Structural and Energetic Mechanisms of Cooperative Autoinhibition and Activation of Vav1

SummaryVav proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases. They control processes including T cell activation, phagocytosis, and migration of normal and transformed cells. We report the structure and biophysical and cellular analyses of the five-domain autoinhibitory element of Vav1. The catalytic Dbl homology (DH) domain of Vav1 is controlled by two energetically coupled processes. The DH active site is directly, but weakly, inhibited by a helix from the adjacent Acidic domain. This core interaction is strengthened 10-fold by contacts of the calponin homology (CH) domain with the Acidic, pleckstrin homology, and DH domains. This construction enables efficient, stepwise relief of autoinhibition: initial phosphorylation events disrupt the modulatory CH contacts, facilitating phosphorylation of the inhibitory helix and consequent GEF activation. Our findings illustrate how the opposing requirements of strong suppression of activity and rapid kinetics of activation can be achieved in multidomain systems

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure MESA (Multi-Ethnic Study of Atherosclerosis)

ObjectivesThe objective of this study was to investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction.BackgroundThe association of resting heart rate to HF and LV function has not been well described in an asymptomatic multi-ethnic population.MethodsResting heart rate was measured in participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial at inclusion. Incident HF was registered (n = 176) during follow-up (median 7 years) in those who underwent cardiac magnetic resonance imaging (n = 5,000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1,056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume, and mass in addition to resting heart rate.ResultsCox analysis demonstrated that for 1 beat/min increase in resting heart rate, there was a 4% greater adjusted relative risk for incident HF (hazard ratio: 1.04; 95% CI: 1.02 to 1.06; p < 0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even when all coronary heart disease events were excluded from the model.ConclusionsElevated resting heart rate was associated with increased risk for incident HF in asymptomatic participants in the MESA trial. Higher heart rate was related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487

Teleparallel Version of the Levi-Civita Vacuum Solutions and their Energy Contents

In this paper, we find the teleparallel version of the Levi-Civita metric and obtain tetrad and the torsion fields. The tensor, vector and the axial-vector parts of the torsion tensor are evaluated. It is found that the vector part lies along the radial direction only while the axial-vector vanishes everywhere because the metric is diagonal. Further, we use the teleparallel version of M$\ddot{o}$ller, Einstein, Landau-Lifshitz and Bergmann-Thomson prescriptions to find the energy-momentum distribution of this metric and compare the results with those already found in General Relativity. It is worth mentioning here that momentum is constant in both the theories for all the prescriptions. The energy in teleparallel theory is equal to the corresponding energy in GR only in M$\ddot{o}$ller prescription for the remaining prescriptions, the energy do not agree in both theories. We also conclude that M$\ddot{o}$ller's energy-momentum distribution is independent of the coupling constant $\lambda$ in the teleparallel theory.Comment: 15 pages, accepted for publication in Canadian J. Physic

A New Computational Fluid Dynamics Code I: Fyris Alpha

A new hydrodynamics code aimed at astrophysical applications has been developed. The new code and algorithms are presented along with a comprehensive suite of test problems in one, two, and three dimensions. The new code is shown to be robust and accurate, equalling or improving upon a set of comparison codes. Fyris Alpha will be made freely available to the scientific community.Comment: 59 pages, 27 figures For associated code see http://www.mso.anu.edu.au/fyri

Cichlid biogeography: comment and review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72313/1/j.1467-2979.2004.00148.x.pd

The Physics of Star Cluster Formation and Evolution

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe