1,164 research outputs found
Combined Application of Orthogonal Sortases and Depsipeptide Substrates for Dual Protein Labeling
Staphylococcus aureus sortase A is a transpeptidase that has been extensively exploited for site-specific modification of proteins and was originally used to attach a labeling reagent containing an LPXTG recognition sequence to a protein or peptide with an N-terminal glycine. Sortase mutants with other recognition sequences have also been reported, but in all cases, the reversibility of the transpeptidation reaction limits the efficiency of sortase-mediated labeling reactions. For the wildtype sortase, depsipeptide substrates, in which the scissile peptide bond is replaced with an ester, allow effectively irreversible sortase-mediated labeling as the alcohol byproduct is a poor competing nucleophile. In this paper, the use of depsipeptide substrates for evolved sortase variants is reported. Substrate specificities of three sortases have been investigated allowing identification of an orthogonal pair of enzymes accepting LPEToG and LPESoG depsipeptides, which have been applied to dual N-terminal labeling of a model protein mutant containing a second, latent N-terminal glycine residue. The method provides an efficient orthogonal site-specific labeling technique that further expands the biochemical protein labeling toolkit
Atomic transition frequencies, isotope shifts, and sensitivity to variation of the fine structure constant for studies of quasar absorption spectra
Theories unifying gravity with other interactions suggest spatial and
temporal variation of fundamental "constants" in the Universe. A change in the
fine structure constant, alpha, could be detected via shifts in the frequencies
of atomic transitions in quasar absorption systems. Recent studies using 140
absorption systems from the Keck telescope and 153 from the Very Large
Telescope, suggest that alpha varies spatially. That is, in one direction on
the sky alpha seems to have been smaller at the time of absorption, while in
the opposite direction it seems to have been larger.
To continue this study we need accurate laboratory measurements of atomic
transition frequencies. The aim of this paper is to provide a compilation of
transitions of importance to the search for alpha variation. They are E1
transitions to the ground state in several different atoms and ions, with
wavelengths ranging from around 900 - 6000 A, and require an accuracy of better
than 10^{-4} A. We discuss isotope shift measurements that are needed in order
to resolve systematic effects in the study. The coefficients of sensitivity to
alpha-variation (q) are also presented.Comment: Includes updated version of the "alpha line" lis
Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland
Factor H autoantibodies can impair complement
regulation, resulting in atypical hemolytic uremic
syndrome, predominantly in childhood. There are no trials
investigating treatment, and clinical practice is only
informed by retrospective cohort analysis. Here we
examined 175 children presenting with atypical hemolytic
uremic syndrome in the United Kingdom and Ireland for
factor H autoantibodies that included 17 children with
titers above the international standard. Of the 17, seven
had a concomitant rare genetic variant in a gene encoding
a complement pathway component or regulator. Two
children received supportive treatment; both developed
established renal failure. Plasma exchange was associated
with a poor rate of renal recovery in seven of 11 treated. Six
patients treated with eculizumab recovered renal function.
Contrary to global practice, immunosuppressive therapy to
prevent relapse in plasma exchangeâtreated patients was
not adopted due to concerns over treatment-associated
complications. Without immunosuppression, the relapse
rate was high (five of seven). However, reintroduction of
treatment resulted in recovery of renal function. All
patients treated with eculizumab achieved sustained
remission. Five patients received renal transplants without
specific factor H autoantibodyâtargeted treatment with
recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate
eculizumab therapy for treatment of factor H
autoantibodyâmediated atypical hemolytic uremic
syndrome rather than plasma exchange with or without
immunosuppression. Based on this retrospective analysis
we see no suggestion of inferior treatment, albeit the
strength of our conclusions is limited by the small sample siz
The XMM-Newton serendipitous survey - II. First results from the AXIS high galactic latitude medium sensitivity survey
We present the first results on the identifications of a medium sensitivity survey (X-ray flux limit 2 x 10(-14) erg cm(-2) s(-1) in the 0.5-4.5 keV band) at high galactic latitude (\b\ > 20degrees) carried out with the XMM-Newton X-ray observatory within the AXIS observing programme. This study is being conducted as part of the XMM-Newton Survey Science Centre activities towards the identification of the sources in the X-ray serendipitous sky survey. The sample contains 29 X-ray sources in a solid angle of 0.26 deg(2) (source density 113 +/- 21 sources deg(-2)), out of which 27 (93%) have been identified. The majority of the sources are broad-line AGN (19), followed by narrow emission line X-ray emitting galaxies (6, all of which turn out to be AGN), 1 nearby non-emission line galaxy (NGC 4291) and 1 active coronal star. Among the identified sources we find 2 broad-absorption line QSOs (z similar to 1.8 and z similar to 1.9), which constitute similar to10% of the AGN population at this flux level, similar to optically selected samples. Identifications of a further 10 X-ray sources fainter than our survey limit are also presented
