Mol. Cell. Proteomics

Chemical cross-linking in combination with mass spectrometric analysis offers the potential to obtain low-resolution structural information from proteins and protein complexes. Identification of peptides connected by a cross-link provides direct evidence for the physical interaction of amino acid side chains, information that can be used for computational modeling purposes. Despite impressive advances that were made in recent years, the number of experimentally observed cross-links still falls below the number of possible contacts of cross-linkable side chains within the span of the cross-linker. Here, we propose two complementary experimental strategies to expand cross-linking data sets. First, enrichment of cross-linked peptides by size exclusion chromatography selects cross-linked peptides based on their higher molecular mass, thereby depleting the majority of unmodified peptides present in proteolytic digests of cross-linked samples. Second, we demonstrate that the use of proteases in addition to trypsin, such as Asp-N, can additionally boost the number of observable cross-linking sites. The benefits of both SEC enrichment and multiprotease digests are demonstrated on a set of model proteins and the improved workflow is applied to the characterization of the 20S proteasome from rabbit and Schizosaccharomyces pombe

Can We Study Titin Properties in Passive Myofibrils?

Titin is a giant molecular spring in skeletal and cardiac muscles. It has a variety of important passive, structural, sensing and force-regulatory functions, and thus has been investigated widely (Granzier & Labeit, 2007). Studying the mechanical properties of isolated titin has been difficult because of the enormous size and great instability of this protein. However, the passive properties in single myofibrils are almost exclusively explained by titin, and thus we asked the question if we can study titin properties in intact, passive myofibrils (Bartoo et al., 1997). Single myofibrils were isolated in a standard way (Leonard & Herzog, 2010) and three consecutive stretches of 1.0-3.5μm/sarcomere magnitude were performed at a nominal stretch speed of 0.1 sarcomere length/sarcomere/s. Sarcomere length were measured using a high resolution photo diode array and forces were measured using micro-electronically machined silicon nitrate levers. Single myofibrils frequently showed a distinct change in stiffness upon stretch at sarcomere length of approximately 3.6-3.8μm, they showed a decrease in loading energy with repeat stretch cycles and their efficiency decreased for all loading cycles with increasing stretch magnitude. These properties are in agreement with results observed in single titin preparations (Kellermayer et al., 1997). Therefore, we conclude that titin properties can be studied using single myofibrils. This has at least two significant advantages over tests with isolated titin proteins: (i) testing is technically much easier and (ii) titin is arranged in its intact structural arrangement. In the future, we would like to study titin properties in calcium activated myofibrils in which active (actin-myosin based cross-bridges forces) are eliminated either by chemical inhibition or by deletion of regulatory proteins on actin, as we have done before (Joumaa et al., 2008)

Critical dynamics in spontaneous resting-state oscillations are associated with the attention-related P300 ERP in a go/nogo task

Sustained attention is the ability to continually concentrate on task-relevant information, even in the presence of distraction. Understanding the neural mechanisms underlying this ability is critical for comprehending attentional processes as well as neuropsychiatric disorders characterized by attentional deficits, such as attention deficit hyperactivity disorder (ADHD). In this study, we aimed to investigate how trait-like critical oscillations during rest relate to the P300 evoked potential-a biomarker commonly used to assess attentional deficits. We measured long-range temporal correlations (LRTC) in resting-state EEG oscillations as index for criticality of the signal. In addition, the attentional performance of the subjects was assessed as reaction time variability (RTV) in a continuous performance task following an oddball paradigm. P300 amplitude and latencies were obtained from EEG recordings during this task. We found that, after controlling for individual variability in task performance, LRTC were positively associated with P300 amplitudes but not latencies. In line with previous findings, good performance in the sustained attention task was related to higher P300 amplitudes and earlier peak latencies. Unexpectedly, we observed a positive relationship between LRTC in ongoing oscillations during rest and RTV, indicating that greater criticality in brain oscillations during rest relates to worse task performance. In summary, our results show that resting-state neuronal activity, which operates near a critical state, relates to the generation of higher P300 amplitudes. Brain dynamics close to criticality potentially foster a computationally advantageous state which promotes the ability to generate higher event-related potential (ERP) amplitudes

Compositional Performance Modelling with the TIPPtool

Stochastic process algebras have been proposed as compositional specification formalisms for performance models. In this paper, we describe a tool which aims at realising all beneficial aspects of compositional performance modelling, the TIPPtool. It incorporates methods for compositional specification as well as solution, based on state-of-the-art techniques, and wrapped in a user-friendly graphical front end. Apart from highlighting the general benefits of the tool, we also discuss some lessons learned during development and application of the TIPPtool. A non-trivial model of a real life communication system serves as a case study to illustrate benefits and limitations

