Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway

<p>Abstract</p> <p>Background</p> <p>Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of <it>Plasmodium falciparum </it>CK2 (PfCK2) are unknown. The parasite's genome encodes one catalytic subunit, PfCK2α, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2β1 and PfCK2β2.</p> <p>Results</p> <p>We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2β1 and PfCK2β2) cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA)-tagged catalytic and regulatory subunits (HA-CK2α, HA-PfCK2β1 or HA-PfCK2β2), and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2β1- and PfCK2β2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2β1 and PfCK2β2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps), histones, and two members of the Alba family are phosphorylated by PfCK2α <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites.</p

Hubble Space Telescope WFPC2 Imaging of SN 1979C and Its Environment

The locations of supernovae in the local stellar and gaseous environment in galaxies contain important clues to their progenitor stars. As part of a program to study the environments of supernovae using Hubble Space Telescope (HST) imaging data, we have examined the environment of the Type II-L SN 1979C in NGC 4321 (M100). We place more rigorous constraints on the mass of the SN progenitor, which may have had a mass M \approx 17--18 M_sun. Moreover, we have recovered and measured the brightness of SN 1979C, m=23.37 in F439W (~B; m_B(max) = 11.6), 17 years after explosion. .Comment: 18 pages, 8 figures, submitted to PAS

P-Type Silicon Strip Sensors for the new CMS Tracker at HL-LHC

The upgrade of the LHC to the High-Luminosity LHC (HL-LHC) is expected to increase the LHC design luminosity by an order of magnitude. This will require silicon tracking detectors with a significantly higher radiation hardness. The CMS Tracker Collaboration has conducted an irradiation and measurement campaign to identify suitable silicon sensor materials and strip designs for the future outer tracker at the CMS experiment. Based on these results, the collaboration has chosen to use n-in-p type silicon sensors and focus further investigations on the optimization of that sensor type. This paper describes the main measurement results and conclusions that motivated this decision

Spatially self-similar locally rotationally symmetric perfect fluid models

Einstein's field equations for spatially self-similar locally rotationally symmetric perfect fluid models are investigated. The field equations are rewritten as a first order system of autonomous ordinary differential equations. Dimensionless variables are chosen in such a way that the number of equations in the coupled system of differential equations is reduced as far as possible. The system is subsequently analyzed qualitatively for some of the models. The nature of the singularities occurring in the models is discussed.Comment: 27 pages, pictures available at ftp://vanosf.physto.se/pub/figures/ssslrs.tar.g

The thermal and two-particle stress-energy must be ill-defined on the 2-d Misner space chronology horizon

We show that an analogue of the (four dimensional) image sum method can be used to reproduce the results, due to Krasnikov, that for the model of a real massless scalar field on the initial globally hyperbolic region IGH of two-dimensional Misner space there exist two-particle and thermal Hadamard states (built on the conformal vacuum) such that the (expectation value of the renormalised) stress-energy tensor in these states vanishes on IGH. However, we shall prove that the conclusions of a general theorem by Kay, Radzikowski and Wald still apply for these states. That is, in any of these states, for any point b on the Cauchy horizon and any neighbourhood N of b, there exists at least one pair of non-null related points (x,x'), with x and x' in the intersection of IGH with N, such that (a suitably differentiated form of) its two-point function is singular. (We prove this by showing that the two-point functions of these states share the same singularities as the conformal vacuum on which they are built.) In other words, the stress-energy tensor in any of these states is necessarily ill-defined on the Cauchy horizon.Comment: 6 pages, LaTeX, RevTeX, no figure

