPA) is a commonly prescribed and approved treatment for epilepsy, including Angelman syndrome, throughout the world. However, the long-term administration of drugs like VPA is associated with the possible development of gastric varices and splenic obstruction as a result of chronic pancreatitis. Such cases can be difficult to treat using endoscopy or interventional radiology because of hemodynamic abnormalities; therefore, surgical treatment is often necessary

On the determination of a cloud condensation nuclei from satellite : Challenges and possibilities

We use aerosol size distributions measured in the size range from 0.01 to 10+ μm during Transport and Chemical Evolution over the Pacific (TRACE-P) and Aerosol Characterization Experiment-Asia (ACE-Asia), results of chemical analysis, measured/modeled humidity growth, and stratification by air mass types to explore correlations between aerosol optical parameters and aerosol number concentration. Size distributions allow us to integrate aerosol number over any size range expected to be effective cloud condensation nuclei (CCN) and to provide definition of a proxy for CCN (CCNproxy). Because of the internally mixed nature of most accumulation mode aerosol and the relationship between their measured volatility and solubility, this CCNproxy can be linked to the optical properties of these size distributions at ambient conditions. This allows examination of the relationship between CCNproxy and the aerosol spectral radiances detected by satellites. Relative increases in coarse aerosol (e.g., dust) generally add only a few particles to effective CCN but significantly increase the scattering detected by satellite and drive the Angstrom exponent (α) toward zero. This has prompted the use of a so-called aerosol index (AI) on the basis of the product of the aerosol optical depth and the nondimensional α, both of which can be inferred from satellite observations. This approach biases the AI to be closer to scattering values generated by particles in the accumulation mode that dominate particle number and is therefore dominated by sizes commonly effective as CCN. Our measurements demonstrate that AI does not generally relate well to a measured proxy for CCN unless the data are suitably stratified. Multiple layers, complex humidity profiles, dust with very low α mixed with pollution, and size distribution differences in pollution and biomass emissions appear to contribute most to method limitations. However, we demonstrate that these characteristic differences result in predictable influences on AI. These results suggest that inference of CCN from satellites will be challenging, but new satellite and model capabilities could possibly be integrated to improve this retrieval

Interplay between Coulomb Blockade and Resonant Tunneling studied by the Keldysh Green's Function Method

A theory of tunneling through a quantum dot is presented which enables us to study combined effects of Coulomb blockade and discrete energy spectrum of the dot. The expression of tunneling current is derived from the Keldysh Green's function method, and is shown to automatically satisfy the conservation at DC current of both junctions.Comment: 4 pages, 3 figures(mail if you need), use revtex.sty, error corrected, changed titl

Multiple myeloma presenting as an intracranial plasmacytoma: a case report

Multiple myeloma presenting as an intracranial tumor (plasmacytoma) is very rare. An 81-year-old woman was admitted to our hospital because of gait disturbance. A blood laboratory test revealed a mildly increased lactate dehydrogenase (236 IU/L) and glucose (121 mg/dl). Blood protein fractions were normal. Brain computed tomography and magnetic resonance imaging revealed an intracranial mass (5 × 4 × 3 cm) in the brain base next to the clavus, and it was clinically diagnosed as chordoma. An excision of the brain tumor was performed. Imaging modalities including ultrasound, x-ray, computed tomography, magnetic resonance imaging and positron emission tomography did not reveal any tumors other than the brain tumor. The tumor was soft, fragile, and bloody. Microscopically, a monotonous proliferation of atypical plasma cells with hyperchromatic nuclei was recognized. Histochemically, the tumor cells were pyroninophilic and the congo-red stain revealed amyloidosis. Immunohistochemically, the tumor cells were positive for κ-chain and negative for cytokeratin, epithelial membrane antigen, vimentin, CD45, CD20, CD45RO, λ-chain, IgM, IgA, IgG, synaptophysin, chromogranin, S100 protein, desmin, α-smooth muscle antigen, myoglobin, p53 protein, and glial fibrillary acidic protein. The Ki-67 labeling was 11%. Intracranial plasmacytoma was pathologically diagnosed. The patient was treated by adjuvant chemoradiation, and entered into the complete remission stage. However, multiple metastases emerged in the vertebral bones and ribs six months after the remission. A diagnosis of multiple myeloma was made. The urine revealed Bence-Jones protein of monoclonal IgG κ-chain type, but blood M protein was not recognized. The patient's condition gradually deteriorated. The patient died of respiratory failure due to bronchopneumonia 18 months after the admission. The present case indicates that multiple myeloma may manifest as an intracranial brain tumor (plasmacytoma)