Theory and Phenomenology of Heavy Flavor at RHIC

We review the problem of heavy-quark diffusion in the Quark-Gluon Plasma and its ramifications for heavy-quark spectra in heavy-ion collisions at RHIC. In particular, we attempt to reconcile underlying mechanisms of several seemingly different approaches that have been put forward to explain the large suppression and elliptic flow of non-photonic electron spectra. We also emphasize the importance of a quantitative description of the bulk medium evolution to extract reliable values for the heavy-quark diffusion coefficient.Comment: 8 pages latex, including 10 eps figures; plenary talk at SQM08, Beijing (China), Oct. 06-10, 200

p-Wave holographic superconductors with Weyl corrections

We study the (3+1) dimensional p-wave holographic superconductors with Weyl corrections both numerically and analytically. We describe numerically the behavior of critical temperature $T_{c}$ with respect to charge density $\rho$ in a limited range of Weyl coupling parameter $\gamma$ and we find in general the condensation becomes harder with the increase of parameter $\gamma$. In strong coupling limit of Yang-Mills theory, we show that the minimum value of $T_{c}$ obtained from analytical approach is in good agreement with the numerical results, and finally show how we got remarkably a similar result in the critical exponent 1/2 of the chemical potential $\mu$ and the order parameter$$ with the numerical curves of superconductors.Comment: 7 pages, 1 figure, 1 table. One refrence added, presentations improve

Long-term periarticular bone adaptation in a feline knee injury model for post-traumatic experimental osteoarthritis

SummaryObjectivesThis study investigates the long-term changes of the periarticular bone, including cancellous bone and the subchondral plate, in an anterior cruciate ligament (ACL)-transected cat for post-traumatic osteoarthritis (OA). These periarticular bone changes are related to the health of all knee tissues including articular cartilage degeneration and may be a key component of osteoarthritic development.MethodsThirteen cats (mean mass 4.9±1.9kg) were divided into three experimental groups: (1) normal controls, (2) 16 week, and (3) 5 year post unilateral ACL-transection (ACLT). Micro-computed tomography was used to scan the three-dimensional (3D) bone architecture of the proximal tibia, and analysis was performed on the subchondral plate and cancellous bone in the epiphyseal and metaphyseal regions of each bone.ResultsA decrease in cancellous bone mass (BV/TV) and subchondral plate thickness (Ct.Th) was observed 16 week post-ACLT, and the trend was statistically significant for the long-term animals (>5 year post-ACLT: BV/TV decreased 16.8%, P<0.003; Ct.Th decreased 36.8%, P<0.03). A decrease in bone mass was also observed as a function of animal age by comparing the young and aged normal control animals, however ACLT intensified those changes, particularly Ct.Th (P<0.009) and anisotropy (P<0.045). It was speculated that decreased internal joint loading despite normal kinematics may play an important role in the long-term reduction of cancellous bone volume and subchondral plate thinning.ConclusionsThe periarticular bone changes measured in this study were concurrent with articular cartilage degeneration, and suggest that bone may be a contributing factor in the aetiology of post-traumatic OA development

Surprising Connections Between General Relativity and Condensed Matter

This brief review is intended to introduce gravitational physicists to recent developments in which general relativity is being used to describe certain aspects of condensed matter systems, e.g., superconductivity.Comment: 14 pages; based on talk given at GR1

The 10Be contents of SNC meteorites

Several authors have explored the possibility that the Shergottites, Nakhlites, and Chassigny (SNC) came from Mars. The spallogenic gas contents of the SNC meteorites have been used to: constrain the sizes of the SNC's during the last few million years; to establish groupings independent of the geochemical ones; and to estimate the likelihood of certain entries in the catalog of all conceivable passages from Mars to Earth. The particular shielding dependence of Be-10 makes the isotope a good probe of the irradiation conditions experienced by the SNC meteorites. The Be-10 contents of nine members of the group were measured using the technique of accelerator mass spectrometry. The Be-10 contents of Nakhla, Governador Valadares, Chassigny, and probably Lafayette, about 20 dpm/kg, exceed the values expected from irradiation of the surface of a large body. The Be-10 data therfore do not support scenario III of Bogard et al., one in which most of the Be-10 in the SNC meteorites would have formed on the Martian surface; they resemble rather the Be-10 contents found in many ordinary chondrites subjected to 4 Pi exposures. The uncertainties of the Be-10 contents lead to appreciable errors in the Be-10 ages, t(1) = -1/lambda ln(1 Be-10/Be-10). Nonetheless, the Be-10 ages are consistent with the Ne-21 ages calculated assuming conventional, small-body production rates and short terrestrial ages for the finds. It is believed that this concordance strengthens the case for at least 3 different irradiation ages for the SNC meteorites. Given the similar half-thicknesses of the Be-10 and Ne-21 production rates, the ratios of the Be-10 and Ne-21 contents do not appear consistent with common ages for any of the groups. In view of the general agreement between the Be-10 and Ne-21 ages it does not seem useful at this time to construct multiple-stage irradiation histories for the SNC meteorites