421 research outputs found
Single-molecule study of redox control involved in establishing the spinach plastocyanin-cytochrome b6f electron transfer complex
Small diffusible redox proteins play a ubiquitous role in bioenergetic systems, facilitating electron transfer (ET) between membrane bound complexes. Sustaining high ET turnover rates requires that the association between extrinsic and membrane-bound partners is highly specific, yet also sufficiently weak to promote rapid post-ET separation. In oxygenic photosynthesis the small soluble electron carrier protein plastocyanin (Pc) shuttles electrons between the membrane integral cytochrome b6f (cytb6f) and photosystem I (PSI) complexes. Here we use peak-force quantitative nanomechanical mapping (PF-QNM) atomic force microscopy (AFM) to quantify the dynamic forces involved in transient interactions between cognate ET partners. An AFM probe functionalised with Pc molecules is brought into contact with cytb6f complexes, immobilised on a planar silicon surface. PF-QNM interrogates the unbinding force of the cytb6f-Pc interactions at the single molecule level with picoNewton force resolution and on a time scale comparable to the ET time in vivo (ca. 120 μs). Using this approach, we show that although the unbinding force remains unchanged the interaction frequency increases over five-fold when Pc and cytb6f are in opposite redox states, so complementary charges on the cytb6f and Pc cofactors likely contribute to the electrostatic forces that initiate formation of the ET complex. These results suggest that formation of the docking interface is under redox state control, which lowers the probability of unproductive encounters between Pc and cytb6f molecules in the same redox state, ensuring the efficiency and directionality of this central reaction in the ‘Z-scheme’ of photosynthetic ET
Ab initio many-body calculations on infinite carbon and boron-nitrogen chains
In this paper we report first-principles calculations on the ground-state
electronic structure of two infinite one-dimensional systems: (a) a chain of
carbon atoms and (b) a chain of alternating boron and nitrogen atoms. Meanfield
results were obtained using the restricted Hartree-Fock approach, while the
many-body effects were taken into account by second-order M{\o}ller-Plesset
perturbation theory and the coupled-cluster approach. The calculations were
performed using 6-31 basis sets, including the d-type polarization
functions. Both at the Hartree-Fock (HF) and the correlated levels we find that
the infinite carbon chain exhibits bond alternation with alternating single and
triple bonds, while the boron-nitrogen chain exhibits equidistant bonds. In
addition, we also performed density-functional-theory-based local density
approximation (LDA) calculations on the infinite carbon chain using the same
basis set. Our LDA results, in contradiction to our HF and correlated results,
predict a very small bond alternation. Based upon our LDA results for the
carbon chain, which are in agreement with an earlier LDA calculation
calculation [ E.J. Bylaska, J.H. Weare, and R. Kawai, Phys. Rev. B 58, R7488
(1998).], we conclude that the LDA significantly underestimates Peierls
distortion. This emphasizes that the inclusion of many-particle effects is very
important for the correct description of Peierls distortion in one-dimensional
systems.Comment: 3 figures (included). To appear in Phys. Rev.
Low-mass pre--main-sequence stars in the Magellanic Clouds
[Abridged] The stellar Initial Mass Function (IMF) suggests that sub-solar
stars form in very large numbers. Most attractive places for catching low-mass
star formation in the act are young stellar clusters and associations, still
(half-)embedded in star-forming regions. The low-mass stars in such regions are
still in their pre--main-sequence (PMS) evolutionary phase. The peculiar nature
of these objects and the contamination of their samples by the evolved
populations of the Galactic disk impose demanding observational techniques for
the detection of complete numbers of PMS stars in the Milky Way. The Magellanic
Clouds, the companion galaxies to our own, demonstrate an exceptional star
formation activity. The low extinction and stellar field contamination in
star-forming regions of these galaxies imply a more efficient detection of
low-mass PMS stars than in the Milky Way, but their distance from us make the
application of special detection techniques unfeasible. Nonetheless, imaging
with the Hubble Space Telescope yield the discovery of solar and sub-solar PMS
stars in the Magellanic Clouds from photometry alone. Unprecedented numbers of
such objects are identified as the low-mass stellar content of their
star-forming regions, changing completely our picture of young stellar systems
outside the Milky Way, and extending the extragalactic stellar IMF below the
persisting threshold of a few solar masses. This review presents the recent
developments in the investigation of PMS stars in the Magellanic Clouds, with
special focus on the limitations by single-epoch photometry that can only be
circumvented by the detailed study of the observable behavior of these stars in
the color-magnitude diagram. The achieved characterization of the low-mass PMS
stars in the Magellanic Clouds allowed thus a more comprehensive understanding
of the star formation process in our neighboring galaxies.Comment: Review paper, 26 pages (in LaTeX style for Springer journals), 4
figures. Accepted for publication in Space Science Review
An Analytical Assessment of NASA's N+1 Subsonic Fixed Wing Project Noise Goal
The Subsonic Fixed Wing Project of NASA's Fundamental Aeronautics Program has adopted a noise reduction goal for new, subsonic, single-aisle, civil aircraft expected to replace current 737 and A320 airplanes. These so-called 'N+1' aircraft - designated in NASA vernacular as such since they will follow the current, in-service, 'N' airplanes - are hoped to achieve certification noise goal levels of 32 cumulative EPNdB under current Stage 4 noise regulations. A notional, N+1, single-aisle, twinjet transport with ultrahigh bypass ratio turbofan engines is analyzed in this study using NASA software and methods. Several advanced noise-reduction technologies are analytically applied to the propulsion system and airframe. Certification noise levels are predicted and compared with the NASA goal
Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol
Abstract
Introduction Osteoarthritis (OA) is a highly prevalent and disabling condition with limited safe and effective treatment options. Intra-articular therapies are increasingly being used, however whether the effect of these agents is due to active treatment or placebo remains unclear. As the placebo response can be attributed to multiple factors, assessment of the placebo response using individual patient data (IPD) meta-analysis will give insight into the different modifiers of response to placebo. The aim of this IPD meta-analysis is to investigate the predictors of placebo response in intra-articular injection trials in OA. IPD meta-analysis is considered to be superior to conventional meta-analysis, as it combines multiple trial data, facilitates the standardisation of analyses across different studies and allows measuring derivation of the desired information.
