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

Optical application and measurement of torque on microparticles of isotropic nonabsorbing material

We show how it is possible to controllably rotate or align microscopic particles of isotropic nonabsorbing material in a TEM00 Gaussian beam trap, with simultaneous measurement of the applied torque using purely optical means. This is a simple and general method of rotation, requiring only that the particle is elongated along one direction. Thus, this method can be used to rotate or align a wide range of naturally occurring particles. The ability to measure the applied torque enables the use of this method as a quantitative tool--the rotational equivalent of optical tweezers based force measurement. As well as being of particular value for the rotation of biological specimens, this method is also suitable for the development of optically-driven micromachines.Comment: 8 pages, 6 figure

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

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

Educational Priorities for Children with Cri-Du-Chat Syndrome

There are few data on the educational needs of children with cri-du-chat syndrome: a neurodevelopmental disorder that affects learning and development. We therefore designed an Internet survey to identify parents’ educational priorities in relation to children’s level of need/ability. The survey listed 54 skills/behaviors (e.g., toileting, expresses wants and needs, and tantrums) representing 10 adaptive behavior domains (e.g., self-care, communication, and problem behavior). Parents rated their child’s current level of ability/performance with respect to each skill/behavior and indicated the extent to which training/treatment was a priority. Fifty-four surveys were completed during the 3-month data collection period. Parents identified nine high priority skills/behaviors. Results supported the view that parent priorities are often based on the child’s deficits and emergent skills, rather than on child strengths. Implications for educational practice include the need for competence to develop high priority skills/behaviors and the value of assessing children’s deficits and emergent skills to inform the content of individualized education plans

Dural plasmacytoma mimicking meningioma in a young patient with multiple myeloma

Intracranial involvement in multiple myeloma (MM) is rarely found, especially with dural involvement. There are only a few cases found concerning MM with intracranial involvement. MM usually involves an older group of patients. Cases involving young patients are very rare. The differential diagnosis of a dural plasmacytoma includes meningioma, metastasis, lymphoma and sarcoma of the dura mater. We present a young patient, 33 years old, with MM presenting an intracerebral mass mimicking meningioma on MRI. MM was diagnosed the previous year. The patient presented with headache, balance disturbance and back pain. MRI revealed an occipital extra-axial mass with a dural tail. Histopathological examination after excision showed MM. Published literatures on intracranial involvement of MM are also discussed. Plasmacytoma should be considered in the differential diagnosis of a solitary dural mass, particularly in a patient with MM

Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients.</p> <p>Methods/Design</p> <p>This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation.</p> <p>Discussion</p> <p>This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin. We showed in a previous study that metformin suppressed the formation of human colorectal ACF. We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps.</p> <p>Trial registration</p> <p>This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as <a href="http://www.clinicaltrials.gov/ct2/show/UMIN000006254">UMIN000006254</a></p

[SWI+], the Prion Formed by the Chromatin Remodeling Factor Swi1, Is Highly Sensitive to Alterations in Hsp70 Chaperone System Activity

The yeast prion [SWI+], formed of heritable amyloid aggregates of the Swi1 protein, results in a partial loss of function of the SWI/SNF chromatin-remodeling complex, required for the regulation of a diverse set of genes. Our genetic analysis revealed that [SWI+] propagation is highly dependent upon the action of members of the Hsp70 molecular chaperone system, specifically the Hsp70 Ssa, two of its J-protein co-chaperones, Sis1 and Ydj1, and the nucleotide exchange factors of the Hsp110 family (Sse1/2). Notably, while all yeast prions tested thus far require Sis1, [SWI+] is the only one known to require the activity of Ydj1, the most abundant J-protein in yeast. The C-terminal region of Ydj1, which contains the client protein interaction domain, is required for [SWI+] propagation. However, Ydj1 is not unique in this regard, as another, closely related J-protein, Apj1, can substitute for it when expressed at a level approaching that of Ydj1. While dependent upon Ydj1 and Sis1 for propagation, [SWI+] is also highly sensitive to overexpression of both J-proteins. However, this increased prion-loss requires only the highly conserved 70 amino acid J-domain, which serves to stimulate the ATPase activity of Hsp70 and thus to stabilize its interaction with client protein. Overexpression of the J-domain from Sis1, Ydj1, or Apj1 is sufficient to destabilize [SWI+]. In addition, [SWI+] is lost upon overexpression of Sse nucleotide exchange factors, which act to destabilize Hsp70's interaction with client proteins. Given the plethora of genes affected by the activity of the SWI/SNF chromatin-remodeling complex, it is possible that this sensitivity of [SWI+] to the activity of Hsp70 chaperone machinery may serve a regulatory role, keeping this prion in an easily-lost, meta-stable state. Such sensitivity may provide a means to reach an optimal balance of phenotypic diversity within a cell population to better adapt to stressful environments

Human Cancer Protein-Protein Interaction Network: A Structural Perspective

Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network). The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%). We illustrate the interface related affinity properties of two cancer-related hub proteins: Erbb3, a multi interface, and Raf1, a single interface hub. The results reveal that affinity of interactions of the multi-interface hub tends to be higher than that of the single-interface hub. These findings might be important in obtaining new targets in cancer as well as finding the details of specific binding regions of putative cancer drug candidates