Viral Mimicry of Cdc2/Cyclin-Dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress

The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser22). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser22 is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle

Compressibility systematics of calcite-type borates : An experimental and theoretical structural study on ABO3 (A = Al, Sc, Fe and In)

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry C , copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp4124259The structural properties of calcite-type orthoborates ABO(3) (A = Al, Fe, Sc, and In) have been investigated at high pressures up to 32 GPa. They were studied experimentally using synchrotron powder X-ray diffraction and theoretically by means of ab initio total-energy calculations. We found that the calcite-type structure remains stable up to the highest pressure explored in the four studied compounds. Experimental and calculated static geometries (unit-cell parameters and internal coordinates), bulk moduli, and their pressure derivatives are in good agreement. The compressibility along the c axis is roughly three times that along the a axis. Our data clearly indicate that the compressibility of borates is dominated by that of the [AO(6)] octahedral group and depends on the size of the trivalent A cations. An analysis of the relationship between isomorphic borates and carbonates is also presented, which points to the potentiality of considering borates as chemical analogues of the carbonate mineral family.This study was supported by the Spanish government MEC under Grant Nos.: MAT2010-21270-C04-01/03/04 and CTQ2009-14596-C02-01, by MALTA Consolider Ingenio 2010 Project (CSD2007-00045), by Generalitat Valenciana (GVA-ACOMP-2013-1012), and by the Vicerrectorado de Investigacion y Desarrollo of the Universidad Politecnica de Valencia (UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11). We thank ALBA and Diamond synchrotrons for providing beamtime for the XRD experiments. A.M. and P.R-H. acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster. J.A.S. and B.G.-D. acknowledge Juan de la Cierva fellowship and FPI programs for financial support. We are gratefully indebted to Dr. Capponi and Dr. Diehl for supplying us single crystals of AlBO3 and FeBO3, respectively.Santamaría Pérez, D.; Gomis Hilario, O.; Sans, JÁ.; Ortiz, HM.; Vegas, Á.; Errandonea, D.; Ruiz-Fuertes, J.... (2014). Compressibility systematics of calcite-type borates : An experimental and theoretical structural study on ABO3 (A = Al, Sc, Fe and In). Journal of Physical Chemistry C. 118(8):4354-4361. https://doi.org/10.1021/jp4124259S43544361118

Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya

Background: Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. Methodology/Principal findings: We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4?9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0?17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. Conclusions/Significance: Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources

The Mollusca inhabiting rice fields in northern Cameroon and their role as intermediate hosts for schistosomes

A systematic account is given of the freshwater gastropod and bivalve fauna of Ouro-Doukoudje, northern Cameroon, based on a survey conducted from July 2000 to June 2001 at 12 sites in rice fields spanning 800 ha. In total, 14 species were encountered, one of them (Burnupia sp.) being a first record for the area. Thirteen of the species are widely distributed in the Sahelo-Sudanese or Afrotropical regions. Bulinus senegalensis, Bulinus forskalii, Bulinus globosus, Biomphalaria pfeifferi and Lymnaea natalensis occurred throughout the study area and are potential intermediate hosts for schistosomes. Only Biomphalaria pfeifferi was found to be naturally infected with Schistosoma mansoni at nearly all sites in the rice fields. Infection rates were high and varied among sites (21.0–68.6%) and months (14.8–76.6%). Bulinus forskalii was scarce in, and Bulinus truncatus absent from, the study area. Our data are compared with published data for this area as well as for northern Cameroon.Keywords: Biomphalaria, Bulinus, Burnupia, Cameroon, population dynamic

Morphological studies on Bulinus sp. (Gastropoda: Planorbidae) from Nchout Monoun, Cameroon

Since 1990, diploid Bulinus sp. populations have been reported from many sites in the volcanic western Bamileke and Bamoun plateau in Cameroon; starch gel electrophoresis of enzymes and chromosome analyses have revealed a single band in hydroxybutyrate dehydrogenase (HBDH), isocitrate dehydrogenase (IDH), and a diploid chromosome number of 2n = 36. Several samples have been tentatively identified as B. natalensis (Küster, 1841) on the basis of observations on the shell and radula. The present study is a preliminary analysis of the characteristics of the shell and the radula of the snails from Nchout Monoun Crater Lake (Monoun Koumogoum) for adequate comparisons with the widely studied B.  natalensis/tropicus complex from East and South Africa. Comparison of the ratio of shell length to aperture length (L/AL), plotted against shell length (L) in a scatter diagram,  showed a 47% overlap between the dimensions of the Nchout Monoun sample and those from KwaZulu-Natal. From previous observations on the diploid chromosome number, single electrophoretic bands on HBDH and IDH enzyme  systems, euphallic genital system, arrowhead-shaped mesocones and the   characteristic features of the shell, we conclude that Bulinus sp. from Nchout  Monoun is closely related to B. natalensis.Key words: Bulinus, Cameroon, South Africa, shell morphology

