1,075 research outputs found
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
On Semiclassical Limits of String States
We explore the relation between classical and quantum states in both open and
closed (super)strings discussing the relevance of coherent states as a
semiclassical approximation. For the closed string sector a gauge-fixing of the
residual world-sheet rigid translation symmetry of the light-cone gauge is
needed for the construction to be possible. The circular target-space loop
example is worked out explicitly.Comment: 12 page
Holographic Brownian Motion in Magnetic Environments
Using the gauge/gravity correspondence, we study the dynamics of a heavy
quark in two strongly-coupled systems at finite temperature: Super-Yang-Mills
in the presence of a magnetic field and non-commutative Super-Yang-Mills. In
the former, our results agree qualitatively with the expected behavior from
weakly-coupled theories. In the latter, we propose a Langevin equation that
accounts for the effects of non-commutativity and we find new interesting
features. The equation resembles the structure of Brownian motion in the
presence of a magnetic field and implies that the fluctuations along
non-commutative directions are correlated. Moreover, our results show that the
viscosity is smaller than the commutative case and that the diffusion
properties of the quark are unaffected by non-commutativity. Finally, we
compute the random force autocorrelator and verify that the
fluctuation-dissipation theorem holds in the presence of non-commutativity.Comment: 34 pages. v2: typos corrected. v3: title and abstract slightly
modified in order to better reflect the contents of the paper; footnote 3 and
one reference were also added; version accepted for publication in JHE
Gender difference in symptomatic radiographic knee osteoarthritis in the Knee Clinical Assessment – CAS(K): A prospective study in the general population
<p>Abstract</p> <p>Background</p> <p>A recent study of adults aged ≥50 years reporting knee pain found an excess of radiographic knee osteoarthritis (knee ROA) in symptomatic males compared to females. This was independent of age, BMI and other clinical signs and symptoms. Since this finding contradicts many previous studies, our objective was to explore four possible explanations for this gender difference: X-ray views, selection, occupation and non-articular conditions.</p> <p>Methods</p> <p>A community-based prospective study. 819 adults aged ≥50 years reporting knee pain in the previous 12 months were recruited by postal questionnaires to a research clinic involving plain radiography (weight-bearing posteroanterior semiflexed, supine skyline and lateral views), clinical interview and physical examination. Any knee ROA, ROA severity, tibiofemoral joint osteoarthritis (TJOA) and patellofemoral joint osteoarthritis (PJOA) were defined using all three radiographic views. Occupational class was derived from current or last job title. Proportions of each gender with symptomatic knee ROA were expressed as percentages, stratified by age; differences between genders were expressed as percentage differences with 95% confidence intervals.</p> <p>Results</p> <p>745 symptomatic participants were eligible and had complete X-ray data. Males had a higher occurrence (77%) of any knee ROA than females (61%). In 50–64 year olds, the excess in men was mild knee OA (particularly PJOA); in ≥65 year olds, the excess was both mild and moderate/severe knee OA (particularly combined TJOA/PJOA). This male excess persisted when using the posteroanterior view only (64% vs. 52%). The lowest level of participation in the clinic was symptomatic females aged 65+. Within each occupational class there were more males with symptomatic knee ROA than females. In those aged 50–64 years, non-articular conditions were equally common in both genders although, in those aged 65+, they occurred more frequently in symptomatic females (41%) than males (31%).</p> <p>Conclusion</p> <p>The excess of knee ROA among symptomatic males in this study seems unlikely to be attributable to the use of comprehensive X-ray views. Although prior occupational exposures and the presence of non-articular conditions cannot be fully excluded, selective non-participation bias seems the most likely explanation. This has implications for future study design.</p
A treatment applying a biomechanical device to the feet of patients with knee osteoarthritis results in reduced pain and improved function: a prospective controlled study
<p>Abstract</p> <p>Background</p> <p>This study examined the effect of treatment with a novel biomechanical device on the level of pain and function in patients with knee OA.</p> <p>Methods</p> <p>Patients with bilateral knee OA were enrolled to active and control groups. Patients were evaluated at baseline, at 4 weeks and at the 8-week endpoint. A novel biomechanical device was individually calibrated to patients from the active group. Patients from the control group received an identical foot-worn platform without the biomechanical elements. Primary outcomes were the WOMAC Index and ALF assessments.</p> <p>Results</p> <p>There were no baseline differences between the groups. At 8 weeks, the active group showed a mean improvement of 64.8% on the WOMAC pain scale, a mean improvement of 62.7% on the WOMAC function scale, and a mean improvement of 31.4% on the ALF scale. The control group demonstrated no improvement in the above parameters. Significant differences were found between the active and control groups in all the parameters of assessment.</p> <p>Conclusions</p> <p>The biomechanical device and treatment methodology is effective in significantly reducing pain and improving function in knee OA patients.</p> <p>The study is registered at clinicaltrials.gov, identifier NCT00457132, <url>http://www.clinicaltrials.gov/ct/show/NCT00457132?order=1</url></p