Global 3-D distribution of aerosol composition by synergistic use of CALIOP and MODIS observations

For the observation of the global three-dimensional distribution of aerosol composition and the evaluation of the shortwave direct radiative effect (SDRE) by aerosols, we developed a retrieval algorithm that uses observation data from the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) on board the Cloud–Aerosol Lidar Infrared Pathfinder Satellite Observations (CALIPSO) satellite and the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Aqua. The CALIOP–MODIS retrieval optimizes the aerosol composition to both the CALIOP and MODIS observations in the daytime. Aerosols were assumed to be composed of four aerosol components: water-soluble (WS), light-absorbing (LA), dust (DS), and sea salt (SS) particles. The outputs of the CALIOP–MODIS retrieval are the vertical profiles of the extinction coefficient (αa), single-scattering albedo (ω0), asymmetry factor (g) of total aerosols (WS+LA+DS+SS), and αa of WS, LA, DS, and SS. Daytime observations of CALIOP and MODIS in 2010 were analyzed by the CALIOP–MODIS retrieval. The global means of the aerosol optical depth (τa) at 532 nm were 0.147±0.148 for total aerosols, 0.072±0.085 for WS, 0.027±0.035 for LA, 0.025±0.054 for DS, and 0.023±0.020 for SS. τa of the CALIOP–MODIS retrieval was between those of the CALIPSO and MODIS standard products and was close to the MODIS standard product. The global means of ω0 and g were 0.940±0.038 and 0.718±0.037; these values are in the range of those reported by previous studies. The horizontal distribution of each aerosol component was reasonable; for example, DS was large in desert regions, and LA was large in the major regions of biomass burning and anthropogenic aerosol emissions. The values of τa, ω0, g, and fine and coarse median radii of the CALIOP–MODIS retrieval were compared with those of the AERONET products. τa at 532 and 1064 nm of the CALIOP–MODIS retrieval agreed well with the AERONET products. The ω0, g, and fine and coarse median radii of the CALIOP–MODIS retrieval were not far from those of the AERONET products, but the variations were large, and the coefficients of determination for linear regression between them were small. In the retrieval results for 2010, the clear-sky SDRE values for total aerosols at the top and bottom of the atmosphere were -4.99±3.42 and -13.10±9.93 W m−2, respectively, and the impact of total aerosols on the heating rate was from 0.0 to 0.5 K d−1. These results are generally similar to those of previous studies, but the SDRE at the bottom of the atmosphere is larger than that reported previously. Consequently, comparison with previous studies showed that the CALIOP–MODIS retrieval results were reasonable with respect to aerosol composition, optical properties, and the SDRE.</p

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society

Clinical Usefulness of Multiplex PCR Lateral Flow in MRSA Detection: A Novel, Rapid Genetic Testing Method

Methicillin-resistant Staphylococcus aureus (MRSA) with exogenous cassette DNA containing the methicillin-resistant gene mecA (SCCmec) poses a problem as a drug-resistant bacterium responsible for hospital- and community-acquired infections. The frequency of MRSA detection has recently been increasing rapidly in Japan, and SCCmec has also been classified more diversely into types I–V. A rapid test is essential for early diagnosis and treatment of MRSA infections, but detection by conventional methods requires at least two days. The newly developed multiplex PCR lateral flow method allows specific amplification of femA to detect S. aureus, mecA to detect SCCmec, and kdpC to detect SCCmec type II; moreover, PCR products can be evaluated visually in about 3 h. In the present study, we developed a PCR lateral flow method for MRSA using this method and investigated its clinical usefulness in the detection of MRSA. The results showed a diagnostic concordance rate of 91.7% for MRSA and methicillin-susceptible S. aureus between bacteriological examination and PCR lateral flow, and a high level of specificity in PCR lateral flow. In addition, a higher detection rate for S. aureus using the same sample was observed for PCR lateral flow (70.2%) than for bacteriological tests (48.6%). The above results show that PCR lateral flow for MRSA detection has high sensitivity, specificity, and speed, and its clinical application as a method for early diagnosis of MRSA infections appears to be feasible

Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses

Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancerstrategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Herewe use genetic ablation of this enzyme to induce indolence in two cancer types, andshow this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha(HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inabilityto respond to hypoxia, concordantly with the persistence of human oncocytomas. Wedemonstrate that CI-deficient tumors survive and carry out angiogenesis, despite theirinability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated mac-rophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneouspharmacological inhibition of CI function through metformin and macrophage infiltrationthrough PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basisfor an efficient combinatorial adjuvant therapy in clinical trials