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

Multiplet Effects in the Quasiparticle Band Structure of the f1−f2f^1-f^2 Anderson Model

In this paper, we examine the mean field electronic structure of the $f^1-f^2$ Anderson lattice model in a slave boson approximation, which should be useful in understanding the physics of correlated metals with more than one f electron per site such as uranium-based heavy fermion superconductors. We find that the multiplet structure of the $f^2$ ion acts to quench the crystal field splitting in the quasiparticle electronic structure. This is consistent with experimental observations in such metals as $UPt_3$.Comment: 9 pages, revtex, 3 uuencoded postscript figures attached at en

Weak Field Magnetoresistance in Quasi-One-Dimensional Systems

Theoretical studies are presented on weak localization effects and magnetoresistance in quasi-one-dimensional systems with open Fermi surfaces. Based on the Wigner representation, the magnetoresistance in the region of weak field has been studied for five possible configurations of current and field with respect to the one-dimensional axis. It has been indicated that the anisotropy and its temperature dependences of the magnetoresistance will give information on the degree of one-dimensionality and the phase relaxation time.Comment: pages 11, LaTeX, 5 figures, uses jpsj.sty. To be published in J. Phys. Soc. Jpn. (Vol.67(1998) No.4); Added some references and a Note at Feb. 13 199

The complexity of selection at the major primate β-defensin locus

BACKGROUND: We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. RESULTS: We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. CONCLUSIONS: Identification of these putatively functional sites has important implications for our understanding of β-defensin function and for novel antibiotic design

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring \u3e1 year after whole-breast irradiation, \u3c3 \u3ecm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 \u3e1 to ≤2 cm, and 1 \u3e2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare

Plasma Resonance in Layered Normal Metals and Superconductors

A microscopic theory of the plasma resonance in layered metals is presented. It is shown that electron-impurity scattering can suppress the plasma resonance in the normal state and sharpen it in the superconducting state. Analytic properties of the conductivity for the electronic transport perpendicular to the layers are investigated. The dissipative part of the electromagnetic response in c-direction has been found to depend on frequency in a highly non-trivial manner. This sort of behavior cannot be incorporated in the widely used phenomenological Gorter-Kazimir model.Comment: 34 pages including 12 figures in uuencoded.file. A revised version. Several formulas and a number of misprints are corrected. A problem with printing of figures is fixe

First order transition from correlated electron semiconductor to ferromagnetic metal in single crystalline FeSi1-xGex

The phase diagram of FeSi1-xGex, obtained from magnetic, thermal and transport measurements on single crystals, shows a first-order transition from a correlated electron semiconductor to a ferromagnetic metal at a critical concentration, x ~ 0.25. The gap of the insulating phase strongly decreases with x. The specific heat coefficient appears to track the density of states of a Kondo insulator. The phase diagram is consistent with a correlation induced insulator-metal transition in conjunction with disorder on the Si/Ge ligand site

Slave-Boson Mean-Field Theory of the Antiferromagnetic State in the Doubly Degenerate Hubbard Model - the Half-Filled Case -

The antiferromagnetic ground state of the half-filled Hubbard model with the doubly degenerate orbital has been studied by using the slave-boson mean-field theory which was previously proposed by the present author. Numerical calculations for the simple cubic model have shown that the metal-insulator transition does not take place except at the vanishing interaction point, in strong contrast with its paramagnetic solution. The energy gap in the density of states of the antiferromagnetic insulator is much reduced by the effect of electron correlation. The exchange interaction $J$ plays an important role in the antiferromagnetism: although for $J = 0$ the sublattice magnetic moment $m$ in our theory is fairly smaller than $m_{HFA}$ obtained in the Hartree-Fock approximation, $m$ for $J/U > 0.2$ ($U$: the Coulomb interaction) is increased to become comparable to $m_{HFA}$. Surprisingly, the antiferromagnetic state is easily destroyed if a small, negative exchange interaction ($J/U < -0.05$) is introduced.Comment: Latex 18 pages, 12 figures available on request to [email protected] Note: published in Phys. Rev. B with some minor modification