Method and analysis A systematic literature search will be conducted for randomised clinical trials comparing corticosteroid and viscosupplementation/hyaluronic acid intra-articular injections with placebo for knee and hip OA. Pubmed (Medline), EMBASE, Web of Science, Cochrane Central and SCOPUS will be searched from inception to September 2018. Corresponding authors of the original trials will be contacted to obtain IPD. Risk of bias will be assessed using the Cochrane Collaboration’s tool. The primary outcome will be change in pain from baseline. Secondary outcomes will be change in function and patient’s global assessment. Potential predictors of placebo response assessed will include patient’s characteristics, pain mechanism characteristics, radiographic severity, pain severity, intervention characteristics and trial design characteristics. A multilevel logistic regression analyses will be applied. Results will be reported using the Preferred Reporting Items for Systematic review and Meta-Analysis -IPD guidelines.
Ethics and dissemination This study does not include identifiable data and ethical approval was obtained by the original investigators. Results of the IPD meta-analysis will be disseminated for publication in peer-reviewed journals and conference presentations
Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis
INTRODUCTION: Randomised clinical trials to date investigating the efficacy of bisphosphonates in knee osteoarthritis (OA) have found divergent results, with a recent meta-analysis finding no superiority of these drugs over placebo. Whether particular patient subgroups are more likely to benefit from this therapy than others is still unclear. We aim to investigate the effects of bisphosphonates compared with a control group (placebo, no treatment, another active treatment) on clinical and structural outcomes in specific knee OA subpopulations with possible distinct rates of subchondral bone turnover. METHODS AND ANALYSIS: Medline, Embase, Scopus, Web of Sciences and Cochrane Central Register of Controlled Trials will be searched from inception to February 2018. Randomised clinical trials will be eligible if they reported at least one potential treatment effect modifier at baseline: gender, menopausal status, age, body mass index, radiographic stage, knee pain severity, presence of bone marrow lesions, levels of biochemical markers of bone turnover (serum and/or urinary) and systemic bone mineral density status. Authors of original trials will be contacted to obtain individual patient data from each study. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary o
Multidimensional Conservation Laws: Overview, Problems, and Perspective
Some of recent important developments are overviewed, several longstanding
open problems are discussed, and a perspective is presented for the
mathematical theory of multidimensional conservation laws. Some basic features
and phenomena of multidimensional hyperbolic conservation laws are revealed,
and some samples of multidimensional systems/models and related important
problems are presented and analyzed with emphasis on the prototypes that have
been solved or may be expected to be solved rigorously at least for some cases.
In particular, multidimensional steady supersonic problems and transonic
problems, shock reflection-diffraction problems, and related effective
nonlinear approaches are analyzed. A theory of divergence-measure vector fields
and related analytical frameworks for the analysis of entropy solutions are
discussed.Comment: 43 pages, 3 figure
A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program
Background Height has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank. Methods and findings Analyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n = 222,300) and non-Hispanic Black (AA, n = 58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes. As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD. We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders. Conclusions We conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study
Structures of Rhodopseudomonas palustris RC-LH1 complexes with open or closed quinone channels
The reaction-center light-harvesting complex 1 (RC-LH1) is the core photosynthetic component in purple phototrophic bacteria. We present two cryo–electron microscopy structures of RC-LH1 complexes from Rhodopseudomonas palustris. A 2.65-Å resolution structure of the RC-LH114-W complex consists of an open 14-subunit LH1 ring surrounding the RC interrupted by protein-W, whereas the complex without protein-W at 2.80-Å resolution comprises an RC completely encircled by a closed, 16-subunit LH1 ring. Comparison of these structures provides insights into quinone dynamics within RC-LH1 complexes, including a previously unidentified conformational change upon quinone binding at the RC QB site, and the locations of accessory quinone binding sites that aid their delivery to the RC. The structurally unique protein-W prevents LH1 ring closure, creating a channel for accelerated quinone/quinol exchange
- …