Petrology of lherzolite xenoliths of Hosséré Sédé volcano (Adamawa plateau, Ngaoundéré area, Cameroon)

International audienceNumerous mantle xenoliths 6–12 cm in size and sub-angular to rounded in shape occur within Mio-Pliocene basanite lavas of the monogenic volcano of Hosséré Sédé in the Adamawa plateau. Xenoliths of spinel lherzolite exhibit protogranular, equigranular or porphyroclastic texture. Microprobe chemical analyses show that olivine is highly magnesian (Fo88-90), clinopyroxene crystals are diopside and augite (Wo41.6–49.6 En45.3–53.7 Fs4.2–6.2), orthopyroxene crystals are enstatite (Wo1.4–1.5 En88.6–89.0 Fs9.6–9.9) and spinel crystals are mainly Al-spinel associated to minor Cr-spinel. Estimated temperatures and pressures through empirical formulas show that Hosséré Sédé xenoliths have equilibrated between 1085 and 1204 °C and 1.08 to 1.57 GPa, corresponding to sampling depths of 36 and 52 km. Detailed petrographical and mineral chemistry of Hosséré Sédé xenoliths evidences the complex nature and composition of the subcontinental lithosphere under the Adamawa plateau. This may involve a probable uplift of the whole area after a limited extensional event, possible metasomatism through melt infiltration during shearing of the lithospheric mantle along the Pan African strike-slip fault system

Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo

E-type cyclins (cyclins E1 and E2) are components of the cell cycle machinery that has been conserved from yeast to humans. The major function of E-type cyclins is to drive cell division. It is unknown whether in addition to their ‘core’ cell cycle functions, E-type cyclins also perform unique tissue-specific roles. Here, we applied high-throughput mass spectrometric analyses of mouse organs to define the repertoire of cyclin E protein partners in vivo. We found that cyclin E interacts with distinct sets of proteins in different compartments. These cyclin E interactors are highly enriched for phosphorylation targets of cyclin E and its catalytic partner, the cyclin-dependent kinase 2 (Cdk2). Among cyclin E interactors we identified several novel tissue-specific substrates of cyclin E-Cdk2 kinase. In proliferating compartments, cyclin E-Cdk2 phosphorylates Lin proteins within the DREAM complex. In the testes, cyclin E-Cdk2 phosphorylates Mybl1 and Dmrtc2, two meiotic transcription factors that represent key regulators of spermatogenesis. In embryonic and adult brains cyclin E interacts with proteins involved in neurogenesis, while in adult brains also with proteins regulating microtubule-based processes and microtubule cytoskeleton. We also used quantitative proteomics to demonstrate re-wiring of the cyclin E interactome upon ablation of Cdk2. This approach can be used to study how protein interactome changes during development or in any pathological state such as aging or cancer

Quantitative proteomic (iTRAQ) analysis of cyclin E1-interacting proteins in mouse organs in the absence of Cdk2.

<p>(A) Relative abundance of cyclin E1-associated Cdk1, Cdk2, Cdk4, Cdk5 and p107 in the spleens of <i>Cdk2</i>^<i>-/-</i><i>/cyclin E1</i>^{<i>Ntag/Ntag</i>} mice, as compared to <i>Cdk2</i>^<i>+/+</i><i>/cyclin E1</i>^{<i>Ntag/Ntag</i>} animals, was determined by iTRAQ labeling and LC-MS. (B) The amount of cyclin E1-associated Cdk1, Cdk2, Cdk4, Cdk5 and p107 in the spleens of wild-type (Ctrl), <i>Cdk2</i>^<i>+/+</i><i>/cyclin E1</i>^{<i>Ntag/Ntag</i>} (KI), and <i>Cdk2</i>^<i>-/-</i><i>/cyclin E1</i>^{<i>Ntag/Ntag</i>} (Cdk2^<i>-/-</i>) mice was gauged by immunoprecipitation with an anti-Flag antibody and immunoblotting with the indicated antibodies. Abundance of each protein in total lysates (whole) is also shown. (C) Spleens from wild-type mice were incubated with 20 μM CVT-313 (+) or with vehicle only (-). Association of cyclin E1 with Cdk2, Cdk1, Cdk4 and Cdk5 was assessed by IP–western blotting. Whole, whole cell lysate from vehicle only-treated mice. Lower panel: To ensure that CVT-313 treatment inhibited Cdk2 kinase activity, Cdk2 was immunoprecipitated from lysates and used for <i>in vitro</i> kinase reactions with histone H1 as a substrate. Note that CVT-313 treatment strongly decreased Cdk2 kinase activity.</p