252 research outputs found
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Plasmid Segregation: Is a Total Understanding Within Reach?
Recent in vitro and in vivo studies of the proteins responsible for the active partitioning of bacterial plasmids suggest that it will be possible to develop a quantitative, molecular understanding of this form of DNA segregation.Engineering and Applied SciencesMolecular and Cellular BiologyOther Research Uni
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Developing Cell Biology
Experiments in Xenopus embryo extracts reveal that changes in cellular biochemistry cause mitotic spindles to decrease in size over the course of early development.Molecular and Cellular Biolog
The physical basis of self-organization of the mammalian oocyte spindle
To prepare gametes with the appropriate number of chromosomes, mammalian
oocytes undergo two sequential cell divisions. During each division, a large,
long-lived, microtubule-based organelle called the meiotic spindle assembles
around condensed chromosomes. Although meiotic spindles have been intensively
studied for several decades, as force-generating mechanical objects, they
remain very poorly understood. In materials physics, coarse-grained theories
have been essential in understanding the large-scale behavior of systems
composed of many interacting particles. It is unclear, however, if this
approach can succeed in capturing the properties of active, biochemically
complex, living materials like the spindle. Here, we show that a class of
models based on nematic liquid crystal theory can describe important aspects of
the organelle-scale structure and dynamics of spindles in living mouse oocytes.
Using our models to interpret quantitative polarization microscopy data, we
measure for the first time material properties relating to stress propagation
in living oocytes, including the nematic diffusivities corresponding to splay
and bend deformations. Unlike the reconstituted amphibian spindles that were
previously studied in vitro, nematic elastic stress is exponentially screened
in the microtubule network of living mammalian oocytes, with a screening length
of order one micron. This observation can be explained by the relatively high
volume fraction of embedded chromosomes in mammalian meiotic spindles, which
cause long voids in the microtubule network and so disrupt orientational stress
propagation
A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation.
The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46-66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20-73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha-fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3-36 months) while that of the treated was 80 months (15-152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥ 151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV-associated HCC
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Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin
The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti–cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy. We found that autophosphorylation of the CPC decreases its sedimentation coefficient in egg cytosol and increases its diffusion coefficient in live cells, indicating a decrease in mass. Using immunoprecipitation coupled with mass spectrometry and immunoblots, we discovered that inactive, unphosphorylated CPC interacts with nucleophosmin/nucleoplasmin proteins, which are known to oligomerize into pentamers and decamers. Autophosphorylation of the CPC causes it to dissociate from nucleophosmin/nucleoplasmin. We propose that nucleophosmin/nucleoplasmin complexes serve as chaperones that negatively regulate the CPC and/or stabilize its inactive form, preventing CPC autophosphorylation and recruitment to chromatin and microtubules in mitosis
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