Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina

<p>Abstract</p> <p>Background</p> <p>The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC) and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described.</p> <p>Results</p> <p>Here, we report the positional cloning and detailed characterization of retinal phenotypes of a zebrafish mutation at the <it>cap-g </it>locus. High resolution live imaging reveals that the progression of mitosis between prometa- to telophase is delayed and that sister chromatid segregation is impaired upon loss of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic mislocalization of CAP-G throughout mitosis. DNA content analysis reveals increased genomic imbalances upon loss of non-SMC condensin I subunits. Within the retina, loss of condensin I function causes increased rates of apoptosis among cells within the proliferative ciliary marginal zone (CMZ) whereas postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis partially rescues cell numbers in <it>cap-g </it>mutant retinae and allows normal layering of retinal cell types without alleviating their aberrant nuclear sizes.</p> <p>Conclusion</p> <p>Our findings indicate that the condensin I complex is particularly important within rapidly amplifying progenitor cell populations to ensure faithful chromosome segregation. In contrast, differentiation of postmitotic retinal cells is not impaired upon polyploidization.</p

Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina.

BACKGROUND: The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC) and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described. RESULTS: Here, we report the positional cloning and detailed characterization of retinal phenotypes of a zebrafish mutation at the cap-g locus. High resolution live imaging reveals that the progression of mitosis between prometa- to telophase is delayed and that sister chromatid segregation is impaired upon loss of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic mislocalization of CAP-G throughout mitosis. DNA content analysis reveals increased genomic imbalances upon loss of non-SMC condensin I subunits. Within the retina, loss of condensin I function causes increased rates of apoptosis among cells within the proliferative ciliary marginal zone (CMZ) whereas postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis partially rescues cell numbers in cap-g mutant retinae and allows normal layering of retinal cell types without alleviating their aberrant nuclear sizes. CONCLUSION: Our findings indicate that the condensin I complex is particularly important within rapidly amplifying progenitor cell populations to ensure faithful chromosome segregation. In contrast, differentiation of postmitotic retinal cells is not impaired upon polyploidization.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Characterizing the transition from diffuse atomic to dense molecular clouds in the Magellanic clouds with [CII], [CI], and CO

We present and analyze deep Herschel/HIFI observations of the [CII] 158um, [CI] 609um, and [CI] 370um lines towards 54 lines-of-sight (LOS) in the Large and Small Magellanic clouds. These observations are used to determine the physical conditions of the line--emitting gas, which we use to study the transition from atomic to molecular gas and from C^+ to C^0 to CO in their low metallicity environments. We trace gas with molecular fractions in the range 0.1<f(H2)<1, between those in the diffuse H2 gas detected by UV absorption (f(H2)<0.2) and well shielded regions in which hydrogen is essentially completely molecular. The C^0 and CO column densities are only measurable in regions with molecular fractions f(H2)>0.45 in both the LMC and SMC. Ionized carbon is the dominant gas-phase form of this element that is associated with molecular gas, with C^0 and CO representing a small fraction, implying that most (89% in the LMC and 77% in the SMC) of the molecular gas in our sample is CO-dark H2. The mean X_CO conversion factors in our LMC and SMC sample are larger than the value typically found in the Milky Way. When applying a correction based on the filling factor of the CO emission, we find that the values of X_CO in the LMC and SMC are closer to that in the Milky Way. The observed [CII] intensity in our sample represents about 1% of the total far-infrared intensity from the LOSs observed in both Magellanic Clouds.Comment: 32 pages, 21 figures, Accepted to Ap

Massive Quiescent Cores in Orion. -- II. Core Mass Function

We have surveyed submillimeter continuum emission from relatively quiescent regions in the Orion molecular cloud to determine how the core mass function in a high mass star forming region compares to the stellar initial mass function. Such studies are important for understanding the evolution of cores to stars, and for comparison to formation processes in high and low mass star forming regions. We used the SHARC II camera on the Caltech Submillimeter Observatory telescope to obtain 350 \micron data having angular resolution of about 9 arcsec, which corresponds to 0.02 pc at the distance of Orion. Our analysis combining dust continuum and spectral line data defines a sample of 51 Orion molecular cores with masses ranging from 0.1 \Ms to 46 \Ms and a mean mass of 9.8 \Ms, which is one order of magnitude higher than the value found in typical low mass star forming regions, such as Taurus. The majority of these cores cannot be supported by thermal pressure or turbulence, and are probably supercritical.They are thus likely precursors of protostars. The core mass function for the Orion quiescent cores can be fitted by a power law with an index equal to -0.85$\pm$0.21. This is significantly flatter than the Salpeter initial mass function and is also flatter than the core mass function found in low and intermediate star forming regions. Thus, it is likely that environmental processes play a role in shaping the stellar IMF later in the evolution of dense cores and the formation of stars in such regions.Comment: 30 pages, 10 figures, accepted by Ap

