157 research outputs found
The Epidemiology of Psoriasis in a Dermatology Clinic in a General Hospital in Port-of-Spain, Trinidad and Tobago, West Indies
ABSTRACT Psoriasis is a chronic skin disorder which is believed to affec
The DINGO dataset: a comprehensive set of data for the SAMPL challenge
Part of the latest SAMPL challenge was to predict how a small fragment library of 500 commercially available compounds would bind to a protein target. In order to assess the modellers’ work, a reasonably comprehensive set of data was collected using a number of techniques. These included surface plasmon resonance, isothermal titration calorimetry, protein crystallization and protein crystallography. Using these techniques we could determine the kinetics of fragment binding, the energy of binding, how this affects the ability of the target to crystallize, and when the fragment did bind, the pose or orientation of binding. Both the final data set and all of the raw images have been made available to the community for scrutiny and further work. This overview sets out to give the parameters of the experiments done and what might be done differently for future studies
Small-scale, semi-automated purification of eukaryotic proteins for structure determination
A simple approach that allows cost-effective automated purification of recombinant proteins in levels sufficient for functional characterization or structural studies is described. Studies with four human stem cell proteins, an engineered version of green fluorescent protein, and other proteins are included. The method combines an expression vector (pVP62K) that provides in vivo cleavage of an initial fusion protein, a factorial designed auto-induction medium that improves the performance of small-scale production, and rapid, automated metal affinity purification of His8-tagged proteins. For initial small-scale production screening, single colony transformants were grown overnight in 0.4 ml of auto-induction medium, produced proteins were purified using the Promega Maxwell 16, and purification results were analyzed by Caliper LC90 capillary electrophoresis. The yield of purified [U-15N]-His8-Tcl-1 was 7.5 μg/ml of culture medium, of purified [U-15N]-His8-GFP was 68 μg/ml, and of purified selenomethione-labeled AIA–GFP (His8 removed by treatment with TEV protease) was 172 μg/ml. The yield information obtained from a successful automated purification from 0.4 ml was used to inform the decision to scale-up for a second meso-scale (10–50 ml) cell growth and automated purification. 1H–15N NMR HSQC spectra of His8-Tcl-1 and of His8-GFP prepared from 50 ml cultures showed excellent chemical shift dispersion, consistent with well folded states in solution suitable for structure determination. Moreover, AIA–GFP obtained by proteolytic removal of the His8 tag was subjected to crystallization screening, and yielded crystals under several conditions. Single crystals were subsequently produced and optimized by the hanging drop method. The structure was solved by molecular replacement at a resolution of 1.7 Å. This approach provides an efficient way to carry out several key target screening steps that are essential for successful operation of proteomics pipelines with eukaryotic proteins: examination of total expression, determination of proteolysis of fusion tags, quantification of the yield of purified protein, and suitability for structure determination
Measuring Behavioral Regulation in Four Societies
The present study examined the psychometric properties of scores from a direct measure of behavioral regulation, the Head–Toes–Knees–Shoulders task (HTKS) with 3- to 6-year-old children in the United States, Taiwan, South Korea, and China. Specifically, we investigated (a) the nature and variability of HTKS scores, including relations to teacher-rated classroom behavioral regulation; and (b) relations between the HTKS and early mathematics, vocabulary, and literacy skills. Higher HTKS scores were significantly related to higher teacher ratings of classroom behavioral regulation in the United States and South Korea but not in Taiwan and China. Also, higher HTKS scores were significantly related to higher early mathematics, vocabulary, and literacy skills beyond the influence of demographic variables and teacher-rated classroom behavioral regulation. These initial findings suggest that HTKS scores may be interpreted as reflecting early behavioral regulation in these 4 societies and that behavioral regulation is important for early academic success in the United States and in Asian countries.The present study examined the psychometric properties of scores from a direct measure of behavioral regulation, the Head-Toes-Knees-Shoulders task (HTKS) with 3- to 6-year-old children in the United States, Taiwan, South Korea, and China. Specifically, we investigated (a) the nature and variability of HTKS scores, including relations to teacher-rated classroom behavioral regulation; and (b) relations between the HTKS and early mathematics, vocabulary, and literacy skills. Higher HTKS scores were significantly related to higher teacher ratings of classroom behavioral regulation in the United States and South Korea but not in Taiwan and China. Also, higher HTKS scores were significantly related to higher early mathematics, vocabulary, and literacy skills beyond the influence of demographic variables and teacher-rated classroom behavioral regulation. These initial findings suggest that HTKS scores may be interpreted as reflecting early behavioral regulation in these 4 societies and that behavioral regulation is important for early academic success in the United States and in Asian countries
The cryo-electron microscopy supramolecular structure of the bacterial stressosome unveils its mechanism of activation
How the stressosome, the epicenter of the stress response in bacteria, transmits stress signals from the environment has remained elusive. The stressosome consists of multiple copies of three proteins RsbR, RsbS and RsbT, a kinase that is important for its activation. Using cryo-electron microscopy, we determined the atomic organization of the Listeria monocytogenes stressosome at 3.38 Å resolution. RsbR and RsbS are organized in a 60-protomers truncated icosahedron. A key phosphorylation site on RsbR (T209) is partially hidden by an RsbR flexible loop, whose "open" or "closed" position could modulate stressosome activity. Interaction between three glutamic acids in the N-terminal domain of RsbR and the membrane-bound mini-protein Prli42 is essential for Listeria survival to stress. Together, our data provide the atomic model of the stressosome core and highlight a loop important for stressosome activation, paving the way towards elucidating the mechanism of signal transduction by the stressosome in bacteria
Mouse thymidylate synthase does not show the inactive conformation, observed for the human enzyme
Measurement of electrons from beauty-hadron decays in p-Pb collisions at root(NN)-N-S=5.02 TeV and Pb-Pb collisions at. root(NN)-N-S=2.76 TeV
The production of beauty hadrons was measured via semi-leptonic decays at mid-rapidity with the ALICE detector at the LHC in the transverse momentum interval 1<pT< 8 GeV/c in minimum-bias p-Pb collisions at sNN=5.02 TeV and in 1.3 < pT< 8 GeV/c in the 20% most central Pb-Pb collisions at sNN=2.76 TeV. The pp reference spectra at sNN=5.02 TeV and s=2.76 TeV, needed for the calculation of the nuclear modification factors RpPb and RPbPb, were obtained by a pQCD-driven scaling of the cross section of electrons from beauty-hadron decays measured at s=7 TeV. In the pT interval 3 < pT< 8 GeV/c, a suppression of the yield of electrons from beauty-hadron decays is observed in Pb-Pb compared to pp collisions. Towards lower pT, the RPbPb values increase with large systematic uncertainties. The RpPb is consistent with unity within systematic uncertainties and is well described by theoretical calculations that include cold nuclear matter effects in p-Pb collisions. The measured RpPb and these calculations indicate that cold nuclear matter effects are small at high transverse momentum also in Pb-Pb collisions. Therefore., the observed reduction of RPbPb below unity at high pT may be ascribed to an effect of the hot and dense medium formed in Pb-Pb collisions.[Figure not available: see fulltext.
- …