Segond's fracture: a biomechanical cadaveric study using navigation

Background Segond’s fracture is a well-recognised radiological sign of an anterior cruciate ligament (ACL) tear. While previous studies evaluated the role of the anterolateral ligament (ALL) and complex injuries on rotational stability of the knee, there are no studies on the biomechanical effect of Segond’s fracture in an ACL deficient knee. The aim of this study was to evaluate the effect of a Segond’s fracture on knee rotation stability as evaluated by a navigation system in an ACL deficient knee. Materials and methods Three different conditions were tested on seven knee specimens: intact knee, ACL deficient knee and ACL deficient knee with Segond’s fracture. Static and dynamic measurements of anterior tibial translation (ATT) and axial tibial rotation (ATR) were recorded by the navigation system (2.2 OrthoPilot ACL navigation system B. Braun Aesculap, Tuttlingen, Germany). Results Static measurements at 30 showed that the mean ATT at 30 of knee flexion was 5.1 ± 2.7 mm in the ACL intact condition, 14.3 ± 3.1 mm after ACL cut (P = 0.005), and 15.2 ± 3.6 mm after Segond’s fracture (P = 0.08). The mean ATR at 30 of knee flexion was 20.7 ± 4.8 in the ACL intact condition, 26.9 ± 4.1 in the ACL deficient knee (P[0.05) and 30.9 ± 3.8 after Segond’s fracture (P = 0.005). Dynamic measurements during the pivot-shift showed that the mean ATT was 7.2 ± 2.7 mm in the intact knee, 9.1 ± 3.3 mm in the ACL deficient knee(P = 0.04) and 9.7 ± 4.3 mm in the ACL deficient knee with Segond’s fracture (P = 0.07). The mean ATR was 9.6 ± 1.8 in the intact knee, 12.3 ± 2.3 in the ACL deficient knee (P[0.05) and 19.1 ± 3.1 in the ACL deficient knee with Segond’s lesion (P = 0.016). Conclusion An isolated lesion of the ACL only affects ATT during static and dynamic measurements, while the addition of Segond’s fracture has a significant effect on ATR in both static and dynamic execution of the pivot-shift test, as evaluated with the aid of navigation

Integrability of irrotational silent cosmological models

We revisit the issue of integrability conditions for the irrotational silent cosmological models. We formulate the problem both in 1+3 covariant and 1+3 orthonormal frame notation, and show there exists a series of constraint equations that need to be satisfied. These conditions hold identically for FLRW-linearised silent models, but not in the general exact non-linear case. Thus there is a linearisation instability, and it is highly unlikely that there is a large class of silent models. We conjecture that there are no spatially inhomogeneous solutions with Weyl curvature of Petrov type I, and indicate further issues that await clarification.Comment: Minor corrections and improvements; 1 new reference; to appear Class. Quantum Grav.; 16 pages Ioplpp

A new proof of the Bianchi type IX attractor theorem

We consider the dynamics towards the initial singularity of Bianchi type IX vacuum and orthogonal perfect fluid models with a linear equation of state. The `Bianchi type IX attractor theorem' states that the past asymptotic behavior of generic type IX solutions is governed by Bianchi type I and II vacuum states (Mixmaster attractor). We give a comparatively short and self-contained new proof of this theorem. The proof we give is interesting in itself, but more importantly it illustrates and emphasizes that type IX is special, and to some extent misleading when one considers the broader context of generic models without symmetries.Comment: 26 pages, 5 figure

Spatially self-similar spherically symmetric perfect-fluid models

Einstein's field equations for spatially self-similar spherically symmetric perfect-fluid models are investigated. The field equations are rewritten as a first-order system of autonomous differential equations. Dimensionless variables are chosen in such a way that the number of equations in the coupled system is reduced as far as possible and so that the reduced phase space becomes compact and regular. The system is subsequently analysed qualitatively with the theory of dynamical systems.Comment: 21 pages, 6 eps-figure

Monotonic functions in Bianchi models: Why they exist and how to find them

All rigorous and detailed dynamical results in Bianchi cosmology rest upon the existence of a hierarchical structure of conserved quantities and monotonic functions. In this paper we uncover the underlying general mechanism and derive this hierarchical structure from the scale-automorphism group for an illustrative example, vacuum and diagonal class A perfect fluid models. First, kinematically, the scale-automorphism group leads to a reduced dynamical system that consists of a hierarchy of scale-automorphism invariant sets. Second, we show that, dynamically, the scale-automorphism group results in scale-automorphism invariant monotone functions and conserved quantities that restrict the flow of the reduced dynamical system.Comment: 26 pages, replaced to match published versio