From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

Language barrier and its relationship to diabetes and diabetic retinopathy

10.1186/1471-2458-12-781BMC Public Health121

Re-evaluating a vision-related quality of life questionnaire with item response theory (IRT) and differential item functioning (DIF) analyses

Background: For the Low Vision Quality Of Life questionnaire (LVQOL) it is unknown whether the psychometric properties are satisfactory when an item response theory (IRT) perspective is considered. This study evaluates some essential psychometric properties of the LVQOL questionnaire in an IRT model, and investigates differential item functioning (DIF). Methods: Cross-sectional data were used from an observational study among visually-impaired patients (n = 296). Calibration was performed for every dimension of the LVQOL in the graded response model. Item goodness-of-fit was assessed with the S-X2-test. DIF was assessed on relevant background variables (i.e. age, gender, visual acuity, eye condition, rehabilitation type and administration type) with likelihood-ratio tests for DIF. The magnitude of DIF was interpreted by assessing the largest difference in expected scores between subgroups. Measurement precision was assessed by presenting test information curves; reliability with the index of subject separation. Results: All items of the LVQOL dimensions fitted the model. There was significant DIF on several items. For two items the maximum difference between expected scores exceeded one point, and DIF was found on multiple relevant background variables. Item 1 ‘Vision in general’ from the “Adjustment” dimension and item 24 ‘Using tools’ from the “Reading and fine work” dimension were removed. Test information was highest for the “Reading and fine work” dimension. Indices for subject separation ranged from 0.83 to 0.94. Conclusions: The items of the LVQOL showed satisfactory item fit to the graded response model; however, two items were removed because of DIF. The adapted LVQOL with 21 items is DIF-free and therefore seems highly appropriate for use in heterogeneous populations of visually impaired patients. (aut.ref.

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV

We use 106 \ipb of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an anti-top quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to \ttbar are presented. At the 95% confidence level, we exclude the existence of a leptophobic \zpr boson in a model of topcolor-assisted technicolor with mass M_{\zpr} $<$ 480 \gev for natural width $\Gamma$ = 0.012 M_{\zpr}, and M_{\zpr} $<$ 780 \gev for $\Gamma$ = 0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200

A Measurement of the Differential Dijet Mass Cross Section in p-pbar Collisions at sqrt{s}=1.8 TeV

We present a measurement of the cross section for production of two or more jets as a function of dijet mass, based on an integrated luminosity of 86 pb^-1 collected with the Collider Detector at Fermilab. Our dijet mass spectrum is described within errors by next-to-leading order QCD predictions using CTEQ4HJ parton distributions, and is in good agreement with a similar measurement from the D0 experiment.Comment: 18 pages including 2 figures and 3 tables. Submitted to Phys. Rev. D Rapid Communication

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.

The direction of research into visual disability and quality of life in glaucoma

<p>Abstract</p> <p>Background</p> <p>Glaucoma will undoubtedly impact on a person's ability to function as they go about their day-to-day life. The purpose of this study is to investigate the amount of published knowledge in quality of life (QoL) and visual disability studies for glaucoma, and make comparisons with similar research in other chronic conditions.</p> <p>Methods</p> <p>A systematic literature search of the Global Health, EMBASE Psychiatry and MEDLINE databases. Title searches for glaucoma and six other example chronic diseases were entered alongside a selection of keywords chosen to capture studies focusing on QoL and everyday task ability. These results were further filtered during a manual search of resulting abstracts. Outcomes were the number of publications per year for each disease, number relating to QoL and type of glaucoma QoL research.</p> <p>Results</p> <p>Fifteen years ago there were no published studies relating to the impact of glaucoma on QoL but by 2009 this had risen to 1.2% of all glaucoma articles. The number of papers relating to QoL as a proportion of all papers in glaucoma in the past 10 years (0.6%) is smaller than for AMD and some other disabling chronic diseases. Most QoL studies in glaucoma (82%) involve questionnaires.</p> <p>Conclusion</p> <p>QoL studies in glaucoma are increasing in number but represent a tiny minority of the total publications in glaucoma research. There are fewer QoL articles in glaucoma compared to some other disabling chronic conditions. The majority of QoL articles in glaucoma research use questionnaires; performance-based measures of visual disability may offer an additional method of determining how the disease impacts on QoL.</p

A hybrid BAC physical map of potato: a framework for sequencing a heterozygous genome

<p>Abstract</p> <p>Background</p> <p>Potato is the world's third most important food crop, yet cultivar improvement and genomic research in general remain difficult because of the heterozygous and tetraploid nature of its genome. The development of physical map resources that can facilitate genomic analyses in potato has so far been very limited. Here we present the methods of construction and the general statistics of the first two genome-wide BAC physical maps of potato, which were made from the heterozygous diploid clone RH89-039-16 (RH).</p> <p>Results</p> <p>First, a gel electrophoresis-based physical map was made by AFLP fingerprinting of 64478 BAC clones, which were aligned into 4150 contigs with an estimated total length of 1361 Mb. Screening of BAC pools, followed by the KeyMaps <it>in silico </it>anchoring procedure, identified 1725 AFLP markers in the physical map, and 1252 BAC contigs were anchored the ultradense potato genetic map. A second, sequence-tag-based physical map was constructed from 65919 whole genome profiling (WGP) BAC fingerprints and these were aligned into 3601 BAC contigs spanning 1396 Mb. The 39733 BAC clones that overlap between both physical maps provided anchors to 1127 contigs in the WGP physical map, and reduced the number of contigs to around 2800 in each map separately. Both physical maps were 1.64 times longer than the 850 Mb potato genome. Genome heterozygosity and incomplete merging of BAC contigs are two factors that can explain this map inflation. The contig information of both physical maps was united in a single table that describes hybrid potato physical map.</p> <p>Conclusions</p> <p>The AFLP physical map has already been used by the Potato Genome Sequencing Consortium for sequencing 10% of the heterozygous genome of clone RH on a BAC-by-BAC basis. By layering a new WGP physical map on top of the AFLP physical map, a genetically anchored genome-wide framework of 322434 sequence tags has been created. This reference framework can be used for anchoring and ordering of genomic sequences of clone RH (and other potato genotypes), and opens the possibility to finish sequencing of the RH genome in a more efficient way via high throughput next generation approaches.</p