Development of a perioperative medicine research agenda: a cross sectional survey
BACKGROUND: Post-operative complications are a significant source of morbidity and mortality for patients undergoing surgery. However, there is little research in the emerging field of perioperative medicine beyond cardiac risk stratification. We sought to determine the research priorities for perioperative medicine using a cross sectional survey of Canadian and American general internists. METHODS: Surveys were electronically sent to 312 general internists from the Canadian Society of Internal Medicine and 130 internists from the perioperative medicine research interest group within the US based Society of General Internal Medicine. The questionnaire contained thirty research questions and respondents were asked to rate the priority of these questions for future study. RESULTS: The research topics with the highest ratings included: the need for tight control of diabetes mellitus postoperatively and the value of starting aspirin on patients at increased risk for postoperative cardiac events. Research questions evaluating the efficacy and safety of perioperative interventions had higher ratings than questions relating to the prediction of postoperative risk. Questions relating to the yield of preoperative diagnostic tests had the lowest ratings (p < 0.001 for differences across these categories). CONCLUSION: The results of this survey suggest that practicing general internists believe that interventions studies are a priority within perioperative medicine. These findings should help prioritize research in this emerging field
Quantum Fluctuations and the Unruh Effect in Strongly-Coupled Conformal Field Theories
Through the AdS/CFT correspondence, we study a uniformly accelerated quark in
the vacuum of strongly-coupled conformal field theories in various dimensions,
and determine the resulting stochastic fluctuations of the quark trajectory.
From the perspective of an inertial observer, these are quantum fluctuations
induced by the gluonic radiation emitted by the accelerated quark. From the
point of view of the quark itself, they originate from the thermal medium
predicted by the Unruh effect. We scrutinize the relation between these two
descriptions in the gravity side of the correspondence, and show in particular
that upon transforming the conformal field theory from Rindler space to the
open Einstein universe, the acceleration horizon disappears from the boundary
theory but is preserved in the bulk. This transformation allows us to directly
connect our calculation of radiation-induced fluctuations in vacuum with the
analysis by de Boer et al. of the Brownian motion of a quark that is on average
static within a thermal medium. Combining this same bulk transformation with
previous results of Emparan, we are also able to compute the stress-energy
tensor of the Unruh thermal medium.Comment: 1+31 pages; v2: reference adde
Bioaccumulation of total mercury in the earthworm Eisenia andrei
Earthworms are a major part of the total biomass of soil fauna and play a vital role
in soil maintenance. They process large amounts of plant and soil material and can
accumulate many pollutants that may be present in the soil. Earthworms have been
explored as bioaccumulators for many heavy metal species such as Pb, Cu and Zn but
limited information is available for mercury uptake and bioaccumulation in earth-
worms and very few report on the factors that influence the kinetics of Hg uptake by
earthworms. It is known however that the uptake of Hg is strongly influenced by the
presence of organic matter, hence the influence of ligands are a major factor contribut
-
ing to the kinetics of mercury uptake in biosystems. In this work we have focused on
the uptake of mercury by earthworms (
Eisenia andrei
) in the presence of humic acid
(HA) under varying physical conditions of pH and temperature, done to assess the role
of humic acid in the bioaccumulation of mercury by earthworms from soils. The study
was conducted over a 5-day uptake period and all earthworm samples were analysed
by direct mercury analysis. Mercury distribution profiles as a function of time, bioac-
cumulation factors (BAFs), first order rate constants and body burden constants for
mercury uptake under selected conditions of temperature, pH as well as via the dermal
and gut route were evaluated in one comprehensive approach. The results showed
that the uptake of Hg was influenced by pH, temperature and the presence of HA.
Uptake of Hg
2
+
was improved at low pH and temperature when the earthworms in
soil were in contact with a saturating aqueous phase. The total amount of Hg
2
+
uptake
decreased from 75 to 48
% as a function of pH. For earthworms in dry soil, the uptake
was strongly influenced by the presence of the ligand. Calculated BAF values ranged
from 0.1 to 0.8. Mercury uptake typically followed first order kinetics with rate constants
determined as 0.2 to 1
h
?
1
.Scopus 201
Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.
The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation
- …