Using new technologies to promote weight management: a randomised controlled trial study protocol
Background: Over the last three decades, overweight and obesity and the associated health consequences have become global public health priorities. Methods that have been tried to address this problem have not had the desired impact, suggesting that other approaches need to be considered. One of the lessons learned throughout these attempts is that permanent weight loss requires sustained dietary and lifestyle changes, yet adherence to weight management programs has often been noted as one of the biggest challenges. This trial aims to address this issue by examining whether social media, as a potential health promotion tool, will improve adherence to a weight management program. To test the effectiveness of this measure, the designated program will be delivered via the popular social networking site Facebook, and compared to a standard delivery method that provides exactly the same content but which is communicated through a pamphlet. The trial will be conducted over a period of twelve weeks, with a twelve week follow-up. Although weight loss is expected, this study will specifically investigate the effectiveness of social media as a program delivery method. The program utilised will be one that has already been proven to achieve weight loss, namely The CSIRO Total Wellbeing Diet.Methods/design: This project will be conducted as a 3-arm randomised controlled trial. One hundred and twenty participants will be recruited from the Perth community, and will be randomly assigned to one of the following three groups: the Facebook group, the pamphlet group, or a control group. The Facebook Group will receive the weight management program delivered via a closed group in Facebook, the Pamphlet Group will be given the same weight management program presented in a booklet, and the Control Group will follow the Australian Dietary Guidelines and the National Physical Activity Guidelines for Adults as usual care. Change in weight, body composition and waist circumference will be initial indicators of adherence to the program. Secondary outcome measures will be blood glucose, insulin, blood pressure, arterial stiffness, physical activity, eating behaviour, mental well-being (stress, anxiety, and depression), social support, self-control, self-efficacy, Facebook activity, and program evaluation. Discussion: It is expected that this trial will support the use of social media - a source of social support and information sharing - as a delivery method for weight management programs, enhancing the reduction in weight expected from dietary and physical activity changes. Facebook is a popular, easy to access and cost-effective online platform that can be used to assist the formation of social groups, and could be translated into health promotion practice relatively easily. It is anticipated in the context of the predicted findings that social media will provide an invaluable resource for health professionals and patients alike
An Intermediate-mass Black Hole of Over 500 Solar Masses in the Galaxy ESO 243-49
Ultra-luminous X-ray sources are extragalactic objects located outside the
nucleus of the host galaxy with bolometric luminosities >10^39 erg s^-1. These
extreme luminosities - if the emission is isotropic and below the theoretical
(i.e. Eddington) limit, where the radiation pressure is balanced by the
gravitational pressure - imply the presence of an accreting black hole with a
mass of ~10^2-10^5 times that of the Sun. The existence of such intermediate
mass black holes is in dispute, and though many candidates have been proposed,
none are widely accepted as definitive. Here we report the detection of a
variable X-ray source with a maximum 0.2-10 keV luminosity of up to 1.2 x 10^42
erg s^-1 in the edge-on spiral galaxy ESO 243-49, with an implied conservative
lower limit of the mass of the black hole of ~500 Msun. This finding presents
the strongest observational evidence to date for the existence of intermediate
mass black holes, providing the long sought after missing link between the
stellar mass and super-massive black hole populations.Comment: 5 pages, 2 figures, 1 table, published in Natur
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at â s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fbâ1 of â s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at âs = 7 TeV with the ATLAS detector
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of âs = 7 TeV;{\rm Te}{\rm V}4.6\;{\rm f}{{{\rm b}}^{-1}}{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}|\eta |\lt 1.9{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at âs=8TeV
The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fbâ1of data collected in protonâproton collisions at âs=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV
Airway Microbiota and Pathogen Abundance in Age-Stratified Cystic Fibrosis Patients
Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective âearlyâ and âlateâ colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations
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