An Alumni survey of the School of Social Work, Portland State University

The alumni survey conducted at Portland State University School of Social Work by second year students had two purposes. One purpose was to fulfill the research practicum requirements of a Masters of Social Work degree by providing experience in the area of applied survey research. The other was to provide a data base for future alumni research at the school

ROS Promote Epigenetic Remodeling and Cardiac Dysfunction in Offspring Following Maternal Engineered Nanomaterial (ENM) Exposure

Background: Nano-titanium dioxide (nano-TiO2) is amongst the most widely utilized engineered nanomaterials (ENMs). However, little is known regarding the consequences maternal ENM inhalation exposure has on growing progeny during gestation. ENM inhalation exposure has been reported to decrease mitochondrial bioenergetics and cardiac function, though the mechanisms responsible are poorly understood. Reactive oxygen species (ROS) are increased as a result of ENM inhalation exposure, but it is unclear whether they impact fetal reprogramming. The purpose of this study was to determine whether maternal ENM inhalation exposure influences progeny cardiac development and epigenomic remodeling. Results: Pregnant FVB dams were exposed to nano-TiO2 aerosols with a mass concentration of 12.09 ± 0.26 mg/m3 starting at gestational day five (GD 5), for 6 h over 6 non-consecutive days. Aerosol size distribution measurements indicated an aerodynamic count median diameter (CMD) of 156 nm with a geometric standard deviation (GSD) of 1.70. Echocardiographic imaging was used to assess cardiac function in maternal, fetal (GD 15), and young adult (11 weeks) animals. Electron transport chain (ETC) complex activities, mitochondrial size, complexity, and respiration were evaluated, along with 5-methylcytosine, Dnmt1 protein expression, and Hif1α activity. Cardiac functional analyses revealed a 43% increase in left ventricular mass and 25% decrease in cardiac output (fetal), with an 18% decrease in fractional shortening (young adult). In fetal pups, hydrogen peroxide (H2O2) levels were significantly increased (~ 10 fold) with a subsequent decrease in expression of the antioxidant enzyme, phospholipid hydroperoxide glutathione peroxidase (GPx4). ETC complex activity IV was decreased by 68 and 46% in fetal and young adult cardiac mitochondria, respectively. DNA methylation was significantly increased in fetal pups following exposure, along with increased Hif1α activity and Dnmt1 protein expression. Mitochondrial ultrastructure, including increased size, was observed at both fetal and young adult stages following maternal exposure. Conclusions: Maternal inhalation exposure to nano-TiO2 results in adverse effects on cardiac function that are associated with increased H2O2 levels and dysregulation of the Hif1α/Dnmt1 regulatory axis in fetal offspring. Our findings suggest a distinct interplay between ROS and epigenetic remodeling that leads to sustained cardiac contractile dysfunction in growing and young adult offspring following maternal ENM inhalation exposure

Ultrastructural Characterization of SARS Coronavirus

Severe acute respiratory syndrome (SARS) was first described during a 2002–2003 global outbreak of severe pneumonia associated with human deaths and person-to-person disease transmission. The etiologic agent was initially identified as a coronavirus by thin-section electron microscopic examination of a virus isolate. Virions were spherical, 78 nm in mean diameter, and composed of a helical nucleocapsid within an envelope with surface projections. Herein, we show that infection with the SARS-associated coronavirus resulted in distinct ultrastructural features: double-membrane vesicles, nucleocapsid inclusions, and large granular areas of cytoplasm. These three structures and the coronavirus particles were shown to be positive for viral proteins and RNA by using ultrastructural immunogold and in situ hybridization assays. In addition, ultrastructural examination of a bronchiolar lavage specimen from a SARS patient showed numerous coronavirus-infected cells with features similar to those in infected culture cells. Electron microscopic studies were critical in identifying the etiologic agent of the SARS outbreak and in guiding subsequent laboratory and epidemiologic investigations